Study of Rifampicin in Multiple System Atrophy
Information source: Mayo Clinic
Information obtained from ClinicalTrials.gov on December 08, 2011
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Multiple System Atrophy
Intervention: Rifampicin (Drug); placebo (Drug)
Phase: Phase 3
Sponsored by: Mayo Clinic
Official(s) and/or principal investigator(s):
Phillip A Low, MD, Principal Investigator, Affiliation: Mayo Clinic
David Robertson, MD, Principal Investigator, Affiliation: Vanderbilt University
Sid Gilman, MD, Principal Investigator, Affiliation: University of Michigan
The purpose of this study is to determine whether Rifampicin is effective in slowing or
reversing the progression of multiple system atrophy (MSA). Research studies indicate that
there is an abnormality in protein synthesis and structure in parts of the brain responsible
for MSA (protein misfolding) and the drug Rifampicin could potentially prevent or reverse
this protein alteration. The study will be done on participants with early MSA. The study
will consist of taking the drug 2 times a day for 12 months. Participants will undergo an
evaluation of symptoms and function and will undergo neurologic examination at the beginning
of the study, at 6 months and at 12 months. They will also be contacted at 3 and 9 months
by telephone. Studies will be done at 10 participating sites.
Official title: Double-Blind, Placebo-Controlled Study of Rifampicin in Multiple System Atrophy
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Primary outcome: Rate of Change from baseline to 12 months in the total UMSARS I score
Change from baseline to completion in total UMSARS score
Slope analysis: rate of progression in total UMSARS score from baseline to 12 months
Change from baseline to 12 months in UMSARS subscores
Whether or not a participant achieves a score of ≥3 on each of the following UMSARS questions: #1 (Speech impairment), #2 (Swallowing impairment), #8 (Falling)
Change from baseline to 12 months in the COMPASS_Select scale
Improvement in COMPASS_Select_change scale
MSA is a progressive, fatal disorder characterized by autonomic failure and parkinsonism
and/or cerebellar involvement. Neuropathologically, MSA is characterized by glial
cytoplasmic inclusions (GCI) of abnormally aggregated α-synuclein (α-syn). This is a study
to test the hypothesis that Rifampicin, because of its ability to inhibit the formation of
α-synuclein fibrils and disaggregate fibrils already formed, will delay progression or
reverse neurologic and autonomic functions and symptoms in MSA. This approach has been
proposed as a potential approach to treat parkinsonism and specifically, MSA. In an
experimental model of MSA, Rifampicin will improve behavioral abnormalities of MSA and halt
or reverse the pathological changes. The primary objective is to undertake a double-blind
placebo-controlled clinical trial on the effect of Rifampicin on progression of neurological
and autonomic failure in MSA.
Minimum age: 30 Years.
Maximum age: 80 Years.
- Participants aged 30-80 years old with a diagnosis of Possible or Probable MSA of the
parkinsonian subtype (MSA-P) or cerebellar subtype (MSA-C) according to The Gilman
- Participants who are less than 4 years from the time of documented MSA diagnosis.
- Participants with an anticipated survival of at least 3 years in the opinion of the
- Participants who are willing and able to give informed consent.
- "Normal" cognition as assessed by MMSE. We will require a value >24.
- Patients should be able to swallow capsules whole.
- Pregnant or lactating females.
- UMSARS score >17 on modified UMSARS I (question 11 eliminated).
- Participants with a clinically significant or unstable medical or surgical condition
that, in the opinion of the investigator, might preclude safe completion of the study
or might affect the results of the study. These include conditions causing
significant CNS or autonomic dysfunction, including congestive heart failure, recent
(<6 months) myocardial infarct, thrombocytopenia (<50 x10(9)/L), immunosuppressed
state, severe uncontrolled hypertension, severe cardiopulmonary disease, severe
anemia (<8g/dl), severe liver or kidney disease (creatinine >2. 3 mg/dl) uncontrolled
diabetes mellitus (HbA1c >10g%), alcoholism, malignant neoplasms, amyloidosis,
uncontrolled hypothyroidism, unstable peripheral neuropathies, concurrent infections,
orthopedic problems that compromise mobility and activity of daily living, severe
cerebrovascular accidents (such as hemiplegia, aphasia and non-dominant parietal lobe
syndrome), and neurotoxins or neuroactive drug exposure, parkinsonism due to drugs
(including neuroleptics, a-methyldopa, reserpine, metoclopramide).
- Participants who have taken any investigational products within 60 days prior to
- Women of child-bearing potential who do not practice an acceptable method of birth
control. Acceptable methods of birth control in this study are: surgical
sterilization, intrauterine devices, partner's vasectomy, a double-protection method
(condom or diaphragm with spermicide), hormonal contraceptive drug (i. e., oral
contraceptive, contraceptive patch, long-acting injectable contraceptive) with a
required second mode of contraception.
- Participants taking Tetrabenazine, Rasagiline or Selegiline. The participant will
qualify for the Rifampicin study after they have stopped these drugs for 3 months
- Participants known to have porphyria.
- Participants with abnormal liver function tests defined as 1. 5 times the upper limit
- Concomitant therapy with anticholinergic, alpha and beta adrenergic antagonists, or
other medications that affect autonomic function will be stopped prior to autonomic
evaluation according to Table 3 of Operations Manual.
- The regular use of neuroleptics within the six months prior to the initial
evaluation. Occasional use of a neuroleptic as an anti-emetic in the past is
allowed, providing not more than three doses were taken within the previous 12
- Since Rifampicin has significant drug-drug interactions, particular attention has
been devoted to the use of concomitant medications. Considering the target
population, we will exclude participants taking antifungal medication (itraconazole),
antiarrhythmics like amiodarone, digitalis and lorcainide, female hormones and
quetiapine (Seroquel). Use of methylphenidate, cinnarizine, reserpine, amphetamine,
atypical antipsychotics such as risperidone, olanzapine, and quetiapine or a MAO-A
inhibitor within one month prior to the baseline visit are also exclusionary. For
details, see Table 1 of Operations Manual.
- Diseases with features of PD; e. g., progressive supranuclear palsy, essential tremor,
inherited cerebellar degeneration, or postencephalitic parkinsonism.
- Dementia (DSM-IV criteria - Amer. Psych. Assoc., 1994). The score on the Mini-Mental
State Examination must be >24.
Locations and Contacts
UCLA Medical Center, Los Angeles, California 90095, United States; Not yet recruiting
Susan Perlman, MD, Phone: 310-794-1195, Email: SPerlman@mednet.ucla.edu
Susan Perlman, MD, Principal Investigator
University of California, San Diego, San Diego, California 92103, United States; Not yet recruiting
Stephanie Lessig, MD, Phone: 858-552-8585, Ext: 5409, Email: firstname.lastname@example.org
Stephanie Lessig, MD, Principal Investigator
Mayo Clinic, Jacksonville, Florida 32224, United States; Not yet recruiting
William Cheshire, MD, Phone: 904-953-7229, Email: email@example.com
William Cheshire, MD, Principal Investigator
University of South Florida, Tampa, Florida 33606, United States; Not yet recruiting
Robert A Hauser, MD, Phone: 813-844-4077, Email: firstname.lastname@example.org
Robert A Hauser, MD, Principal Investigator
Harvard Medical School, Boston, Massachusetts 02215, United States; Recruiting
Roy Freeman, MD, Phone: 617-632-8454, Email: email@example.com
Roy Freeman, MD, Principal Investigator
University of Michigan, Ann Arbor, Michigan 48109, United States; Not yet recruiting
Sid Gilman, MD, Phone: 734-936-1808, Email: firstname.lastname@example.org
Sid Gilman, MD, Principal Investigator
Mayo Clinic, Rochester, Minnesota 55905, United States; Recruiting
Tonette Gehrking, Phone: 507-284-0336, Email: email@example.com
Phillip A Low, MD, Principal Investigator
New York University, New York, New York 10016, United States; Recruiting
Horacio Kaufmann, MD, Phone: 212-263-7225, Email: firstname.lastname@example.org
Horacio Kaufmann, MD, Principal Investigator
Vanderbilt University, Nashville, Tennessee 37232, United States; Recruiting
David Robertson, MD, Phone: 615-343-6499, Email: email@example.com
David Robertson, MD, Principal Investigator
University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States; Recruiting
Steven Vernino, MD, Phone: 214-648-8816, Email: firstname.lastname@example.org
Steven Vernino, MD, Principal Investigator
Starting date: March 2011
Last updated: June 15, 2011