Pioglitazone in Early Parkinson's Disease

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.