search
Back to results

Treating Multiple Sclerosis With Sirolimus, an Immune System Suppressor

Primary Purpose

Multiple Sclerosis (MS) - Relapsing-remitting

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
sirolimus
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Sclerosis (MS) - Relapsing-remitting focused on measuring relapsing-remitting MS, nonresponsive to standard of care MS, sirolimus

Eligibility Criteria

18 Years - 58 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

sirolimus

Arm Description

Outcomes

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)

Full Information

First Posted
November 2, 2004
Last Updated
September 20, 2016
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Autoimmunity Centers of Excellence
search

1. Study Identification

Unique Protocol Identification Number
NCT00095329
Brief Title
Treating Multiple Sclerosis With Sirolimus, an Immune System Suppressor
Official Title
A Phase I/II, Open-Label Pilot Trial to Evaluate the Safety of Rapamune (Sirolimus) in Patients With Multiple Sclerosis
Study Type
Interventional

2. Study Status

Record Verification Date
September 2016
Overall Recruitment Status
Terminated
Why Stopped
Due to slow recruitment.
Study Start Date
May 2003 (undefined)
Primary Completion Date
March 2005 (Actual)
Study Completion Date
March 2005 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Autoimmunity Centers of Excellence

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis (MS) - Relapsing-remitting
Keywords
relapsing-remitting MS, nonresponsive to standard of care MS, sirolimus

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
sirolimus
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
sirolimus
Primary Outcome Measure Information:
Title
Safety of sirolimus, including number of lesions detected by brain MRI
Title
Tolerability of sirolimus
Title
Mean number of new and overall total number of gadolinium-enhancing lesions reported on sequential brain MRIs
Secondary Outcome Measure Information:
Title
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
Title
Effect of sirolimus therapy on the immune function of patients with relapsing-remitting multiple sclerosis (RRMS)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
58 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Samia J. Khoury, MD
Organizational Affiliation
Center for Neurological Diseases, Brigham and Women's Hospital, Harvard Medical School
Official's Role
Principal Investigator
Facility Information:
Facility Name
Center for Neurological Diseases, Brigham and Women's Hospital, Harvard Medical School
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
15228759
Citation
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.
Results Reference
background
PubMed Identifier
15261567
Citation
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.
Results Reference
background
PubMed Identifier
15218806
Citation
Lucchinetti C, Bruck W. The pathology of primary progressive multiple sclerosis. Mult Scler. 2004 Jun;10 Suppl 1:S23-30. doi: 10.1191/1352458504ms1027oa.
Results Reference
background
PubMed Identifier
14610911
Citation
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.
Results Reference
background
Links:
URL
https://www.niaid.nih.gov/
Description
National Institute of Allergy and Infectious Diseases (NIAID)

Learn more about this trial

Treating Multiple Sclerosis With Sirolimus, an Immune System Suppressor

We'll reach out to this number within 24 hrs