Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Futility Trial of Sirolimus in Multiple System Atrophy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03589976
Recruitment Status : Recruiting
First Posted : July 18, 2018
Last Update Posted : October 5, 2018
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
NYU Langone Health

Brief Summary:
Single-center, randomized, placebo-controlled, phase-II, futility clinical trial to determine if oral sirolimus is of sufficient promise to slow disease progression in MSA, prior to embarking on a large-scale and costly phase III study to assess its efficacy. A futility design under the null hypothesis assumes that sirolimus will slow the progression of the disease, whereas the alternative hypothesis assumes no benefit of sirolimus. If the null hypothesis is rejected (i.e., futility of sirolimus to slow progression of MSA), a major phase III study will be discouraged, whereas non-futility will offer strong support for a phase III trial to detect clinical efficacy.

Condition or disease Intervention/treatment Phase
Multiple System Atrophy Drug: Sirolimus 2 MG Other: Placebo Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 56 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Single Center Randomized,Double Blind, Placebo-controlled Futility Trial to Determine if Sirolimus is of Sufficient Promise to Slow the Progression of Multiple System Atrophy
Actual Study Start Date : September 1, 2018
Estimated Primary Completion Date : August 2021
Estimated Study Completion Date : August 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Sirolimus

Arm Intervention/treatment
Experimental: Sirolimus
2 mg/day (one 2-mg tablet/day). The dose of sirolimus will be adjusted throughout the trial based on sirolimus plasma levels and the presence of drug-related adverse events. The maximum dose of sirolimus will be6 mg/day (three 2-mg tablets/day).
Drug: Sirolimus 2 MG
Dose will be adjusted trhoughout this trial based on sirolimus plasma levels and the presence of drug-related adverse events.The maximum dose will be 6mg/day.

Placebo Comparator: Placebo
Patients receiving placebo will undergo analog sham level measurements and the number of tablets will be also adjusted to maintain the blinding of the trial.
Other: Placebo
Patients receiving placebo will undergo analog sham level measurements and the number of tablets will be also adjusted to maintain the blinding of the trial.




Primary Outcome Measures :
  1. Change from baseline to 48 weeks in United Multiple System Atrophy Rating Score (UMSARS) total score in patients taking sirolimus [ Time Frame: 48 Weeks ]

    UMSARS is a validated, disease-specific scale representing the diverse signs and symptoms in MSA. Higher scores on the UMSARS scales mean poorer health.

    USMARS has an Activities of Daily Living score (UMSARS-1, 12 questions) that evaluates motor including autonomic activities and the Motor Examination score (UMSARS-2, 14 questions). UMSARS-3 measures supine/standing BP and UMSARS-4 is a disability scale.


  2. Change from baseline to 48 weeks in United Multiple System Atrophy Rating Score (UMSARS) total score in historical controls [ Time Frame: 48 Weeks ]

    UMSARS is a validated, disease-specific scale representing the diverse signs and symptoms in MSA. Higher scores on the UMSARS scales mean poorer health.

    USMARS has an Activities of Daily Living score (UMSARS-1, 12 questions) that evaluates motor including autonomic activities and the Motor Examination score (UMSARS-2, 14 questions). UMSARS-3 measures supine/standing BP and UMSARS-4 is a disability scale.



Secondary Outcome Measures :
  1. Change from baseline to 48 weeks in United Multiple System Atrophy Rating Score (UMSARS) subscores (UMSARS-1 and UMSARS-2) in patients taking sirolimus [ Time Frame: 48 Weeks ]
    UMSARS-2 score (neurological examination) progression at week 48 compared to baseline; the UMSARS-1 score (activity of daily living) progression at week 48 compared to baseline.

  2. Change from baseline to 48 weeks in United Multiple System Atrophy Rating Score (UMSARS) subscores (UMSARS-1 and UMSARS-2) in historical controls [ Time Frame: 48 Weeks ]
    UMSARS-2 score (neurological examination) progression at week 48 compared to baseline; the UMSARS-1 score (activity of daily living) progression at week 48 compared to baseline.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   30 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants aged 30-80 years old with a diagnosis of MSA based on clinical criteria and standardized autonomic testing. This approach allows for identification of patients with MSA with very high specificity and is yet sensitive enough to allow for enrollment of patients at a disease stage at which an intervention on the natural disease course has a meaningful impact on patient outcome. Patients therefore have to fulfill current consensus criteria (1) for probable MSA of the parkinsonian subtype (MSA-P) or cerebellar subtype (MSA-C) and have findings on autonomic function testing suggestive of MSA.
  • Participants who are less than 4 years from the time of documented MSA diagnosis.
  • Participants who are still able to walk with or without assistance.
  • Participants with an anticipated survival of at least 3 years in the opinion of the investigator.
  • Participants who are willing and able to give informed consent.
  • Montreal Cognitive Asessment (MoCA) > 20.
  • Ability to take oral medication and be willing to adhere to the study drug regimen
  • For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 8 weeks after the end of study drug administration
  • For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner
  • Agreement to adhere to Lifestyle Considerations (see section 5.3) throughout study duration

Exclusion Criteria:

  • Women of childbearing 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 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 central nervous system (CNS) or autonomic dysfunction, including congestive heart failure, recent (<6 months) myocardial infarct, cardiopulmonary disease, severe, uncontrolled hypertension, thrombocytopenia (< 50 x 10(9)/L), severe anemia (< 8g/dl), immunocompromised state, liver or kidney disease (creatinine > 1.5 mg/dl or proteinuria > 20 mg/dl), uncontrolled diabetes mellitus (HbA1c >10g%), alcoholism, amyloidosis, uncontrolled hypothyroidism, sympathectomy, unstable peripheral neuropathies, concurrent infections, orthopedic problems that compromise mobility and activity of daily living, cerebrovascular accidents, neurotoxin or neuroactive drug exposure, parkinsonism due to drugs (including neuroleptics, alpha-methyldopa, reserpine, metoclopramide).
  • Participants with high LDL cholesterol levels (LDL > 160 mg/dL) and/or high triglycerides levels (> 200 mg/dL).
  • Participants with latent tuberculosis infection as defined as positive interferon-gamma release-assay (QUANTIferon®).
  • Participants with history of tuberculosis
  • Participants with a history of active, acute or chronic, or latent hepatitis B or hepatitis C.
  • Participants with human immunodeficiency virus (HIV) infection, or other congenital or acquired causes of immunosuppression.
  • Participants with active malignant neoplasms or history of malignant neoplasm in the last 5 years.
  • Movement disorders other than MSA; e.g., Parkinson disease, dementia with Lewy bodies, essential tremor, progressive supranuclear palsy, spinocerebellar ataxia, spastic paraparesis, corticobasal degeneration, or vascular, pharmacological or post-encephalitic parkinsonism.
  • Dementia (DSM-V criteria).
  • History of electroconvulsive therapy.
  • History of deep brain stimulation surgery.
  • Patients with contraindication for MRI scanning, including those with MRI-incompatible pacemaker
  • History of organ transplant
  • Participants who have taken any investigational products within 60 days prior to baseline.
  • Treatment with cyclosporine, corticosteroids, methotrexate, rituximab within 3 months prior to baseline.
  • Treatment with inhibitors of CYP3A4 (which may decrease the metabolism of sirolimus and increase sirolimus levels): nicardipine, verapamil, clotrimazole, fluconazole, itraconazole, clarithromycin, erythromycin, troleandomycin, cisapride, metoclopramide, bromocriptine, cimetidine, danazol, HIV-protease inhibitors (e.g., ritonavir, indinavir); grapefruit.
  • Treatment with inducers of CYP3A4 (which may increase the metabolism of sirolimus and decrease sirolimus levels): carbamazepine, phenobarbital, phenytoin, rifabutin, rifapentine.
  • Inability or unwillingness of subject or legal guardian/representative to give written informed consent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03589976


Contacts
Layout table for location contacts
Contact: Jose Martinez, MD 212-263-7225 Jose.Martinez4@nyulangone.org

Locations
Layout table for location information
United States, New York
New York University School of Medicine Recruiting
New York, New York, United States, 10016
Contact: Jose Martinez, MA    212-263-7225    Jose.Martinez4@nyulangone.org   
Principal Investigator: Jose A Palma Carazo, MD         
Sponsors and Collaborators
NYU Langone Health
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
Layout table for investigator information
Principal Investigator: Jose A Palma Carazo NYU Langone Health

Layout table for additonal information
Responsible Party: NYU Langone Health
ClinicalTrials.gov Identifier: NCT03589976     History of Changes
Other Study ID Numbers: 17-01392
First Posted: July 18, 2018    Key Record Dates
Last Update Posted: October 5, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
Supporting Materials: Study Protocol
Time Frame: Beginning 3 months and ending 5 years following article publication.
Access Criteria: Researchers who provide a methodologically sound proposal that has been approved by a local Institutional Review Board.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Atrophy
Multiple System Atrophy
Shy-Drager Syndrome
Pathological Conditions, Anatomical
Primary Dysautonomias
Autonomic Nervous System Diseases
Nervous System Diseases
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Hypotension
Vascular Diseases
Cardiovascular Diseases
Sirolimus
Everolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs