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

NCT02697617 | Completed Phase 2 Results DMC

• 2 other identifiers: IndianaU 1308084213FD-R-004826-01-A2
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Polycystic Kidney Disease

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• Safety: Hypoglycemia

  measured quarterly for 12 months in pioglitazone and same in placebo

• Safety: Elevated Liver Function Tests

  measured quarterly over 12 months for each arm

• Efficacy: Glomerular Filtration Rate

  average of 4 values over 12 months

• Efficacy Blood Pressure

  average of 4 measures over 12 months

• Bone Marrow Fat

  Baseline, end of year 1, and end of year 2

Study Arms (2)

Placebo Arm

PLACEBO COMPARATOR

Subject will be on placebo

Drug: Placebo

Pioglitazone Arm

ACTIVE COMPARATOR

Subject will be on pioglitazone

Drug: Pioglitazone

Interventions

Pioglitazone DRUG

Pioglitazone

Also known as: Actos

Pioglitazone Arm

Placebo DRUG

Placebo

Placebo Arm

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Indiana University: lead

Study Sites (1)

Indiana University Health

Indianapolis, Indiana, 46202, United States

Location

Related Publications (1)

• St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.

  PMID: 39356039 DERIVED

MeSH Terms

Conditions

Polycystic Kidney Diseases

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Kidney Diseases, Cystic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Ciliopathies; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

The major limitation is the small sample size.

Results Point of Contact

• Title: Dr. Sharon Moe
• Organization: Indiana University School of Medicine

smoe@iu.edu

317 278 2868

Study Officials

• Sharon Moe, 317-944-7580

  Indiana University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Stuart A. Kleit Professor of Medicine, Director, Division of Nephrology

Study Record Dates

• First Submitted: October 30, 2015
• First Posted: March 3, 2016
• Study Start: January 26, 2016
• Primary Completion: October 1, 2019
• Study Completion: January 1, 2020
• Last Updated: January 15, 2021
• Results First Posted: January 15, 2021

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)