Treatment of Multiple Sclerosis Using Over the Counter Inosine

NCT ID: NCT00067327

Last Updated: 2006-03-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-02-28
• Study Completion Date: 2005-09-30

Brief Summary

The purpose of this study is to determine whether raising low levels of the natural antioxidant uric acid by the administration of a precursor, inosine, has any therapeutic effect on the progression of Relapsing Remitting Multiple Sclerosis (RRMS) and secondary progressive Multiple Sclerosis (MS).

Detailed Description

Uric acid is a natural inhibitor of certain chemistries associated with peroxynitrite, a product of inflammation. In animal models of multiple sclerosis (MS), these chemical reactions have been associated with breakdown of the blood-brain barrier and CNS tissue damage. In addition, MS patients have serum uric acid levels that are lower than age- and sex- matched healthy individuals. The primary purpose of this study to determine whether raising low serum uric acid levels by daily oral administration of its precursor inosine has an effect on the cumulative number of newly active lesions on magnetic resonance imaging (MRI) and to evaluate the safety and tolerability of inosine in patients diagnosed with relapsing remitting and secondary progressive MS.

Conditions

Multiple Sclerosis, Relapsing-Remitting

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Interventions

Inosine

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Nonpregnant, nonlactating females
• Females of child bearing potential must have a negative human chorionic gonadotropin (HCG) test result within 60 days before the first dose of study material.
• Males and females must practice adequate contraception, in the judgement of the investigator, during the course of the study.
• Subjects must have a diagnosis of clinically definite Relapsing Remitting Multiple Sclerosis based on medical history, physical examination, laboratory test results, and neurologic examination. Alternatively, subjects may have clinically probable MS characterized by 1 attack and the presence of at least 4 lesions on MRI within 12 months before the initial baseline evaluation.
• Subjects must have an Expanded Disability Status Scale (EDSS) test result of less than or equal to 5.0 within 60 days before the first dose of study material.
• Subjects will have serum uric acid levels less than 5 mg/dl.
• Have 1 clinical relapse in the last year

Exclusion Criteria

• Presence of any medical disability or laboratory test result that, in the judgement of the investigator, would interfere with assessment of the tolerability, safety, or efficacy of study material or would compromise the subject's ability to provide informed consent.
• Evidence of active infection characterized by requiring treatment with antibiotics within 7 days before the first dose of study material.
• Treatment with interferons, glatiramer acetate, lymphoid irradiation, cyclophosphamide, or with other immune modifying treatments within 3 months, or corticosteroids within 1 month before the initial baseline MRI assessment in this trial.
• Recent history (within the previous 2 years) of drug or alcohol abuse.
• Known allergy to Inosine products or history of anaphylaxis.
• Previous randomization into this study.
• Treatment with an investigational agent within 30 days before the first dose of study material.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Center for Complementary and Integrative Health (NCCIH)

NIH

Sponsor Role: lead

Principal Investigators

Douglas C Hooper, PhD

Role: PRINCIPAL_INVESTIGATOR

Thomas Jefferson University

Hilary Koprowski, MD

Role: STUDY_DIRECTOR

Department of Microbiology and Immunology, Thomas Jefferson University

Locations

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

References

Hooper DC, Spitsin S, Kean RB, Champion JM, Dickson GM, Chaudhry I, Koprowski H. Uric acid, a natural scavenger of peroxynitrite, in experimental allergic encephalomyelitis and multiple sclerosis. Proc Natl Acad Sci U S A. 1998 Jan 20;95(2):675-80. doi: 10.1073/pnas.95.2.675.

Reference Type: BACKGROUND

PMID: 9435251 (View on PubMed)

Hooper DC, Scott GS, Zborek A, Mikheeva T, Kean RB, Koprowski H, Spitsin SV. Uric acid, a peroxynitrite scavenger, inhibits CNS inflammation, blood-CNS barrier permeability changes, and tissue damage in a mouse model of multiple sclerosis. FASEB J. 2000 Apr;14(5):691-8. doi: 10.1096/fasebj.14.5.691.

Reference Type: BACKGROUND

PMID: 10744626 (View on PubMed)

Koprowski H, Spitsin SV, Hooper DC. Prospects for the treatment of multiple sclerosis by raising serum levels of uric acid, a scavenger of peroxynitrite. Ann Neurol. 2001 Jan;49(1):139. doi: 10.1002/1531-8249(200101)49:13.0.co;2-a. No abstract available.

Reference Type: BACKGROUND

PMID: 11198290 (View on PubMed)

Spitsin S, Hooper DC, Leist T, Streletz LJ, Mikheeva T, Koprowskil H. Inactivation of peroxynitrite in multiple sclerosis patients after oral administration of inosine may suggest possible approaches to therapy of the disease. Mult Scler. 2001 Oct;7(5):313-9. doi: 10.1177/135245850100700507.

Reference Type: BACKGROUND

PMID: 11724447 (View on PubMed)

Other Identifiers

R21AT001301-01A1

Identifier Type: NIH

Identifier Source: org_study_id

View Link