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

Use of Low Dose Pioglitazone to Treat Autosomal Dominant Polycystic Kidney

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.

Study Overview

• Status: Completed
• Conditions: Polycystic Kidney Disease
• Intervention / Treatment: Drug: Placebo; Drug: Pioglitazone

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Arm; Subject will be on placebo	Drug: Placebo; Placebo
Active Comparator: Pioglitazone Arm; Subject will be on pioglitazone	Drug: Pioglitazone; Pioglitazone; Other Names: Actos

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Indiana University
• Investigators: Principal Investigator: Sharon Moe, 317-944-7580, Indiana University

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2016
• Primary Completion (Actual): October 1, 2019
• Study Completion (Actual): January 1, 2020

Study Registration Dates

• First Submitted: October 30, 2015
• First Submitted That Met QC Criteria: February 26, 2016
• First Posted (Estimate): March 3, 2016

Study Record Updates

• Last Update Posted (Actual): January 15, 2021
• Last Update Submitted That Met QC Criteria: December 22, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Abnormalities, Multiple; Kidney Diseases, Cystic; Ciliopathies; Kidney Diseases; Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant; Hypoglycemic Agents; Physiological Effects of Drugs; Pioglitazone
• Other Study ID Numbers: IndianaU 1308084213; FD-R-004826-01-A2 (Other Identifier: FDA Orphan Products Development Ad Hoc Panel Review)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No