Treating Multiple Sclerosis With Sirolimus, an Immune System Suppressor

September 20, 2016 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

A Phase I/II, Open-Label Pilot Trial to Evaluate the Safety of Rapamune (Sirolimus) in Patients With Multiple Sclerosis

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.

Study Overview

Status

Terminated

Conditions

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

Interventional

Enrollment (Actual)

14

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Center for Neurological Diseases, Brigham and Women's Hospital, Harvard Medical School

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 58 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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
Biological: sirolimus

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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

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

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Autoimmunity Centers of Excellence

Investigators

  • Principal Investigator: Samia J. Khoury, MD, Center for Neurological Diseases, Brigham and Women's Hospital, Harvard Medical School

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2003

Primary Completion (Actual)

March 1, 2005

Study Completion (Actual)

March 1, 2005

Study Registration Dates

First Submitted

November 2, 2004

First Submitted That Met QC Criteria

November 2, 2004

First Posted (Estimate)

November 3, 2004

Study Record Updates

Last Update Posted (Estimate)

September 22, 2016

Last Update Submitted That Met QC Criteria

September 20, 2016

Last Verified

September 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

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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