Treating Multiple Sclerosis With Sirolimus, an Immune System Suppressor

NCT ID: NCT00095329

Last Updated: 2016-09-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-05-31
• Study Completion Date: 2005-03-31

Brief Summary

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.

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.

Conditions

Multiple Sclerosis (MS) - Relapsing-remitting

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

sirolimus

Group Type: EXPERIMENTAL

sirolimus

Intervention Type: BIOLOGICAL

Interventions

sirolimus

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 58 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Autoimmunity Centers of Excellence

OTHER

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Samia J. Khoury, MD

Role: PRINCIPAL_INVESTIGATOR

Center for Neurological Diseases, Brigham and Women's Hospital, Harvard Medical School

Locations

Center for Neurological Diseases, Brigham and Women's Hospital, Harvard Medical School

Boston, Massachusetts, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 15228759 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15261567 (View on PubMed)

Lucchinetti C, Bruck W. The pathology of primary progressive multiple sclerosis. Mult Scler. 2004 Jun;10 Suppl 1:S23-30. doi: 10.1191/1352458504ms1027oa.

Reference Type: BACKGROUND

PMID: 15218806 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 14610911 (View on PubMed)

Related Links

https://www.niaid.nih.gov/

National Institute of Allergy and Infectious Diseases (NIAID)

Other Identifiers

DAIT AMS02

Identifier Type: -

Identifier Source: org_study_id