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

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)

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.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Interferon beta 1a, oral doxycycline

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Louisiana
    • Shreveport, Louisiana, United States, 71103
      • LSU Health Sciences Center Shreveport

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Single Arm; Interferon beta 1a, oral doxycycline	Drug: Interferon beta 1a, oral doxycycline; Patients took intramuscular interferon beta 1a, 30 micrograms, for 3 months then added oral doxycycline, 100 daily with the interferon for 4 months.; Other Names: Avonex

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Louisiana State University Health Sciences Center Shreveport
• Collaborators: Biogen
• Investigators: Principal Investigator: Alireza Minagar, MD, LSU Health Sciences Center -Shreveport

Publications and helpful links

General Publications

• Minagar A, Alexander JS, Schwendimann RN, Kelley RE, Gonzalez-Toledo E, Jimenez JJ, Mauro L, Jy W, Smith SJ. Combination therapy with interferon beta-1a and doxycycline in multiple sclerosis: an open-label trial. Arch Neurol. 2008 Feb;65(2):199-204. doi: 10.1001/archneurol.2007.41. Epub 2007 Dec 10.

Study record dates

Study Major Dates

• Study Start: December 1, 2003
• Primary Completion (ACTUAL): August 1, 2009
• Study Completion (ACTUAL): October 1, 2009

Study Registration Dates

• First Submitted: October 27, 2005
• First Submitted That Met QC Criteria: October 27, 2005
• First Posted (ESTIMATE): October 30, 2005

Study Record Updates

• Last Update Posted (ACTUAL): November 8, 2022
• Last Update Submitted That Met QC Criteria: October 11, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Immunologic Factors; Anti-Bacterial Agents; Adjuvants, Immunologic; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Interferons; Interferon beta-1a; Doxycycline; Interferon-beta
• Other Study ID Numbers: H04-090