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

• Sponsor: Louisiana State University Health Sciences Center Shreveport (Other)
• Overall Status: Completed
• CT.gov ID: NCT00246324
• Collaborator: Biogen (Industry)
• Enrollment: 16
• Location: 1
• Arm: 1
• Duration (Months): 70
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis	Drug: Interferon beta 1a, oral doxycycline	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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)
• Study Start Date: Dec 1, 2003
• Actual Primary Completion Date: Aug 1, 2009
• Actual Study Completion Date: Oct 1, 2009

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. Determine Safety and Tolerability of Combination Therapy With Avonex Plus Doxycycline [8 months]

3. Determine Pre- and On-treatment Cytokine ELISA, MMP ELISA and Bioassay [8 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Locations

	Site	City	State	Country	Postal Code
1	LSU Health Sciences Center Shreveport	Shreveport	Louisiana	United States	71103

Sponsors and Collaborators

• Louisiana State University Health Sciences Center Shreveport
• Biogen

Investigators

• Principal Investigator: Alireza Minagar, MD, LSU Health Sciences Center -Shreveport

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Louisiana State University Health Sciences Center Shreveport
• ClinicalTrials.gov Identifier: NCT00246324
• Other Study ID Numbers: H04-090
• First Posted: Oct 30, 2005
• Last Update Posted: Jul 22, 2020
• Last Verified: Jul 1, 2020

• Additional relevant MeSH terms: Multiple Sclerosis; Sclerosis; Interferons; Interferon-beta; Interferon beta-1a; Doxycycline

Study Results

Participant Flow

Arm/Group Title	Inteferon, Then Interferon With Doxycycline
Arm/Group Description	Men and women with RRMS who had received interferon beta-1a intramuscularly for at least six months and were experiencing breakthrough disease activity with the most recent relapse within 60 days of study entry.
Period Title: Overall Study
STARTED	16
COMPLETED	15
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Inteferon, Then Interferon With Doxycycline
Arm/Group Description	Men and women with RRMS who had received interferon beta-1a intramuscularly for at least six months and were experiencing breakthrough disease activity with the most recent relapse within 60 days of study entry.
Overall Participants	16
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	16 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.5 (10.6)
Sex: Female, Male (Count of Participants)
Female	12 75%
Male	4 25%
Region of Enrollment (participants) [Number]
United States	16 100%

Outcome Measures

1. Primary Outcome

Title	Gadolinium-enhancing (Gd+)Lesion Number Change.
Description	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.
Time Frame	8 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Inteferon, Then Interferon With Doxycycline
Arm/Group Description	Men and women with RRMS who had received interferon beta-1a intramuscularly for at least six months and were experiencing breakthrough disease activity with the most recent relapse within 60 days of study entry.
Measure Participants	16
Median (95% Confidence Interval) [Gd+ lesions]	4.0

2. Secondary Outcome

Title	Relapse Rates, Serum Matrix Metalloproteinase 9 Levels, Transendothelial Migration of Monocytes
Description	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.
Time Frame	8 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Inteferon, Then Interferon With Doxycycline
Arm/Group Description	Men and women with RRMS who had received interferon beta-1a intramuscularly for at least six months and were experiencing breakthrough disease activity with the most recent relapse within 60 days of study entry.
Measure Participants	16
Number [participants]	15 93.8%

3. Secondary Outcome

Title	Determine Safety and Tolerability of Combination Therapy With Avonex Plus Doxycycline
Time Frame	8 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Determine Pre- and On-treatment Cytokine ELISA, MMP ELISA and Bioassay
Time Frame	8 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Adverse event data was collected for 7 months
Arm/Group Title	Inteferon, Then Interferon With Doxycycline
Arm/Group Description	Men and women with RRMS who had received interferon beta-1a intramuscularly for at least six months and were experiencing breakthrough disease activity with the most recent relapse within 60 days of study entry.
All Cause Mortality
	Inteferon, Then Interferon With Doxycycline
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Inteferon, Then Interferon With Doxycycline
	Affected / at Risk (%)	# Events
Total	0/16 (0%)
Other (Not Including Serious) Adverse Events
	Inteferon, Then Interferon With Doxycycline
	Affected / at Risk (%)	# Events
Total	0/16 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.