Pilot Test of ACTOS in Multiple Sclerosis: Safety and Tolerability
Condition: Multiple Sclerosis, Relapsing-Remitting
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to determine whether an already FDA approved drug is safe and
      tolerable in Relapsing Remitting Multiple Sclerosis patients.
    

Detailed description: 
      1. Current treatments for Multiple Sclerosis (MS) only partially reduce the relapse rate or
           improve symptoms, have to be injected, and have side effects. In animal models of MS,
           the FDA-approved oral anti-diabetic drug ACTOS prevented and reduced symptoms. ACTOS has
           a good safety profile in diabetics and healthy volunteers, but it's effects in MS are
           not known. This trial will test the safety of taking daily ACTOS in Relapsing Remitting
           MS (RRMS) patients, the most common form of MS. Subjects will take ACTOS or a non active
           pill (placebo) every day, and during the trial the safety of the drug will be tested by
           doing blood tests for certain enzymes related to liver function, for glucose levels, by
           having the blood pressure measured, and having other routine laboratory blood tests
           carried out. The safety of ACTOS on MS disease will be tested by doing neurological
           examinations, Magnetic Resonance Imaging (MRI, a method which gives an image of the
           damage MS causes in brain), and other blood tests to make sure that the MS symptoms are
           not made worse by ACTOS. Findings that ACTOS is safe and tolerated in RRMS patients will
           help provide the basis for designing Phase II trials.

        2. Subjects will be selected who have been diagnosed with RR-MS and who are taking the drug
           Avonex or Rebif to treat their MS symptoms. Subjects will be randomized to receive
           either ACTOS (30 mg) or a non-active tablet (placebo). Both the subjects and the
           investigator will be blinded meaning no-one will know which pill they are given. The
           subjects will take one pill daily by mouth for up to 18 months, the length of the trial.
           During the trial, subjects will be examined 8 times. At each visit about 3 tablespoons
           (30cc) of blood will be taken for tests. Subjects will have a total of 3 MRI scans done
           during the trial (at months 0, 5, and 12) to test if ACTOS effects the number or size of
           plaques in brain. At each visit the subjects will also have vital signs checked, and a
           urine pregnancy test performed

        3. ACTOS can cause fluid retention which may cause or increase the risk of heart damage.
           ACTOS can cause mild weight gain or anemia (low hemoglobin levels). ACTOS can cause mild
           hypoglycemia (low blood sugar levels). ACTOS can increase ovulation and increase risk of
           pregnancy. Since ACTOS is structurally related to Troglitazone, which was associated
           with liver damage and rare cases of liver failure, patients treated with ACTOS are
           carefully monitored for changes in liver enzyme levels. In other studies with ACTOS, the
           most common side effects were upper respiratory tract infections, sinusitis, muscle
           pain, tooth disorder, sore throat, headache and gas. ACTOS may have other side effects,
           such as heartburn, diarrhea, constipation, dizziness, abdominal fullness, nausea, and
           loose stools.

           MRI is a FDA approved safe procedure. Possible risks include feelings of anxiety or
           claustrophobia, or disturbance by noise made during the procedure. A safe contrast agent
           (gadolinium) will be used for MRI. Injection and insertion of the needle may cause minor
           pain, bruising, and/or infection at the injection site. Gadolinium may cause brief
           discomfort, tingling, or warmth in the lips, or metallic taste in the mouth, tingling in
           the arm, nausea, or headache. Very rarely, there may be an allergic reaction. A standard
           questionnaire will be used to determine the safety for each patient before an MRI.

           Blood sample collection has risks of edema, swelling, or infection at the site of
           withdrawal.

           We will discuss all of the above in the consent form as outlined in the form with the
           candidates.

        4. There are no known benefits from participating in this trial; however the knowledge
           gained may benefit others in the future.

        5. This trial will recruit 30 RR MS patients. Approximately 10 male and 20 female patients
           will be recruited, with about equal numbers coming from the UIC and Rush. Patients can
           be between the ages of 18-64 yrs, and will be obtained from outpatient clinics. Consent
           process will follow standardized forms.
    

Intervention name(s): ACTOS (Pioglitazone)
Intervention type(s): Drug
Intervention MeSH terms: Pioglitazone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment
Keywords: Multiple Sclerosis; Relapsing, Remitting; Autoimmune disease