Use of Low Dose Pioglitazone to Treat Autosomal Dominant Polycystic Kidney Disease

Phase 2

Completed

Brief Summary: Funding Source - FDA OOPD

Pioglitazone is currently used in clinical practice to treat diabetes and this study will examine the potential use of a low dose of the same drug for the treatment of polycystic kidney disease. The purpose of this study is to determine whether the diabetes drug pioglitazone (Actos) is a safe and effective treatment of autosomal dominant polycystic kidney disease when treated in its early stages. Pioglitazone is approved by the FDA for the treatment of diabetes. Pre-clinical models of polycystic kidney disease have shown that low dose treatment with pioglitazone decreases the growth of the cysts. The studies also suggest that effective pioglitazone dosing for polycystic kidney disease may be lower than that used to treat diabetes. The purpose of this study is to see if pioglitazone might slow cyst disease in humans.

Detailed Description: Patients will be randomize to placebo or 15 mg pioglitazone for 12 months, and then be crossed over to the other arm. Patients will undergo MRI of the liver and kidney and MRspectroscopy of the lumbar spine (if they choose as this is ancillary study) three times during the study. Assessments will be every 3 months and include blood work, blood pressure, and body water assessments.

Recruitment & Eligibility

Inclusion Criteria

Male or female patients with autosomal dominant polycystic kidney disease (ADPKD) aged 18-55
estimate glomerular filtration rate (GFR) at or above ≥ 50 ml/min/1.73 m2 by any GFR formula
Normal liver enzymes (ALT/AST)
fasting blood glucose between 70 and120
for female patients, a willingness to use double contraception to avoid pregnancy while in study
able to give informed consent
In the opinion of the investigator, high likelihood of progressive kidney disease

Exclusion Criteria

diabetes, defined as any of the following: fasting blood sugar > 130 times two, HgbA1C > 7, on any blood sugar lowering medication, or past diagnosis of diabetes not occurring during pregnancy
uncontrolled hypertension as determined by the examining physician
history of impaired systolic function (ejection fraction < 50%) by previous echocardiogram or known ischemic cardiovascular disease
findings suggestive of a kidney disease other than ADPKD
systemic illness requiring immunosuppressive or anti-inflammatory agents
congenital absence of a kidney or history of a total nephrectomy
history of cyst reduction or partial nephrectomy
history of renal cyst aspiration within the previous year
History of bladder cancer, or gross hematuria
inability to undergo MRI due to implantable devices or foreign objects that preclude MRI
active renal transplant
allergy or sensitivity to any of the components of the test materials
institutionalized
currently pregnant or plans to become pregnant during the study

Arm && Interventions

Group	Intervention	Description
Placebo Arm	Placebo	Subject will be on placebo
Pioglitazone Arm	Pioglitazone	Subject will be on pioglitazone

Primary Outcome Measures

Name	Time	Method
Safety: Total Body Water	average of 4 measures in each 12 month arm	Bioimpedance analysis (BIA)(Ohms); Increase in BIA in Ohms indicates a decrease in total body water
Efficacy: Percent Change in Total Kidney Volume	Baseline, end of year 1, and end of year 2	Change in total kidney volume by Magnetic Resonance Imaging (MRI) from beginning to end of the 12 months

Secondary Outcome Measures

Name	Time	Method
Safety: Elevated Liver Function Tests	measured quarterly over 12 months for each arm	Number of patients with elevated liver test (ALT or AST) \> 2 times upper limit of normal
Safety: Hypoglycemia	measured quarterly for 12 months in pioglitazone and same in placebo	number of patients with blood sugar \< 70 mg/dl
Efficacy: Glomerular Filtration Rate	average of 4 values over 12 months	average estimated glomerular filtration rate by chronic kidney disease (CKD) epidemiologic (epi) formula measured quarterly
Efficacy Blood Pressure	average of 4 measures over 12 months	mean systolic and diastolic blood pressure
Bone Marrow Fat	Baseline, end of year 1, and end of year 2	We will assess change in bone marrow fat by MR spectroscopy as an ancillary study to be done at the same time as MRI; will not be done due to person leaving institution.