GM1 Ganglioside Effects on Parkinson's Disease

NCT ID: NCT00037830

Last Updated: 2012-12-21

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

94 participants

Study Classification

INTERVENTIONAL

Study Start Date

1999-11-30

Study Completion Date

2010-06-30

Brief Summary

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The purpose of this trial is to examine the short term effects (24 Weeks) of GM1 on Parkinson's disease (PD) symptoms, as well as the effects of long-term treatment (120 Weeks) with GM1 on disease progression, and to examine the extent to which GM1 treatment influences the underlying disease process in PD.

Detailed Description

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The study is designed to further examine the extent to which GM1 ganglioside can improve symptoms, delay disease progression, and, perhaps, partially restore damaged brain cells in PD patients. GM1 ganglioside is a chemical that is normally found in the brain and is a normal part of the outer covering or membrane of nerve cells. This study will compare the effectiveness of GM1 to standard PD treatment. In addition to studying clinical measures of motor and cognitive functioning, the investigators will use PET (positron emission tomography) scanning to image the brain and the dopamine nerve endings in a subgroup of patients. Patients with mild to moderate idiopathic PD will be divided into 2 groups. One group will receive GM1 for 24 weeks and the other will receive placebo. At the end of this 24 week period, all patients will enter into a 96 week treatment period in which all patients will receive GM1.

In parallel, a group of standard-of-care patients with mild to moderate PD will be monitored over a 1 to 2 year period to assess the natural progression of PD. These patients will receive the same clinical evaluations as the treatment group subjects but they will not receive the experimental medication.

Conditions

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Parkinson Disease

Keywords

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Parkinson's disease PD GM1 Ganglioside Sygen

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Early-Start Group

Subjects were randomized to receive GM1 ganglioside for 24 weeks.

Group Type ACTIVE_COMPARATOR

GM1 ganglioside

Intervention Type DRUG

100 mg twice per day by subcutaneous injection

Delayed-Start Group

Subjects were randomized to receive placebo for 24 weeks.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Twice per day subcutaneous injection, equal volume as active drug

Comparison Group

A separate group of Parkinson's disease patients who received standard of care were followed for one to two years to provide comparative information about natural disease progression. This comparison group was not compared statistically to the treatment groups since they were not randomized.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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GM1 ganglioside

100 mg twice per day by subcutaneous injection

Intervention Type DRUG

Placebo

Twice per day subcutaneous injection, equal volume as active drug

Intervention Type DRUG

Other Intervention Names

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Sygen

Eligibility Criteria

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Inclusion Criteria

* Btwn ages of 39-85 yrs old.
* Females: at least 2 years post-menopausal; surgically sterile; or negative pregnancy test by quantitative serum ßHCG, \& follow a reliable method of birth control for at least 2 months prior to entry, agree both to follow a reliable method of birth control, \& to desist from breast feeding during, \& for 1 month following, the study drug administration.
* Dx of idiopathic PD 6 months prior to screening. The diagnosis requires: the presence of at least 2 of the 4 cardinal clinical manifestations of the disease, tremor, rigidity, bradykinesia, and disturbances of posture or gait, \& at least 1 must be rigidity or bradykinesia.
* Modified Hoehn and Yahr Staging between 1 and 3 as rated during an "off" period of at least 12 hours.
* Unified Parkinson's Disease Rating Scale motor component score between 10 and 40 as rated during an "off" period of at least 12 hours and a score of 6 or greater during "on" period.
* Antiparkinsonian treatments: stable treatment of l-dopa/carbidopa and/or dopamine agonist for at least 3 months prior to Screening.
* Mini Mental State Exam score \> 25.
* Beck Depression Inventory score \< 10.
* Signed informed consent.

Exclusion Criteria

* Abrupt onset of Parkinsonism.
* Failure of Parkinsonian symptoms to have responded to l-dopa.
* Motor symptoms (such as peak dose dyskinesias (UPDRS score \> 3), \& random on-off phenomenon, other than end-of-dose wearing-off, persistently fluctuating over a 6 month or longer period, in response to l-dopa.
* Hx of findings of any movement disorder other than idiopathic PD.
* A tremor score on the UPDRS motor scale of \>5. Tremor score greater than 3 in an individual limb.
* High-dose vitamin E therapy (more than 1000 I.U./day) any time during the period starting 3 months prior baseline.
* Transient ischemic attack any time during the period starting 6 months prior baseline.
* Hx of 2 or more strokes. Hx of any stroke that resulted in motor deficit, movement disorder, ataxia, cognitive impairment, or a hemi-inattention syndrome. Any stroke with residua at the time of, or within 6 months preceding, study entry.
* Previous cerebral infarction, including lacunar infarction, in any area subserving motor function.
* Binswanger's disease or hx of hypertensive encephalopathy.
* Hx of encephalitis.
* Hx of extended exposure to any known neurotoxin that may cause parkinsonism, or chronic or sufficient use or consumption of any non-medicinal substance that could cause risk of developing a movement disorder or disturbance of posture or gait.
* Use of the following drugs within 6 months prior to screening: neuroleptics, metoclopramide, clozapine, flunarizine, alpha-methyldopa.
* Patients actively taking a medicine that is known to compete with the imaging agent for binding sites on the dopamine terminals.
* Hx of medication or drug use that may have caused atypical parkinsonism or history of Substance Use Disorder.
* Hx of a metabolic disorder that resulted or could have resulted in movement disorder or disturbance of posture or gait.
* Any disease or condition that resulted or could have resulted in a movement disorder or disturbance of posture or gait.
* Hx of intracranial hemorrhage, intracranial neoplasm, significant head trauma with loss of consciousness \>24 hrs or other structural brain disease.
* Hx or clinical findings suggestive of progressive supranuclear palsy or multiple system atrophy.
* Acquired cognitive impairment reasonably possibly due to any cause other than idiopathic PD.
* Hx of a hereditary disorder associated with a movement disorder.
* Normal or low pressure hydrocephalus.
* Any ill-defined neuropathic disease, myelopathy, myopathy or other medical disorder or physical condition by history or clinical examination that could be expected to interfere with the diagnosis, treatment or assessment of PD, or with any of the study assessments.
* Hx of Guillain-Barré syndrome, chronic idiopathic polyneuropathy, or relapsing polyneuropathy.
* Hx of Axis I or Axis II major psychiatric disorder.
* Significant cardiac, pulmonary, hepatic, gastrointestinal, or renal disease.
* Any condition that could alter the distribution, accumulation, metabolism, or excretion of the study medication; or result in a life expectancy of less than 2 years.
* Any primarily non-neurologic medical condition with a significant risk of secondarily causing neurologic dysfunction.
* Myocardial infarction within 6 months prior to screening.
* Presence of any medical condition or laboratory test abnormality or use of any licit or illicit substance which could cause unwarranted risk from participation in the study or result in worsening in the patient's medical condition during participation in study. Presence of any of the following laboratory test abnormalities are unwarranted risk: serum transaminase greater than twice the upper limit of normal;serum creatinine greater than 2.0 mg/dl in a man or greater than 1.7 mg/dl in a woman.
* Hx of a life-threatening allergic or immune-mediated reaction.
* Previous use of any ganglioside preparation.
* Use of any experimental drug in the period starting 60 days before Baseline.
* Hx of stereotaxic brain surgery for PD.
Minimum Eligible Age

39 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

Thomas Jefferson University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jay S. Schneider, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Parkinson's Disease Research Unit, Thomas Jefferson University

Locations

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Parkinson's Disease Research Unit, Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

Other Identifiers

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R01NS038681

Identifier Type: NIH

Identifier Source: secondary_id

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R01NS038681

Identifier Type: NIH

Identifier Source: org_study_id

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