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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Use of Low Dose Pioglitazone to Treat Autosomal Dominant Polycystic Kidney

Conditions
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Polycystic Kidney Disease

Intervention / Treatment
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* Drug: Pioglitazone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Arm<br>Subject will be on placebo | Drug: Placebo<br>* Placebo<br>|
| Active Comparator: Pioglitazone Arm<br>Subject will be on pioglitazone | Drug: Pioglitazone<br>* Pioglitazone<br>* Other names: Actos;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Hypoglycemia | number of patients with blood sugar < 70 mg/dl | measured quarterly for 12 months in pioglitazone and same in placebo | 
| Safety: Elevated Liver Function Tests | Number of patients with elevated liver test (ALT or AST) > 2 times upper limit of normal | measured quarterly over 12 months for each arm | 
| Efficacy: Glomerular Filtration Rate | average estimated glomerular filtration rate by chronic kidney disease (CKD) epidemiologic (epi) formula measured quarterly | average of 4 values over 12 months | 
| Efficacy Blood Pressure | mean systolic and diastolic blood pressure | average of 4 measures over 12 months | 
| Bone Marrow Fat | 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. | Baseline, end of year 1, and end of year 2 |