Safety and Tolerability of ISX (Isoxsuprine HCL) in MS Relapses
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This is a proof of concept, randomized, double-blind, placebo-controlled, 2-arm, parallel
      group study of Isoxsuprine in MS subjects experiencing a typical relapse.

      Evidence from preclinical stroke models and experimental allergic encephalomyelitis suggest
      that isoxsuprine hydrochloride may have neuroprotective activity and reduce disability in
      animal models. Given its potential neuroprotective effects in CNS injury models, the
      investigators propose to test it as a safe, tolerable add on treatment for acute relapses in
      patients with relapsing forms of MS.
    

Detailed description: 
      This is a proof of concept, randomized, double-blind, placebo-controlled, 2-arm, parallel
      group study of Isoxsuprine in MS subjects experiencing a typical relapse.

      All subjects will have a documented diagnosis of relapsing MS or a clinically isolated
      syndrome by international criteria. The relapse will be of sufficient severity that their
      physician recommends treatment with a high dose corticosteroid pulse. All subjects will have
      a physical examination and history with questions on drug sensitivities. Subjects
      experiencing the onset of objective neurological deficits consistent with relapse within 7
      days of randomization are eligible for screening for this study. Those currently on MS
      disease modifying therapy will have received a stable regimen of the medications for at least
      30 days prior to screening and will continue the same doses and regimens for the duration of
      their study participation.

      Consented subjects will be assessed for relapse criteria and those who meet study eligibility
      criteria and agree to be treated with a standard 3 to 5 day pulse of high dose
      corticosteroids, will be randomized with equal probability to 1 of 2 treatment groups:
      placebo capsule or active Isoxsuprine (ISX).

      The Screening Visit will take place within 7 days of relapse onset and within 48 hours of
      initiating high dose steroids. Subjects may start corticosteroids anytime during this 7 day
      window. During the screening period, subjects will be assessed with the Expanded Disability
      Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and cognitive testing
      prior to treatment with ISX or placebo (1:1 ratio). Safety Assessments during screening will
      include a physical exam, electrocardiogram, vital signs, weight and a urine pregnancy test
      for females of child bearing potential. At 7 (± 1) days following the completion of the 5-day
      ISX dosing, subjects will be re-assessed with the EDSS.

      Subjects will be evaluated for treatment response using the EDSS and other standard measures.

      Study drug will be administered as one (1) 10 mg capsule, 3 times daily for 5 days in
      conjunction with concomitant dosing with high dose corticosteroids. This can be any accepted
      regimen, including daily iv methylprednisolone 1000 mg/day or 600mg oral prednisone two times
      a day at approximately 8AM and noon, with food, as typically provided by UNM MS Specialty
      Clinic.
    

Intervention name(s): Isoxsuprine Hydrochloride; Placebo; Corticosteroid
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Compounded Isoxsuprine hydrochloride capsules; Identical microcrystalline cellulose placebo manufactured to mimic Isoxsuprine Hydrochloride 10 MG capsules; This can be any accepted regimen, including daily iv methylprednisolone 1000 mg/day or 600mg oral prednisone two times a day at approximately 8AM and noon
Other intervention name(s): Duvadilan; Methylprednisolone; Prednisone
Intervention MeSH terms: Prednisone; Methylprednisolone; Isoxsuprine
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This is a proof of concept, randomized, double-blind, placebo-controlled, 2-arm, parallel group study of Isoxsuprine in MS subjects experiencing a typical relapse
Masking: Double (Participant, Investigator)
Primary purpose: Treatment