- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00095329
Treating Multiple Sclerosis With Sirolimus, an Immune System Suppressor
A Phase I/II, Open-Label Pilot Trial to Evaluate the Safety of Rapamune (Sirolimus) in Patients With Multiple Sclerosis
Study Overview
Status
Intervention / Treatment
Detailed Description
MS is a chronic autoimmune disease of the central nervous system in which myelin, the protein sheath that protects nerve cells, is degraded by T cells and macrophages, leading to an eventual loss of neurologic function. MS can be classified as either relapsing-remitting, in which patients experience worsening in symptoms followed by partial or complete recovery of function; or progressive, in which patients have a gradual increase in symptoms, with or without relapses. Standard treatments used to treat relapsing-remitting MS are only modestly effective and may be associated with significant toxicity. There is a need to develop therapies with lower toxicities that can be administered early during the course of disease and have the potential to stop disease progression altogether. Sirolimus has been demonstrated to provide potent immunosuppression in recent clinical trials involving kidney transplantation, and may help people with autoimmune diseases like MS. This study will determine the benefit of sirolimus in MS patients.
Blood and urine collection will occur at screening. Participants will take daily doses of sirolimus for 6 months. There will be nine study visits; they will occur at Days 14, 28, 42, 56, 90, 120, 150, 180, and 225. Medication adverse events, concomitant medications, and vital signs will be recorded at Visits 1 through 8. At all visits, patient compliance to the sirolimus regimen will be measured, and blood and urine collection will occur. Physical and neurological exams, magnetic resonance imaging (MRI) brain scans, MS status tests, and a chest x-ray will be conducted at selected times throughout the study.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02115
- Center for Neurological Diseases, Brigham and Women's Hospital, Harvard Medical School
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Relapsing-remitting MS
- Evidence of demyelination on magnetic resonance imaging (MRI) scan
- Expanded Disability Status Scale (EDSS) score between 0 and 6
- Nonresponsive to beta-interferon or Glatiramer acetate therapy
- Discontinuation of beta-interferon or Glatiramer acetate therapy within 1 month prior to study entry
- Willing to use acceptable methods of contraception
Exclusion Criteria:
- Primary progressive MS
- Prior treatment with immunosuppressants
- Steroid therapy within 1 month prior to study entry
- Evidence of active infection or cancer
- Heart or hematologic dysfunction
- High levels of lipids in the blood
- Use of lipid-lowering agents
- History of cirrhosis or liver disease requiring treatment
- History of hepatitis B or C
- Active cytomegalovirus infection
- Kidney disease requiring treatment
- Active lung disease
- Diabetes
- Hyperthyroidism
- HIV infection
- Tuberculosis
- History of alcohol or drug abuse within 6 months prior to study entry
- Claustrophobia or inability to undergo MRI
- Pregnancy or breast-feeding
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: sirolimus
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
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Safety of sirolimus, including number of lesions detected by brain MRI
|
Tolerability of sirolimus
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Mean number of new and overall total number of gadolinium-enhancing lesions reported on sequential brain MRIs
|
Secondary Outcome Measures
Outcome Measure |
---|
Efficacy, as measured by change in the mean number of new and overall total number of gadolinium-enhancing lesions on pre-treatment brain MRIs, compared to post-treatment
|
Effect of sirolimus therapy on the immune function of patients with relapsing-remitting multiple sclerosis (RRMS)
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Samia J. Khoury, MD, Center for Neurological Diseases, Brigham and Women's Hospital, Harvard Medical School
Publications and helpful links
General Publications
- Meier DS, Weiner HL, Khoury SJ, Guttmann CR. Magnetic resonance imaging surrogates of multiple sclerosis pathology and their relationship to central nervous system atrophy. J Neuroimaging. 2004 Jul;14(3 Suppl):46S-53S. doi: 10.1177/1051228404266268.
- Gonsette RE. New immunosuppressants with potential implication in multiple sclerosis. J Neurol Sci. 2004 Aug 15;223(1):87-93. doi: 10.1016/j.jns.2004.04.025.
- Lucchinetti C, Bruck W. The pathology of primary progressive multiple sclerosis. Mult Scler. 2004 Jun;10 Suppl 1:S23-30. doi: 10.1191/1352458504ms1027oa.
- Kovarik JM, Burtin P. Immunosuppressants in advanced clinical development for organ transplantation and selected autoimmune diseases. Expert Opin Emerg Drugs. 2003 May;8(1):47-62. doi: 10.1517/14728214.8.1.47.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Nervous System Diseases
- Immune System Diseases
- Demyelinating Autoimmune Diseases, CNS
- Autoimmune Diseases of the Nervous System
- Demyelinating Diseases
- Autoimmune Diseases
- Multiple Sclerosis
- Sclerosis
- Physiological Effects of Drugs
- Anti-Infective Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Anti-Bacterial Agents
- Antibiotics, Antineoplastic
- Antifungal Agents
- Sirolimus
Other Study ID Numbers
- DAIT AMS02
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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