Augmenting Cerebral Blood Flow to Treat Established Multiple Sclerosis
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Intervention: Acetazolamide; Placebo
Intervention description: see arm description; Placebo arm
Intervention MeSH terms: Acetazolamide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Two phase design: phase 1, patients randomized to ACZ or placebo and followed for 24 weeks; phase 2, patients that received placebo in phase 1 switch to ACZ (delayed-start group) and patients that received ACZ in phase 1 continue on ACZ (ACZ-ACZ group)
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No
Keywords: Acetazolamide; Lesions; Neurodegeneration; Repair

Summary:

      This study will evaluate how improved cerebral blood flow affects the way in which newly
      formed MS lesions evolve and whether tissue repair is improved. Patients with multiple
      sclerosis (MS) will be treated with acetazolamide in daily divided doses and obtain MRI to
      determine how much and in which regions of the brain cerebral perfusion improves as well as
      the extent to which tissue integrity is improved in these areas.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Diagnosis of relapsing forms of multiple sclerosis using revised McDonald criteria

          2. Stable on any FDA-approved disease-modifying therapy. The term "stable" implies that
             the subject has not had change in therapy for any reason for the 6 months prior to
             study entry.

          3. Expanded Disability Status Scale (EDSS) score of 0-6.0 inclusive

          4. Understood and signed written informed consent, obtained prior to the study subject
             undergoing any study related procedure, including screening tests.

        Exclusion Criteria:

          1. Known hypersensitivity to sulfonamides or derivatives

          2. Known history of renal or hepatic disease, cerebrovascular disease including stroke,
             transient ischemic attack, myocardial infarction, angina or congestive heart failure.

          3. Evidence to suggest hyponatremia or hypokalemia, marked kidney dysfunction defined as
             creatinine greater than 2.0 mg/dL or liver disease dysfunction defined as aspartate
             aminotransferase (AST) or alanine aminotransferase (ALT) greater than three-fold upper
             limit of normal (ULN).

          4. Evidence to suggest suprarenal gland failure.

          5. Evidence of hyperchloremic acidosis.

          6. Initiation of new immunosuppressant treatment after the subject becomes
             protocol-eligible (except for corticosteroids) or enrollment in a concurrent trial.

          7. Prior treatment with mitoxantrone, natalizumab, methotrexate, cladribine
             cyclophosphamide or other change in disease modifying therapy (DMT) within 6 months of
             initiation of study.

          8. Subjects with any history of cytopenia.

          9. History of pulmonary obstruction or emphysema.

         10. Active hepatitis B or hepatitis C infection or evidence of cirrhosis.

         11. Human immunodeficiency virus (HIV) positivity.

         12. Uncontrolled diabetes mellitus defined as HbA1c>8% and/or requiring intensive
             management.

         13. Uncontrolled viral, fungal, or bacterial infection (excluding asymptomatic
             bacteriuria).

         14. Any condition that, in the opinion of the investigators, would jeopardize the ability
             of the subject to tolerate treatment with ACZ.

         15. Prior history of malignancy.

         16. Positive pregnancy test or inability or unwillingness to use effective means of birth
             control. Effective birth control defines as:

               -  Refraining from all acts of vaginal intercourse (abstinence)

               -  Consistent use of birth control pills

               -  Tubal sterilization or male partner who has undergone vasectomy

               -  Placement of an intrauterine device (IUD)

               -  Use, with every act of intercourse, of a diaphragm with contraceptive jelly
                  and/or condoms with contraceptive foam

         17. Presence of metallic objects implanted in the body that would preclude the ability of
             the subject to safely have MRI exams.

         18. Psychiatric illness, mental deficiency, or cognitive dysfunction making compliance
             with treatment of informed consent impossible.