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

Sponsor:	Louisiana State University Health Sciences Center Shreveport
Collaborator:	Biogen Idec
Information provided by (Responsible Party):	Alireza Minagar, Louisiana State University Health Sciences Center Shreveport
ClinicalTrials.gov Identifier:	NCT00246324

Purpose

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.

Condition	Intervention	Phase
Multiple Sclerosis	Drug: Interferon beta 1a, oral doxycycline	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	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)

Resource links provided by NLM:

MedlinePlus related topics: Multiple Sclerosis

Drug Information available for: Doxycycline Doxycycline hyclate Interferon beta Interferon-beta Doxycycline calcium Interferon beta 1a Interferons

U.S. FDA Resources

Further study details as provided by Louisiana State University Health Sciences Center Shreveport:

Primary Outcome Measures:

Gadolinium-enhancing (Gd+)Lesion Number Change. [ Time Frame: 8 months ] [ Designated as safety issue: Yes ]
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:

Relapse Rates, Serum Matrix Metalloproteinase 9 Levels, Transendothelial Migration of Monocytes [ Time Frame: 8 months ] [ Designated as safety issue: Yes ]
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.
Determine Safety and Tolerability of Combination Therapy With Avonex Plus Doxycycline [ Time Frame: 8 months ] [ Designated as safety issue: Yes ]
Determine Pre- and On-treatment Cytokine ELISA, MMP ELISA and Bioassay [ Time Frame: 8 months ] [ Designated as safety issue: Yes ]

Enrollment:	16
Study Start Date:	December 2003
Study Completion Date:	October 2009
Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

Intervention Details:

Patients took intramuscular interferon beta 1a, 30 micrograms, for 3 months then added oral doxycycline, 100 daily with the interferon for 4 months.

Other Name: Avonex

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.

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00246324

Locations

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

Sponsors and Collaborators

Louisiana State University Health Sciences Center Shreveport

Biogen Idec

Investigators

Principal Investigator:

Alireza Minagar, MD

LSU Health Sciences Center -Shreveport

More Information

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. Epub 2007 Dec 10.

Responsible Party:	Alireza Minagar, Assistant Professor Department of Neurology, Louisiana State University Health Sciences Center Shreveport
ClinicalTrials.gov Identifier:	NCT00246324 History of Changes
Other Study ID Numbers:	H04-090
Study First Received:	October 27, 2005
Results First Received:	May 5, 2011
Last Updated:	October 7, 2011
Health Authority:	United States: Institutional Review Board

Additional relevant MeSH terms:

Multiple Sclerosis
Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Interferon-beta
Interferons
Interferon beta 1a
Doxycycline hyclate

Doxycycline
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Anti-Bacterial Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on February 13, 2012