Multiple Sclerosis
Conditions
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.
Interventions
DRUGInterferon 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.
Sponsors
Biogen
Louisiana State University Health Sciences Center Shreveport
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Inteferon, Then Interferon With Doxycycline 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. | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Inteferon, Then Interferon With Doxycycline |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants |
| Age, Continuous | 44.5 years STANDARD_DEVIATION 10.6 |
| Region of Enrollment United States | 16 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 16 |
| serious Total, serious adverse events | 0 / 16 |
Outcome results
Primary
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.
Time frame: 8 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Inteferon, Then Interferon With Doxycycline | Gadolinium-enhancing (Gd+)Lesion Number Change. | 4.0 Gd+ lesions |
Secondary
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.
Time frame: 8 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Inteferon, Then Interferon With Doxycycline | Relapse Rates, Serum Matrix Metalloproteinase 9 Levels, Transendothelial Migration of Monocytes | 15 participants |