Clinical trial NCT02697617: Use of Low Dose Pioglitazone to Treat Autosomal Dominant Polycystic Kidney Disease
Official title: Use of Low Dose Pioglitazone to Treat Autosomal Dominant Polycystic Kidney
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Polycystic Kidney Disease
Lead sponsor: Indiana University
Sponsor class: OTHER
First posted: 2016-03-03
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety: Total Body Water
timeFrame: average of 4 measures in each 12 month arm
measure: Efficacy: Percent Change in Total Kidney Volume
timeFrame: Baseline, end of year 1, and end of year 2
Secondary outcomes:
measure: Safety: Hypoglycemia
timeFrame: measured quarterly for 12 months in pioglitazone and same in placebo
measure: Safety: Elevated Liver Function Tests
timeFrame: measured quarterly over 12 months for each arm
measure: Efficacy: Glomerular Filtration Rate
timeFrame: average of 4 values over 12 months
measure: Efficacy Blood Pressure
timeFrame: average of 4 measures over 12 months
measure: Bone Marrow Fat
timeFrame: Baseline, end of year 1, and end of year 2
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University Health
state: Indiana
Study officials:
affiliation: Indiana University
name: Sharon Moe, 317-944-7580
role: PRINCIPAL_INVESTIGATOR
References: