Clinical trial NCT00037830: GM1 Ganglioside Effects on Parkinson's Disease
Official title: The Study of GM1 Ganglioside, A Potential New Parkinson's Disease Medication
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Parkinson Disease
Keywords: Parkinson's disease
PD
GM1 Ganglioside
Sygen
Lead sponsor: Thomas Jefferson University
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2002-05-23
Enrollment: 94
Sex: ALL
Minimum age (years): 39
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Unified Parkinson's Disease Rating Scale (UPDRS) (Part III) Motor Score From Baseline to Week 24 Assessed Off Medication.
timeFrame: Baseline to Week 24
measure: Change in Unified Parkinson's Disease Rating Scale (UPDRS) (Part III) Motor Scores From Baseline to Week 120 Assessed Off Medication.
timeFrame: Baseline to Week 120
Secondary outcomes:
measure: Change From Baseline to Week 24 in Total Unified Parkinson's Disease Rating Scale (UPDRS)Score Assessed Off Medication
timeFrame: Baseline to Week 24
measure: Change in Total UPDRS Score From Baseline to Week 120 Assessed Off Medication
timeFrame: Baseline to Week 120
measure: Change in Unified Parkinson's Disease Rating Scale (UPDRS) (Part III) Motor Score From Baseline to Week 24 Assessed Off Medication.
timeFrame: Baseline to Week 24
measure: Change in Unified Parkinson's Disease Rating Scale (UPDRS) (Part III) Motor Score From Baseline to Week 48 Assessed Off Medication.
timeFrame: Baseline to Week 48
measure: Change in Unified Parkinson's Disease Rating Scale (UPDRS) (Part III) Motor Score From Baseline to Week 72 Assessed Off Medication.
timeFrame: Baseline to Week 72
measure: Change in Unified Parkinson's Disease Rating Scale (UPDRS) (Part III) Motor Score From Baseline to Week 96 Assessed Off Medication.
timeFrame: Baseline to Week 96
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Parkinson's Disease Research Unit, Thomas Jefferson University
state: Pennsylvania
Study officials:
affiliation: Parkinson's Disease Research Unit, Thomas Jefferson University
name: Jay S. Schneider, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: