Pioglitazone in Early Parkinson's Disease
Condition: Parkinson's Disease
MeSH terms: Parkinson Disease
Intervention: Pioglitazone; placebo
Intervention description: Oral capsules of Pioglitazone (15 mg capsules) either 15 mg/qd or 45 mg/qd
Subjects will titrate in a blinded fashion to 30 mg/day after 2 weeks and to 45 mg per day) 2 weeks later as tolerated.; Placebo will contain microcrystalline cellulose. An over-encapsulation process will be conducted in accordance with Clinical Good Manufacturing Procedures (cGMP) regulations to create a dosage form for the active study drug that will be indistinguishable from the comparator (Placebo) capsule.
Intervention MeSH terms: Pioglitazone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 210.0
Sex: All
Minimum age: 30 Years
Healthy volunteers: No
Keywords: Parkinson's Disease; Biomarkers

Summary:

      This is a multi-center, double-blind, placebo controlled clinical trial of two dosages of
      oral pioglitazone (15 milligram(mg) and 45 milligram (mg)) for safety, tolerability, and
      futility.

      Subjects who are on stable dose of rasagiline 1 mg/day or selegiline 10 mg/day for at least 8
      weeks but no more than 8 months, will be randomized to one of two dosages of oral
      pioglitazone (15 mg and 45 mg) or matching placebo.

      The study will measure disease progression by the change in total Unified Parkinson's Disease
      Rating Scale (UPDRS) score between the baseline visit and 44 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Willing and able to give informed consent.

          2. Men and women with idiopathic PD of less than 5 years duration from diagnosis with a
             Hoehn and Yahr Stage < 2.

          3. On stable dosage of rasagiline 1 mg/day or selegiline 10 mg/day for at least 8 weeks
             but not more than 8 months prior to baseline. Expected to remain on stable dose of
             rasagiline or selegiline as the only treatment for their PD for the duration of the
             study (44 weeks).

          4. Diagnosis must be confirmed by bradykinesia plus one of the other cardinal signs
             (resting tremor, rigidity) being present, without any other known or suspected cause
             of parkinsonism. The clinical signs must be asymmetric.

          5. Subjects may be taking stable doses (30 days) of anticholinergics or creatine (<
             5gm/day) but must be expected to remain on the same dose.

          6. Age > 30 years.

          7. Women who are not postmenopausal or surgically sterile must use a medically accepted
             contraceptive regimen for at least 60 days before the baseline visit, and agree to
             continue such use throughout the duration of the study and for 30 days after the final
             dose of study drug.

        Exclusion Criteria:

          1. Exposure to dopaminergic PD therapy or amantadine within 60 days prior to baseline
             visit or for 90 days or more at any point in the past

          2. Use of any of the following drugs within 180 days prior to baseline: neuroleptics,
             metoclopramide, alpha-methyldopa, clozapine, olanzapine and flunarizine.

          3. Use of any of the following drugs within 90 days prior to baseline: methylphenidate,
             cinnarizine, reserpine, tetrabenazine, amphetamine or monoamine oxidase (MAO)-A
             inhibitors (pargyline, phenelzine, and tranylcypromine).

          4. Presence of drug-induced parkinsonism (e.g., metoclopramide, flunarizine), metabolic
             identified neurogenetic disorders (e.g., Wilson's disease), encephalitis, or other
             atypical Parkinsonian syndromes (e.g., progressive supranuclear palsy, multiple system
             atrophy).

          5. Participation in other drug studies or receipt of other investigational drugs within
             30 days prior to baseline or during the study.

          6. Presence of freezing.

          7. Any clinically significant psychiatric or medical condition or laboratory abnormality,
             which would in the judgment of the Investigator interfere with the subject's ability
             to participate.

          8. History of stereotaxic brain surgery for PD

          9. Clinically significant structural brain disease that the investigator believes would
             interfere with study evaluations.

         10. History of congestive heart failure.

         11. Use of pioglitazone or rosiglitazone within 90 days before randomization.

         12. Known intolerance to pioglitazone or rosiglitazone.

         13. Allergy to rasagiline or selegiline, or contraindication to rasagiline or selegiline
             use.

         14. Type I or Type II diabetes mellitus.

         15. HgbA1C greater than or equal to 6% at Screening.

         16. Known liver disease or elevation of AST or ALT greater than 2.5 times the upper limit
             of normal.

         17. Known history of osteoporosis. All women ≥ 65 years of age or men and woman at high
             risk of osteoporosis should have documented evidence of screening for osteoporosis.
             Factors associated with high risk of osteoporosis include: previous non traumatic
             fracture, chronic glucocorticoid use, body weight under 58 kg, family history of hip
             fracture, current cigarette smoking, and excessive alcohol intake.

         18. Drug or alcohol use or dependence that, in the opinion of the Investigator, would
             interfere with the safe conduct of the study.

         19. Significant peripheral edema (2+ or more) of the extremities of any etiology.

         20. Current or planned use of gemfibrozil or rifampin during the trial.

         21. History of bladder cancer.

         22. Evidence of hematuria which has not been evaluated for evidence of bladder cancer.
             (Documentation of work up or a repeat urine test that was negative for hematuria and
             the primary care physician or urologist does not feel that further work up is
             required.)

         23. History of macular edema.