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

Phase 4

Completed

Brief Summary: 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: 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.

Recruitment & Eligibility

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)

Arm && Interventions

Group	Intervention	Description
Single Arm	Interferon beta 1a, oral doxycycline	Interferon beta 1a, oral doxycycline

Primary Outcome Measures

Name	Time	Method
Gadolinium-enhancing (Gd+)Lesion Number Change.	8 months	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.

Secondary Outcome Measures

Name	Time	Method
Relapse Rates, Serum Matrix Metalloproteinase 9 Levels, Transendothelial Migration of Monocytes	8 months	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.