Autonomic Disorders Consortium

Research Studies

6102: An Oligo-centered, Randomized, Double-blind, Placebo-controlled Clinical Trial to Assess the Efficacy, Safety, and Tolerability of Rifampicin in Patients with Multiple System Atrophy

Status: No Longer Recruiting

Study Summary

Please Note: The Rare Diseases Clinical Research Network will make every effort to enroll all the patients we can, but we cannot make any guarantees that we will be able to enroll everyone in a particular study who wants to participate.

For Diseases: Multiple System Atrophy (MSA)


MSA is a progressive, fatal disorder characterized by autonomic failure and parkinsonism and/or cerebellar involvement. The key pathologic change in the brain consists of glial cytoplasmic inclusions (GCI). GCI consists of abnormally aggregated α-synuclein (α-syn) fibrils.

This is a study to evaluate if 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 an approach to treat parkinsonism and specifically, MSA. In an experimental model of MSA, Rifampicin will improve the motor 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.

About this Study

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.

Targeted Enrollment

To be eligible to participate, you must:

  • Be 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 Criteria (2008).
  • Have less than 4 years from the time of documented MSA diagnosis.
  • Have an anticipated survival of at least 3 years in the opinion of the investigator.
  • Be willing and able to give informed consent.
  • Have “normal” cognition as assessed by MMSE. We will require a value > 24.
  • Be able to swallow capsules whole.

You are not eligible to participate if you:

  • Are pregnant or lactating.
  • Have a UMSARS score >17 on modified UMSARS I (question 11 eliminated).
  • Have 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).
  • Have taken any investigational products within 60 days prior to baseline.
  • Are a women of child-bearing potential who does 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.
  • Are taking Tetrabenazine, Rasagiline or Selegiline. The participant will qualify for the Rifampicin study after they have stopped these drugs for 3 months
  • Are known to have porphyria.
  • You have abnormal liver function tests defined as 1.5 times the upper limit of normal.
  • Have 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.
  • Have had 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 months.
  • 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, 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.
  • Have a disease with features of PD (e.g., progressive supranuclear palsy, essential tremor, inherited cerebellar degeneration, or postencephalitic parkinsonism.)
  • Have dementia (DSM-IV criteria - Amer. Psych. Assoc., 1994). The score on the Mini-Mental State Examination must be >24.

Join the Contact Registry for Multiple system atrophy (MSA)