Pulse ACTH vs. MP for MS

Study Overview
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Brief Summary
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We hypothesize that corticotropin or adrenocorticotrophic hormone (ACTH), administered as Acthar Gel® (MANUFACTURER NAME) is effective in the control of clinical disease activity as a pulse therapy for relapsing-remitting MS when added to standard treatment with beta-interferon. We wish to determine whether ACTH, when administered as clustered monthly intramuscular injections (monthly pulse therapy) as add-on to beta-interferons, may be a safe and effective alternative to monthly pulse therapy with MP. In addition, we hypothesize that pulse therapy with ACTH alters immune function to favor a regulatory, rather than a pro-inflammatory T cell environment.

Detailed Description
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Please see the final manuscript

Official Title
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Comparison of Monthly Pulse ACTH (Acthar Gel) Therapy With Methylprednisolone (MP, Solumedrol) for Long-Term Treatment of Multiple Sclerosis (MS) as an Add on Therapy to Beta-interferons (Avonex, Betaseron or Rebif)

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: ACTH
* Drug: Methylprednisolone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinically definite multiple sclerosis defined by McDonald Criteria. Between 18-65 years of age. Subject must able to understand and sign the IRB- approved informed consent form prior to the performance of any study-specific procedures and is willing to comply with the required scheduling and assessments of the protocol, including self-administration of study drug (if assigned to the ACTH arm). Subjects who are women of childbearing potential, must have a negative serum pregnancy test at the screening visit, and must be willing to practice a reliable birth-control method. Subjects must have at least one MS relapse within last year and/or at least one new T2 or Gadolinium-enhanced lesion on MRI while on stable interferon therapy. EDSS (Expanded Disability Status Scale) score of 3.0 - 6.5 Currently on one of the approved beta-interferon drugs (Avonex, Betaseron, or Rebif) for a minimum of 6 months. Exclusion Criteria: Women who are either pregnant or breastfeeding, and women of child-bearing potential (defined as not surgically sterile or at least two years post menopausal) who are not using one of the following birth control methods: tubal ligation, implantable contraception device, oral, patch, injectable or transdermal contraceptive, barrier method or sexual activity restricted to vasectomized partner. Uncontrolled hypertension, clinically significant cardiac arrhythmias, gastrointestinal ulcer, uncontrolled diabetes mellitus, osteoporosis, any stage of renal failure, psychiatric disorders or any other clinically significant general health conditions that may interfere with the trial participation. Subject has a history of drug or alcohol abuse within the past year. Subject had corticosteroid treatment within last 90 days. Subject started new medication within last 30 days. Subject is on Tysabri treatment presently or within 6 months of screening. Subject is on Novantrone, Cellcept, Rituxan or other chemotherapeutic treatment presently or within 6 months of screening. Subject is a participant in another research project. Subject has contraindications for either ACTH or MP administration.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ACTH IM monthly<br>Subjects assigned to the ACTH arm will receive ACTH (Acthar gel) as intramuscular (IM) injections once a day for 3 consecutive days on a monthly basis, for 12 consecutive months. The dosage of ACTH will be 80 units per injection, for a total of 240 units over the three day period. | Drug: ACTH<br>* Subjects assigned to the ACTH arm will receive ACTH (Acthar gel) as intramuscular (IM) injections once a day for 3 consecutive days on a monthly basis, for 12 consecutive months. The dosage of ACTH will be 80 units per injection, for a total of 240 units over the three day period.<br>* Other names: Acthar Gel;|
| Active Comparator: MP IV monthly<br>Subjects assigned to the MP arm will receive intravenous (IV) infusions of 1 gram of MP once a month for 12 months. | Drug: Methylprednisolone<br>* Subjects assigned to the MP arm will receive intravenous (IV) infusions of 1 gram of MP once a month for 12 months<br>* Other names: Solumedrol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized Relapse Rate |  | 15 months study: 12 months treatment and 3 months follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Multiple Sclerosis Functional Composite (MSFC), Expanded Disability Status Scale score (EDSS) and Multiple Sclerosis Quality of Life (MSQOL), peripheral blood lymphocytes measure for regulatory immune activities. |  | 15 months: 12 months treatmen and 3 months follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Sclerosis, ACTH, Steroids