Safety and Efficacy Study of Doxycycline in Combination With Interferon-B-1a to Treat Multiple Sclerosis

Study Overview
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Brief Summary
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To evaluate the efficacy, safety, and tolerability of combination therapy with intramuscular interferon beta-1a and oral doxycycline, a potent inhibitor of matrix metalloproteinases, in patients with relapsing remitting multiple sclerosis (RRMS) having breakthrough disease activity.

Detailed Description
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Eligible individuals were evaluated monthly for 3 months while taking intramuscular interferon beta-1a, 30 micrograms weekly, then monthly for 4 months while receiving intramuscular interferon beta-1a, 30 micrograms and oral doxycycline, 100 mg daily.

Official Title
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An Open Label Trial of Safety and Efficacy of Combination Therapy With Interferon-B-1a and Oral Doxycycline in Patients With Relapsing-remitting Multiple Sclerosis (RRMS)

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Interferon beta 1a, oral doxycycline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 18-55 Relapsing-Remitting Multiple Sclerosis (RRMS) Avonex therapy for 6 months prior continuous annualized relapse rate >2 during Avonex therapy most recent relapse within 60 days of baseline entry Expanded Disability Status Scale (EDSS) 1.5-4.5 one or more gadolinium (Gd+) MRI lesions on a baseline MRI no history of immune modulator or immunosuppressant therapy used in combination with Avonex (other then GSC administer for clinical relapses) not participating in any other study of ms therapeutics Serum neutralizing antibodies (NABs) titer to Avonex <20 Exclusion Criteria: Medical or Psychiatric conditions that will affect patients ability to provide informed consent inability to undergo MRI clinically serious medical conditions or significantly abnormal labs no use of these medications or procedures within six months prior to study: *monoclonal antibodies,total lymphoid radiation,systemic steroids,cytotoxic or immunosuppressive medications such as mitoxantrone or cyclophosphamide or any other investigational drugs Interferon neutralizing antibody titers >20 no breast feeding or pregnant no patients with any systemic illness,psychiatric condition or other disorder that would concern safety of patient to complete procedures of protocol abnormal blood test clinically significant abnormality on chest x-ray (CXR)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Arm<br>Interferon beta 1a, oral doxycycline | Drug: Interferon beta 1a, oral doxycycline<br>* Patients took intramuscular interferon beta 1a, 30 micrograms, for 3 months then added oral doxycycline, 100 daily with the interferon for 4 months.<br>* Other names: Avonex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gadolinium-enhancing (Gd+)Lesion Number Change. | Before treatment is the number of lesions per image from months -3, -2, -1, and 0. During treatment is the number of lesions from months 1,2, and 3. The mean number of Gd+ lesions during each treatment period was calculated for each patient as the total number of Gd+ lesions observed across all images divided by the number of images. Hence, the mean number of Gd+ lesions per patient represents the number of lesions per MRI. | 8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse Rates, Serum Matrix Metalloproteinase 9 Levels, Transendothelial Migration of Monocytes | Only 1 patient relapsed. Correlations between decrease serum metalloproteinase 9 levels and enhancing lesion activity reduction. Transendothelial migration of monocytes was suppressed. Adverse effects were mild. No adverse synergistic effects of combination therapy. | 8 months |