The goal of this study is to assess the impact of minocycline and creatine on the
progression of Parkinson's disease, in order to determine whether it is reasonable to
proceed with further study of either of these agents.
Parkinson's disease (PD) affects nearly a million Americans, a number that will increase
over the coming decades as the population ages. While available medical therapies are
usually effective for controlling symptoms in the initial years following diagnosis, higher
doses of multiple agents are required over time, with increasing side effects and incomplete
control of symptoms. Although these treatments can dramatically improve the lives of
patients with PD initially, they do not address the underlying causes of the disease or the
inevitable disease progression.
This multi-center, randomized, double-blind trial will involve 42 trial centers in the
United States and Canada, and enroll 195 people with PD. The primary objective of this
neuroprotection trial is to identify agents capable of slowing the progression of PD. In the
trial, investigators will assess the impact of minocycline and creatine on the progression
of PD and determine if it is futile or non-futile to proceed with further study of these
In this study, subjects with early, untreated PD will be equally randomized into one of the
three study arms: 1.) the group that receives active minocycline and placebo instead of
creatine, 2.) the group that receives active creatine and placebo instead of minocycline, or
3.) the group that receives placebo instead of minocycline and creatine. Subjects will
remain on the blinded study drug for 18 months.
- Willing and able to give informed consent.
- Men and women with idiopathic PD of less than 5 years duration from diagnosis.
- Diagnosis must be confirmed by bradykinesia plus one of the other cardinal signs
(resting tremor, rigidity) being present, without any other known or suspected cause
of parkinsonism. The clinical signs must be asymmetric.
- Subjects must not require any therapy (including levodopa, dopamine agonists,
anticholinergics, amantadine or selegiline) to treat symptoms of PD at the time of
enrollment. Subjects may have had prior exposure to any one of these agents, but
exposure with any agent may not have been longer than 60 days in duration and
subjects must not have been on any of these agents within 90 days prior to baseline.
Once a subject needs dopaminergic treatment, these medications may be added as part
of best medical management. The subject will still remain in the study.
- Age > 30 years.
- Willingness and ability to comply with study requirements.
- Women of childbearing potential (i.e., those not postmenopausal or surgically
sterile) may participate provided that they are using adequate birth control methods
for the duration of the study. Women of childbearing potential must have a negative
pregnancy test at baseline and be non-lactating.
- Use of any of the following drugs within 180 days prior to baseline: neuroleptics,
metoclopramide, alpha-methyldopa, clozapine, olanzapine and flunarizine.
- Use of any of the following drugs within 90 days prior to baseline: methylphenidate,
cinnarizine, reserpine, amphetamine or MAO-A inhibitors (pargyline, phenelzine, and
- Presence of atypical Parkinson's syndromes due to drugs (e.g., metoclopramide,
flunarazine), metabolic identified neurogenetic disorders (e.g., Wilson's disease),
encephalitis, or other degenerative diseases (e.g., progressive supranuclear palsy).
- Use of minocycline or creatine 90 days prior to baseline.
- Use of CoQ10> 300mg 90 days prior to baseline. Subjects must maintain a stable dosage
of CoQ10 throughout the duration of the trial.
- Participation in other drug studies or receipt of other investigational drugs within
90 days prior to baseline.
- Presence of freezing.
- Impairment of postural reflexes (pull test score >0).
- Any clinically significant medical condition (e.g., active GI illness, angina, active
neoplasm) or laboratory abnormality, which would in the the judgment of the
investigator interfere with the subjects ability to participate in the study or to be
- History of stereotaxic brain surgery for PD (e.g., pallidotomy, deep brain
stimulation, fetal tissue implantation).
- Clinically significant structural brain disease that the investigator believes would
interfere with study evaluations.
- History of known hypersensitivity or intolerability to minocycline or known allergy
to any tetracycline or creatine.