Parkinson Study Group is your partner in clinical trials from start to finish. As North America's largest pro-active, not-for-profit scientific network of Parkinson Centers, we will provide optimal resources to assist you in planning, executing and dissemination of results. Learn more about our comprehensive services, superb track record and uncompromised reputation below.
Clinical Trials: Definition
TESTING OF EXPERIMENTAL DRUGS IN HUMANS
Before a medication can be sold over the counter or with a prescription, it must undergo rigorous testing. The process by which new medications are tested so they may ultimately be marketed to treat or cure various diseases or conditions is as follows:
Development of a Compound
Chemists in a laboratory develop compounds with a certain chemical structure that the scientists believe may function in humans to alleviate certain symptoms in a disease, or perhaps even cure it.
To prove that the compound works as is hypothesized and does not produce any negative side effects, it is first thoroughly tested in animals (e.g.., mice, rats, dogs, monkeys). This stage of testing is commonly referred to as the "pre-clinical" stage. The purpose of these animal studies is to prove that the drug is not carcinogenic (cancer causing), mutagenic (causing changes in the genetic material), or teratogenic (causing fetal malformations), and to understand how the drug is absorbed and excreted. Once a pharmaceutical company proves that the compound appears to be safe, and possibly effective in animals, the company will provide this information to the Food and Drug Administration (FDA) requesting approval to begin testing the compound (experimental drug) in humans via an Investigational New Drug (IND) application.
Clinical Trials/Studies in Humans
The clinical testing (investigation) of experimental drugs (previously unproven in humans, therefore "experimental") in humans is normally done in three phases (Phase I, II and III) with more and more people included in each subsequent phase. Although in general the phases are conducted sequentially, they may overlap. The three phases for testing experimental drugs are as follows:
Phase I Clinical Studies
Phase I studies are primarily concerned with the drug's safety, and are the first time the drug is tested in humans. These studies are typically done in a small number of healthy volunteers (20- 100), usually in a hospital setting where the volunteers can be closely watched and treated should there be any side effects. These volunteers are usually paid for their participation and for the most part tend to be men (approximately 30 years of age on average). The purpose of these studies is to determine how the experimental drug works in humans. That is, how is the drug absorbed, metabolized, and excreted. Additionally, they seek to determine what types of side effects occur as the dosage levels (that is, the amount of drug) are increased, as well as to obtain early evidence on drug effectiveness.
The PSG has not been involved in Phase I testing. However, it is during Phase I testing that the PSG is collaborating with the pharmaceutical company to plan Phase II and III clinical trials in Parkinson's disease.
Phase II Clinical Studies
Once an experimental drug has been proven to be safe and well tolerated in healthy volunteers, it must be tested in the patients that have the disease or condition that the experimental drug is expected to improve/cure. In addition to ensuring that the experimental drug is safe and effective in the patient population of interest, Phase II studies are also designed to evaluate the effectiveness of the drug. The second phase of testing may last from several months to a few years and up to several hundred patients. Most Phase II studies are well controlled, randomized trials. That is, one group of patients (subjects) will receive the experimental drug, while a second "control" group will receive a standard treatment or placebo. Placement of the subject into the drug treatment or placebo group is by random chance (as if by the flip of a coin). Often these studies are "double-blinded", that is, the patient nor the researchers (investigator, coordinator, etc.) know who is getting the experimental drug. Additionally, Phase II studies are often designed to determine the correct dosage, that is the dosage with the least number of side effects that is most effective. These are often referred to as dose-ranging studies. In general, the purpose of Phase II studies is to provide the pharmaceutical company and the FDA comparative information about the relative safety of the experimental drug, the proper dosage, and the drug's effectiveness. Only about one-third of experimental drugs successfully complete both Phase I and Phase II studies.
The PSG has been heavily involved in the Phase II testing of numerous experimental drugs for PD. Many of these experimental drugs moved into Phase III testing and were ultimately approved by the FDA for use in PD.
Phase III Clinical Studies
In a Phase III study, an experimental drug is tested in several hundred to several thousand patients with the disease/condition of interest. Most Phase III studies continue to be randomized and blinded. The large-scale testing provides the pharmaceutical company as well as the FDA with a more thorough understanding of the drug's effectiveness, benefits/risks, and range/severity of possible adverse side effects.
Phase III studies typically last several years. Seventy to 90 percent of drugs that enter Phase III studies successfully complete this phase of testing.
Marketing of New Drugs
After successful completion of Phase I-III testing, a company will submit the results of all of the studies to the FDA to obtain a New Drug Application (NDA). Once the FDA grants a company with a NDA, the company can market the drug (medication) to the public. Additional testing (post-marketing or late phase III/phase IV) to look at the long-term safety continues.
What about Natural Remedies?
Patients are often interested in natural treatments of Parkinson's disease. It is important to understand that "natural" products are not subjected to the kind of rigorous testing outlined above. Therefore data are not always available for the safety or effectiveness of these treatments.
Study Budget Committee
The Study Budget Committee, as described in the PSG Policies & Procedures, is responsible for developing site and “per subject fee” costs for study budget proposal purposes. The Committee will be responsible for providing uniform site and “per-subject-fee” budgetary input for all PSG projects. Costs shall be representative of the needs of the majority of PSG sites. The Committee will also be the focal point for considering changing and newly emergent issues related to site compensatory issues and shall make recommendations on site budgetary issues to the PSG Executive Committee.
For all PSG studies, a budget must be formulated that includes elements to cover site costs for the evaluation of study participants (the “per-subject fee”, PSF). A long-standing principle of the PSG is to develop a uniform rate for site payment and the PSF. It is desirable for the PSF to reflect a rate that will allow for fair compensation to sites such that the decision of a site to participate is not unduly influenced by compensation issues. Indirect rates vary by institution and PI’s need to take this into consideration. All PIs are required to obtain Study Budget Committee review prior to submitting their budget to the proposed sponsor.
Composition of the Study Budget Committee:
- The PSG Executive Committee will appoint 3 investigator and 3 coordinator PSG members for 3 year terms.
- One of the members is appointed the Committee Chair, who is responsible for organizing and representing the consensus of the group. The Committee may seek advice from people not on the committee from time-to-time.
- The PSG Administrative Manager provides the study PI with historical PSF’s, broken down by activity (eg vital signs), indicating more recent PSFs.
- The PI chooses an appropriate cost per activity based on past PSFs and his/her expertise and judgment. A total PSF is constructed from the individual items.
- The PSG Administrative Manager emails the protocol synopsis, schedule of activities and Excel budget page to the Committee requesting comments on the budget proposal.
- The Committee chair asks Committee members to forward their review of the proposed PSF and condenses their comments.
- The Committee chair communicates the comments to the PI, who has final authority to set the PSF.
- Efficiency in the development of the PSF
- Explicit process known to the PSG membership Committee participation promotes learning and improves consistency in PSF preparation
- Provides Study PI with a consensus-driven PSF justification during negotiation with sponsors.
Featured link: Fox Trial Finder, a resource of the Michael J. Fox Foundation
Clinical Trials in Progress
NILO-PD: A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Define the Safety, Tolerability of Nilotinib in Participants with Parkinson’s Disease (PD)
The Parkinson Study Group (PSG), under the direction of Tanya Simuni, MD (Northwestern University) is conducting a multi-center, randomized, double-blind, placebo-controlled study of nilotinib in individuals with moderate to advanced Parkinson’s disease (PD). Nilotinib is approved by The Food and Drug Administration (FDA) for certain types of leukemia but not for PD. To date, the safety and tolerability of nilotinib in the PD and Dementia with Lewy Bodies populations have only been studied in a single small open label clinical study (Pagan et al. 2016).
The purpose of the NILO-PD study is to determine if nilotinib is safe, if it can be tolerated by patients with PD and to learn if nilotinib has the possibility of effectively treating PD symptoms. Twenty-five sites will enroll participants into 2 cohorts, approximately 75 in Cohort 1 and 60 in Cohort 2. Participants with moderate to advanced PD symptoms will be enrolled in Cohort 1, randomly assigned to take nilotinib (150 mg or 300mg) or placebo, and will complete 13 in-person study visits over 8.5 months. Cohort 1 Participants need to be on a stable regimen of PD medications, that includes levodopa, for at least 30 days prior to the screening visit. The results from Cohort 1 will determine if either dose of nilotinib (150mg or 300 mg) is safe and tolerable enough to move forward and evaluate in Cohort 2. If either dose is found to be safe and tolerable, participants with early PD will be enrolled into Cohort 2.
NILO-PD is being conducted under a research grant award from the Michael J. Fox Foundation for Parkinson’s Research. For contact information on participating sites in this study, click here.
Pagan F, Hebron M, Valadez EH, et al. Nilotinib Effects in Parkinson's disease and Dementia with Lewy bodies. J Parkinsons Dis. 2016.
SPARK (A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Pharmacokinetics, and Pharmacodynamics of BIIB054 in Subjects with Parkinson's Disease)
This study is not yet open for participant recruitment.
The Parkinson Study Group (PSG) is conducting, under the direction of Andrew Siderowf, MD, a Phase 2a, randomized, double-blind, placebo-controlled trial to to evaluate the dose-related safety of BIIB054, to evaluate the pharmacodynamic effects of BIIB054 on the integrity of nigrostriatal dopaminergic nerve terminals, to assess the pharmacokinetic (PK) profile of BIIB054 and to evaluate the immunogenicity of BIIB054 in subjects with Parkinson’s disease.
The trial is funded by Biogen and registered on clinicaltrials.gov (NCT03318523).
SURE-PD3 (A Phase 3, Randomized, Double-blind, Placebo-controlled Trial of Urate-elevating Inosine Treatment to Slow Clinical Decline in Early PD)
The Parkinson Study Group (PSG) is conducting, under the direction of Michael Schwarzschild, MD PhD, a placebo-controlled, randomized, double-blind study to assess the disease-modifying potential of the drug inosine in people with early stage Parkinson’s disease (PD).
Epidemiological and laboratory studies provide evidence that raising levels of the endogenous antioxidant and purine metabolite urate may slow the the development and progression of Parkinson’s disease. This trial is unique in that it aims to explore a drug with possible neuroprotective effects that may combat the progression of early PD instead of the severity of its symptoms. A phase 2 study of the urate precursor inosine indicated its ability to safely elevate urate in serum and cerebrospinal fluid when administered orally over months to years in people with early Parkinson’s.
The SURE-PD3 study seeks to screen some 670 subjects with probable early PD at 60 clinical sites located across the US to identify 270 subjects with serum urate ≤5.7 mg/dL and a dopamine transporter brain scan supportive of PD. They will be randomized 1:1 to receive oral inosine or placebo for two years. Inosine dosing will be titrated to achieve moderately elevated serum urate (7.1-8.0 mg/dL). Subjects will be monitored using the study’s primary outcome measure, the MDS-UPDRS as well as multiple other safety and secondary clinical assessments. The PSG, Massachusetts General Hospital and University of Rochester share responsibility for the design and execution of the study.
Interested individuals with early PD (< 3 years since diagnosis) and that are not yet required to take dopaminergic medication (except that monoamine oxidase-B inhibitors are allowed) may be eligible in the SURE-PD3 trial. Additional information can be obtained via clinical trial websites of the US National Institutes of Health (NIH) here, The Michael J. Fox Foundation here, or the National Institute of Neurological Disorders and Stroke (NINDS) here. Subjects will receive a reimbursement for expenses for visits on study drug. A short video introducing SURE-PD3 may be viewed here.
The trial is funded by NIH/NINDS. Additional support is provided by the Michael J. Fox Foundation (including for a biomarker blood collection sub-study) and from the Parkinson’s Foundation with the contributions of its Parkinson’s Advocates in Research (PAIR) program featured here).
SYNAPSE: (SYN120 a Dual 5-HT6/5-HT2A Antagonist Proof of Concept Study to Evaluate Its Safety, Tolerability and Efficacy in Parkinson's Disease Dementia)
Active, not recruiting
The Parkinson Study Group (PSG), under the direction of the SYNAPSE Steering Committee, is conducting a placebo-controlled, randomized, double-blind study to assess the safety and efficacy of SYN120 in patients with Parkinson's disease dementia (PDD) already treated with a stable dose of a cholinesterase inhibitor.
SYN120 is an orally administered antagonist of the serotonin 5-HT6 receptor in development for the treatment of cognitive disorders, including dementia associated with Parkinson’s disease. 5-HT6 receptors are located almost exclusively in the brain and blocking them results in increased concentrations of acetylcholine and glutamate, two neurotransmitters known to facilitate cognition. In addition to blocking the 5-HT6 receptor, SYN120 also antagonizes 5-HT2a receptors, an action that may help treat psychosis associated with Parkinson’s disease. Thus SYN120 offers a unique therapeutic strategy by combining its procognitive and antipsychotic potential.
The SYNAPSE study randomized 1:1 eighty-two patients with PDD and on a stable dose of an acetylcholinesterase inhibitor to placebo or SYN120 dosed once daily over a 16 week treatment period. In addition to assessing safety and tolerability, the main goal of the study is to establish efficacy of SYN120 on cognition using the Cognitive Drug Research (CDR) Computerized Cognition Battery as the primary efficacy endpoint. The study will be conducted at approximately 20 PSG sites in the United States specializing in cognitive dysfunction in Parkinson's disease. Biotie and the PSG share responsibility for the design and execution of the study, and initial results of the study are expected in by the beginning of 2018.
There is no cost to participate in SYNAPSE. Interested individuals with PDD may obtain more information regarding this trial via its entries on clinical trial websites of the US National Institutes of Health here, or The Michael J. Fox Trial Finder website here.
Read the Biotie announcement of the SYNAPSE study here.
STEADY-PD III: Efficacy of Isradipine in early Parkinson Disease
Enrollment is complete.
The Parkinson Study Group (PSG), under the direction of Tanya Simuni, MD (Northwestern University), and Robert G. Holloway, MD, MPH (University of Rochester), is conducting a multi-center, randomized, double-blind, placebo-controlled study of isradipine in individuals with early Parkinson disease (PD) called STEADY-PD III. The purpose of STEADY-PD III is to assess the potential effect of isradipine on slowing the progression of PD. Approximately 56 research centers across North America will enroll up to 336 subjects.
Isradipine is a medication that is approved for the treatment of high blood pressure by the Food and Drug Administration Agency (FDA), but not for the treatment of PD. Isradipine has been shown to have a neuroprotective effect in preclinical models of parkinsonism (Chan, Guzman et al. 2007). A recently completed Phase II study funded by the MJFF in a PD population demonstrated that isradipine is safe and well tolerated up to the dose of 10 mg (2013).
STEADY-PD III is being conducted under a research grant award from the National Institute of Neurological Disorders and Stroke.
For contact information on participating sites in this study, click here or call 1-855-825-3390 or 1-855-825-3390.
(2013). "Phase II safety, tolerability, and dose selection study of isradipine as a potential disease-modifying intervention in early Parkinson's disease (STEADY-PD)." Mov Disord.
Chan, C. S., et al. (2007). "'Rejuvenation' protects neurons in mouse models of Parkinson's disease." Nature 447(7148): 1081-1086.
Completed Clinical Trials & Completed Trials – Analysis/Publication Phase
Completed Clinical Trials
The BLIND-DATE trial ("BLINDed Withdrawal of Deprenyl in the DATATOP Extension") examined the long-term effects of deprenyl on the course of levodopa-treated Parkinson's disease. (See DATATOP in the Completed Clinical Trials section for the background and details of BLIND-DATE).
The PSG, under the sponsorship of Pharmacia & Upjohn, Inc. (Kalamazoo, MI), led by Ira Shoulson, MD, and Stanley Fahn, MD, conducted the study, CALM-PD (Comparison of the Agonist Pramipexole versus Levodopa on Motor Complications of Parkinson's Disease). Enrollment of 301 subjects at 22 sites began in October 1996 and was completed August 1997. This parallel group, double-blind controlled trial is designed to compare the policies of initial treatment with pramipexole versus initial treatment with carbidopa/levodopa in Parkinson's disease patients. The development of dopaminergic motor complications was the primary outcome of interest. This study also included ß-CIT SPECT measurements, an economic outcome substudy, and a quality-of-life instrument customized for Parkinson's disease. Subjects were examined prospectively for at least 23.5 months, after which time they had the option of participating in the blinded extension of CALM-PD. Subjects concluded participation in CALMPD and its extension in August, 2001. The results of the CALM-PD study were published in JAMA on October 18, 2000.
DARE (Dyskinesias And Remacemide Effects), led by Anthony Lang, MD, Stanley Fahn, MD and Ira Shoulson, MD, and sponsored by Astra Pharmaceuticals, was a placebo-controlled study of subjects with Parkinson's disease who have severe dyskinesias despite optimized antiparkinsonian medications. Enrollment of 39 subjects at five sites began in December 1997 and was completed in May 1998. A report summarizing the preliminary data from RAMP, REAL and DARE entitled "The Glutamate Antagonist Remacemide Improves Motor Performance in Levodopa-Treated Parkinson's Disease" was presented at the 51st Annual Meeting of the American Academy of Neurology Scientific Session, April 21, 1999, in Toronto, Canada.
DATATOP AND ITS FOLLOW-ON PROTOCOLS
DATATOP (Deprenyl And Tocopherol Antioxidative Therapy Of Parkinsonism), led by Ira Shoulson, MD, and Stanley Fahn, MD, and sponsored by NINDS, is the largest and longest prospective controlled study of therapeutic interventions in Parkinson's disease conducted in the world. It was the first of PSG's multi-center trials. *(Click here to download the complete PDF.)
Evaluation of DOPASCAN™ in Parkinson's Disease and Related Disorders
PSG, under the leadership of Kenneth Marek, MD, and John Seibyl, MD, and the sponsorship of Guilford Pharmaceuticals, Inc. (Baltimore, MD), conducted a five-center trial to examine DOPASCAN™, a SPECT imaging ligand, as a diagnostic marker for Parkinson's disease. DOPASCAN™ is a radiotracer that binds to the dopamine transporter and provides a measure of the integrity of dopamine terminals. Enrollment and follow-up of 96 subjects at five sites was completed in December 1996. Data were published in abstract form in Movement Disorders and Journal of Nuclear Medicine and a full report is under review.
One of the most lingering and important questions in the therapeutics of PD is whether levodopa, the mainstay of treatment, has long-term beneficial or harmful effects on the progression of disease. A survey on treating patterns was conducted during the PSG/MDS Symposia in October 1995 and reported in October 1996 in Movement Disorders. An application was submitted to the National Institute of Health (NIH) in June 1996 for the ELLDOPA (Earlier versus Later LevoDOPA) placebo-controlled trial, which was reviewed favorably and awarded by the National Institute of Neurological Disorders and Stroke (NINDS-NIH) in January 1998. The ELLDOPA trial, under the direction of Stanley Fahn, MD, and Ira Shoulson, MD, began enrollment of 360 patients with early Parkinson's disease at 35 PSG sites in October 1998. Subjects were followed for 40 weeks prior to a 17-day washout and final evaluation of the progression of disease. A ß-CIT SPECT study, funded by a grant to Kenneth Marek, MD, by the Department of Defense, was carried out in a sub-set of ELLDOPA subjects to assess a biological marker of the progression of Parkinson's disease (loss of dopamine transporter binding sites). As of September 2001, enrollment was closed for the study with 361 subjects completing enrollment. The final subject visit is expected in June 2002 with analysis to follow. For additional information on the scientific rationale for this study, please see the 1999 publication in Archives of Neurology.
MOVE-PD (A Phase II Study to Evaluate the Safety and Efficacy of RM-131 in Patients With Parkinson's Disease & Chronic Constipation)
Status, January 18, 2017: Primary paper submitted to Parkinsonism and Related Disorders journal.
The Parkinson Study Group (PSG), under the direction of the MOVE-PD Steering Committee, conducted a clinical trial to test a new treatment for chronic constipation among Parkinson’s disease (PD) patients. Constipation is a common non-motor symptom of PD, which can cause extreme discomfort.
Researchers investigated how individuals with PD and chronic constipation respond to the drug RM-131, as compared to placebo. The study was originally sponsored by Rhythm Pharmaceuticals, Inc. (Boston, Massachusetts) with funding provided by The Michael J. Fox Foundation for Parkinson’s Research. PI: Ronald F. Pfeiffer, M.D.
For more information regarding this trial visit clinicaltrials.gov.
NIC-PD (A Randomized, Placebo-controlled, Double-blind, Multi-centre Trial to Assess the Disease-modifying Potential of Transdermal NICotine in Early Parkinson's Disease) in Germany and the USA.
Status, January 18, 2017: Analysis Phase
The Parkinson Study Group (PSG), under the direction of Wolfgang Oertel, MD (Philipps University, Marburg Germany), and James Boyd, MD (University of Vermont), conducted a randomized, placebo-controlled, double-blind, multi-center trial to assess the disease-modifying potential of transdermal nicotine in early Parkinson's disease in Germany and the USA. The purpose of the study was to demonstrate that transdermal nicotine treatment retards disease progression as measured by change in the Unified Parkinson's Disease Rating Scale (UPDRS) (part I, II, III) score between baseline and after 52 weeks of study treatment plus two more months following a wash-out period (60 weeks). Approximately 20 research centers in the United States and Germany enrolled approximately 160 subjects for 12 months each.
The nicotine transdermal patch is a medication that is approved as a smoking cessation aide by the Food and Drug Administration Agency (FDA), but not for the treatment of PD. Up to now no drugs are available that can delay or halt the progression of Parkinson’s disease. Nicotine is a promising substance for this purpose for several reasons. PD is much less prevalent among smokers compared to never-smokers. Over 40 independent epidemiological studies suggest a protective effect cigarette smoking against development of PD, and this effect is suspected to be caused by nicotine. In experimental neuroscience, including research using several PD animal models, nicotine has shown to protect against the loss of the dopamine-producing cells lost in PD. Additionally, the drug is widely available and exhibits a favorable safety profile.
This study was conducted under two research grant awards from The Michael J. Fox Foundation one to Philipps University, Marburg, Germany and the other to the University of Rochester, Rochester, New York.
If you are interested in learning more about this study, please see the study on www.clinicaltrials.gov
PATCH I (PArkinson's Disease Transdermal Clinical Trial Helping to Assess SPM-962 Transdermal System (TDS) in Patients Not Receiving DopaminergicTherapy), led by Ira Shoulson, MD, and under the sponsorship of Schwarz Pharma Inc. (Meguon, WI and Monheim, Germany) conducted a Phase IIb efficacy, safety and tolerability study of the experimental dopamine agonist SPM-962, delivered as a transdermal patch system in patients with Parkinson's disease who are not receiving dopaminergic therapy. Enrollment of 242 subjects at 28 sites began on November 15, 1999 and was completed in July, 2000.
The Parkinson Study Group (PSG), in collaboration with two pharmaceutical companies, Cephalon, Inc. (West Chester, PA) and H. Lundbeck A/S (Valby-Copenhagen, Denmark), conducted a study for patients with early Parkinson's disease called PRECEPT (Parkinson Research Examination of CEP1348 Trial). The goal of PRECEPT was to determine if the investigational drug CEP-1347 could slow the clinical progression of early Parkinson's disease. The study assessed the safety and tolerability of different doses of CEP-1347 and also examined the long-term effects of CEP-1347 on the areas of the brain affected by Parkinson's disease. The study recruited approximately 800 participants at 65 sites across the United States and Canada. Enrollment began in April 2002 and was completed in March 2004.
The Parkinson Study Group (PSG), in collaboration with Teva Clinical Research, Inc., conducted a study for patients with moderate to advanced Parkinson’s Disease called PRESTO (Parkinson's Resagiline: Efficacy & Safety in the Treatment of "Off"). This 26-week study examined the safety, effectiveness and tolerability of an investigational drug in patients who do not experience full benefit from their L-dopa dosage. The study recruited about 450 subjects at 44 sites across the United States and Canada. Enrollment began in September 2000 and was completed in June 2002.
The PRIME (PRamipexole In Minority Persons with Parkinson's Disease: Efficacy) study led by Caroline Tanner, MD, and Cynthia Comella, MD, and sponsored by Pharmacia & Upjohn, Inc. (Kalamazoo, MI) was a placebo-controlled, safety, efficacy and pharmacokinetic study of pramipexole in minority persons with moderate to advanced Parkinson's disease who are receiving concomitant carbidopa/levodopa therapy. Enrollment of 144 subjects at 17 sites began in January 1997 and the final subject visit was completed in October 1998. This is the first trial in Parkinson's disease designed to evaluate the influence of ethnicity on the safety, efficacy and pharmacokinetics of a therapeutic agent.
The PSYCLOPS (PSYchosis and CLOzapine in Parkinson'S Disease) study led by Joseph Friedman, MD, and Christopher Goetz, MD, which examined the effects of the non-neuroleptic, antipsychotic clozapine on dopaminergic-induced psychosis in PD patients, was supported primarily by the FDA Orphan Drug Division. Enrollment of 60 subjects at six PSG sites began in April of 1995 and the final subject visit was completed in January 1997. This randomized, controlled clinical trial supported the findings of multiple open-label studies that low dose clozapine ameliorates psychosis without worsening parkinsonism. The results have been published in abstract form and a full report was in the March 1999 issue of the New England Journal of Medicine, volume 340, pg 757-763.
QE2 (Coenzyme Q10 Evaluation-2) was a randomized, double-blind, parallel group 16-month study, designed to compare three dosages of coenzyme Q10 (ubiquinone) and placebo in patients who have early PD. Ten PSG sites were selected to enroll 80 subjects. The goals of the study were to: (1) assess a clinical trial design devised to efficiently evaluate the maximally tolerated dose and efficacy of potential protective therapies for PD; (2) extend our previous studies of the safety and tolerability of high doses of coenzyme Q10; and (3) evaluate the ability of coenzyme Q10 to affect the clinical progression of PD and platelet mitochondrial function. Enrollment of 80 subjects was completed in February of 2000.
Quality-of-Life Instrument/Economic Outcomes (PDQUALIF)
Parkinson's Disease QUAlity of LIFe (PDQUALIF) was a multi-center study to develop and test a quality-of-life instrument specific for Parkinson's disease. Under the direction of Mickie Welsh, RN, DNS, this study employed a cross-sectional design of individuals in all stages of Parkinson's disease in an effort to establish the reliability and validity of the PDQUALIF. There were a total of 233 patients enrolled at the participating 13 PSG sites. Analysis compared the PDQUALIF to the SF36 and SIP quality-of-life instruments. An abstract of the preliminary results from Phase II testing was presented at the 1997 PSG/Movement Disorders Society (MDS) Symposia and published in Movement Disorders. In the CALM-PD and TEMPO trials, a modified PDQUALIF scale was used.
The RAMP (Remacemide As Monotherapy in Parkinson's Disease) study, led by Ira Shoulson, MD, and J. Timothy Greenamyre, MD, PhD, and sponsored by Astra Pharmaceuticals was the first placebo-controlled study to evaluate the safety, tolerability and efficacy of dosages of remacemide as monotherapy in patients with early Parkinson's disease. Enrollment of 200 subjects at 21 PSG sites began in March 1997 and was completed in April 1998.
The Parkinson Study Group (PSG), under the sponsorship of Teva Clinical Research, conduced a study for advanced Parkinson's disease patients with motor complications ("on-off" effects) called RAPID (Rapid-Acting ParkInson's Drug). This 20-24 week study of TV-1203/Carbidopa dispersible tablets, a novel investigational variation of levodopa, examined the efficacy, safety, and tolerability of TV-1203/Carbidopa dispersible tablets in treating advanced Parkinson disease patients who have motor fluctuations while being treated with chronic levodopa/carbidopa therapy. Teva Clinical Research, based in North Wales, PA is the U.S. affiliate of Teva Pharmaceutical Industries, LTD, Israel, an international pharmaceutical company headquartered in Israel. This study enrolled approximately 300 patients at 41 sites across the United States and Canada and completed enrollment in June 2002.
REAL (REmacemide as an Adjunct to Levodopa), led by Ira Shoulson, MD, and John Penney, MD, and sponsored by Astra Pharmaceuticals, was the first placebo-controlled study to evaluate the safety, tolerability and efficacy of remacemide in levodopa-treated patients with Parkinson's disease who have motor fluctuations. Enrollment of 279 subjects at 29 PSG sites began in August 1997 and was completed in June 1998.
Follow-up of the 320 subjects in the ROADS (RO 19-6327 Assessment and Dose Finding Study) controlled trial of the MAO-B inhibitor lazabemide, led by Ira Shoulson, MD, and Karl Kieburtz, MD, was completed in 1994 and analysis was completed in 1995. Like deprenyl, lazabemide extended the time before emerging disability required the initiation of levodopa therapy in patients with early Parkinson's disease. An abstract of the preliminary results of this 18-site investigation of lazabemide in untreated PD patients was presented in May 1995 at the annual meeting of the American Academy of Neurology. A full report was published in Annals of Neurology.
The SEESAW (Safety and Efficacy of Entacapone Study Assessing Wearing-off) controlled trial, led by Ira Shoulson, MD, and Stanley Fahn, MD, and sponsored by Orion-Farmos, Inc. (Espoo, Finland), was initiated in March 1994 to examine the impact of entacapone, a COMT inhibitor, in levodopa-treated PD patients with motor fluctuations. Enrollment of 205 subjects at 18 PSG sites was completed in December 1994, and follow-up was completed in June 1995. A summary of the results of the study was presented at the Fourth International Congress of Movement Disorders meeting in Vienna, Austria, June 1996 (published in Movement Disorders) and the 10th PSG/MDS Symposia in Miami, October 1996 (published in Movement Disorders). A full report of the SEESAW trial was published in Annals of Neurology.
The PSG study, led by Karl Kieburtz, MD, and John Nutt, MD, and sponsored by Astra Pharmaceuticals, conducted the study SPIRAL (Study of Pharmacokinetic Interactions Between Remacemide And Levodopa), which was the first study to evaluate whether remacemide, a glutamate receptor antagonist, exerts an effect on circulating plasma levodopa concentrations in patients with Parkinson's disease. Enrollment of 16 subjects at four sites began in February 1997 and was completed in April 1997. A report has been submitted for publication.
START-LE (Short Term Assessment of RO 19-6327 Tolerability in Levodopa Exposed Patients) was the second of the PSG's trials investigating lazabemide. In this trial, sponsored by Hoffmann-La Roche and led by Ira Shoulson, MD, and Stanley Fahn, MD, 137 subjects being treated with levodopa for their Parkinson's disease were enrolled at 14 sites from March 1991 to January 1992. This eight-week study demonstrated the overall safety and tolerability of lazabemide in subjects taking levodopa. The primary report of this study was published in Archives of Neurology.
Lazabemide (RO 19-6327) is a short-acting, reversible, highly selective inhibitor of monoamine oxidase type B which, unlike deprenyl, is not metabolized to active compounds. The PSG, under the sponsorship of Hoffmann-La Roche, Inc. (Nutley, NJ), and led by Ira Shoulson, MD, and Stanley Fahn, MD, undertook the first of its three trials of lazabemide in the study START-UP (Short Term Assessment of RO 19-6327 Tolerability in Untreated Parkinson's Disease) from November 1990 to September 1991; 201 subjects with early, untreated PD were enrolled at 14 sites. The overall safety and benefits of lazabemide observed in this eight-week trial justified further long-term investigation of the drug. The primary report of the study was published in Annals of Neurology.
Phase II Safety, Tolerability, and Dose Selection Study of Isradipine as a Potential Disease-Modifying Intervention in Early Parkinson’s Disease (STEADY-PD) was undertaken in subjects with early PD not requiring dopaminergic therapy (dopamine agonists or levodopa) randomized 1:1:1:1 to 5, 10, or 20 mg of isradipine CR or matching placebo daily. The primary outcome was tolerability defined as no more than a 30% difference in the proportion of patients completing the study on the originally assigned dosage between an active and placebo group. If more than one isradipine dosage was tolerable, then a 3-point difference in total Unified Parkinson’s Disease Rating Scale (UPDRS) change between baseline and week 52 (or time to sufficient disability to require dopaminergic therapy) was taken as a criterion for selection of the most desirable dosage for future study. STEADY-PD enrolled 99 subjects. The tolerability of isradipine was dose dependent: placebo, 25 of 26 patients (96%); 5 mg, 19 of 23 patients (83%); 10 mg 19 of 26 patients (73%); and 20 mg 9 of 24 patients (37%). There was no difference in change in UPDRS among dosages. The most common adverse events were peripheral edema (30) and dizziness (24). Isradipine 10 mg daily was the maximal tolerable dosage in this study of early PD. A large placebo-controlled trial will be necessary and is planned to assess efficacy of isradipine 10 mg daily to slow progression of PD disability. *(Click here to download the complete abstract.)
The STEP-UP (Safety, Tolerability and Efficacy of Pramipexole in Untreated Parkinsonism) controlled trial, led by Ira Shoulson, MD, and Stanley Fahn, MD, and sponsored by Pharmacia & Upjohn, Inc., was initiated in March 1994 to examine multiple dosages of the dopamine agonist pramipexole in early PD. Active follow-up of the 264 enrolled subjects at 20 PSG sites was completed in December 1994. An abstract summarizing the preliminary results of this trial was presented at the PSG/MDS Symposia in Washington, DC, October 1995, and published in Movement Disorders. A full report of the STEP-UP trial was published in the July 9, 1997 issue of the Journal of the American Medical Association.
TEMPO (Rasagiline Mesylate [TVP-1012] in Early Monotherapy for PD Outpatients), led by Ira Shoulson, MD, and Stanley Fahn, MD, is a placebo-controlled multi-center trial, sponsored by Teva Pharmaceutical Industries, Ltd. – Israel and Teva Pharmaceuticals, USA, examining the effects of two dosages of rasagiline in patients with early Parkinson's disease. Rasagiline is a novel MAO-B inhibitor. Enrollment of approximately 400 patients at 27 PSG sites began in November 1997 and was completed in April of 1999. The results of the TEMPO study were published in Archives of Neurology on December 18, 2002.
The TEST-PD/RETEST-PD (Tolerability and Efficacy of SIB-1508Y Therapy in PD), led by Ira Shoulson, MD and John Growdon, MD, and sponsored by SIBIA Neurosciences, Inc. (La Jolla, CA), is the first placebo-controlled study to evaluate the safety, tolerability and efficacy of dosages of SIB-1508Y in patients with Parkinson's disease who are requiring, but not receiving, dopaminergic therapy. SIB-1508Y is a nicotinic acetylcholine receptor agonist which produces motor and cognitive benefits in animal models of Parkinson's disease. Enrollment of 32 subjects at ten sites for the initial phase of the study (TEST-PD, higher dosage groups) began in January 1998 and was completed in May, 1998. Enrollment of 45 subjects for the second phase (RETEST-PD, lower dosage groups) began in July 1998 and was completed in April 1999. The data are currently being analyzed.
Completed Studies – Analysis/Publication Phase in Process
Click on any title to view the trial record at ClinicalTrials.gov.
(Parkinson’s Disease On EsTrogen Replacement in the Menopause Years)
(A randomized, double-blind, active (pramipexole 0.5 mg tid) and placebo controlled, efficacy study of pramipexole, given 0.5 mg and 0.75 mg bid over a 12-week treatment phase in early PD patients)
Diagnostic and Prognostic Biomarkers in Parkinson Disease
(Parkinson’s Research: The Organized GENetics Initiative)
(Effects of Coenzyme Q10 in Parkinson Disease)
March 24, 2014
The primary manuscript for QE3 was accepted and has been published in JAMA Neurology. The abstract and manuscript can be viewed here.
July 27, 2012
The QE3 study was presented at the 16th International Congress of Parkinson's Disease and Movement Disorders Meeting in Dublin, Ireland in June 2012. An abstract, or a short summary of study results, was presented at the meeting and a copy of the material is available here.
May 27, 2011
The NINDS has stopped the QE3 Phase III study of Coenzyme Q10 for treatment of early Parkinson’s disease acting on the recommendation of the study’s Data Safety Monitoring Board (DSMB).
(SPectroscopy IN Diagnosis of PD)
(Safety and Ability to Elevate URate in Early Parkinson Disease)