Treating Multiple Sclerosis With Sirolimus, an Immune System Suppressor

This study has been terminated.
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID) Identifier:
First received: November 2, 2004
Last updated: January 16, 2013
Last verified: January 2013
The purpose of this study is to determine the safety and tolerability of the drug sirolimus in patients with multiple sclerosis (MS) who have failed other treatments.

Condition Intervention Phase
Multiple Sclerosis
Biological: Sirolimus
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II, Open-Label Pilot Trial to Evaluate the Safety of Rapamune (Sirolimus) in Patients With Multiple Sclerosis

Resource links provided by NLM:

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Safety of sirolimus, including number of lesions detected by brain MRI
  • tolerability of sirolimus
  • mean number of new and overall total number of gadolinium-enhancing lesions reported on sequential brain MRIs

Secondary Outcome Measures:
  • 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)

Enrollment: 8
Study Start Date: May 2003
Study Completion Date: January 2007
Arms Assigned Interventions
Experimental: PATIENTS WITH MULTIPLE SCLEROSIS Biological: Sirolimus

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.


Ages Eligible for Study:   18 Years to 58 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
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Please refer to this study by its identifier: NCT00095329

United States, Massachusetts
Center for Neurological Diseases, Brigham and Women's Hospital, Harvard Medical School
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Principal Investigator: Samia J. Khoury, MD Center for Neurological Diseases, Brigham and Women's Hospital, Harvard Medical School
  More Information

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID) Identifier: NCT00095329     History of Changes
Other Study ID Numbers: DAIT AMS02 
Study First Received: November 2, 2004
Last Updated: January 16, 2013
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Treatment Failure

Additional relevant MeSH terms:
Multiple Sclerosis
Autoimmune Diseases
Autoimmune Diseases of the Nervous System
Demyelinating Autoimmune Diseases, CNS
Demyelinating Diseases
Immune System Diseases
Nervous System Diseases
Pathologic Processes
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Physiological Effects of Drugs processed this record on May 26, 2016