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.
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.
- 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
- 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
- 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.
- 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
- 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
- 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
- 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
- Acquired cognitive impairment reasonably possibly due to any cause other than
- 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
- Hx of Guillain-Barré syndrome, chronic idiopathic polyneuropathy, or relapsing
- 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
- 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
- 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.