Metformin as a Novel Therapy for Autosomal Dominant Polycystic Kidney Disease

NCT02656017 | Completed Phase 2 Results DMC

• 2 other identifiers: PRO15060422CDMRP-PR141606
• Study Type: interventional
• Target: 97
• Locations: 1 country
• Sites: 2

Brief Summary

This study will test to see if metformin is safe and if it is tolerated compared to placebo in adult Autosomal Dominant Polycystic Kidney Disease (ADPKD) patients with beginning stages of chronic kidney disease. We will also measure its effect on progression of kidney disease as reflected in the kidney size and the kidney function, along with its effect on kidney pain and quality of life.

Conditions

Polycystic Kidney, Autosomal Dominant

Keywords

kidney disease; polycystic kidney disease; autosomal dominant kidney disease; kidney cysts; PKD

Outcome Measures

Primary Outcomes (3)

• Change in the Gastrointestinal Symptoms Rating Scale (GSRS) to 24 Months

  GSRS is a widely used, validated 15-item questionnaire used to assess GI symptom burden (minimum, maximum: 1, 7, where higher mean score is worse outcome). Mean change to 24 months, estimated with a repeated measures analysis (baseline, 2 weeks, 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 months) using a linear mixed model.

  Baseline, 2 weeks, 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 months

• Drug Tolerability

  Tolerability was based on the first visit a participant responded no to the following question "Can you tolerate this dose of study drug the rest of your life?", which was asked at baseline, 2 weeks, 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 months.

  Baseline, 2 weeks, 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 months

• Rate of Serious Adverse Events (SAE)

  Serious adverse events (SAE) occurring from the time a participant signs the informed consent (at the screening visit) until the end of the study, meeting 1 or more of the criteria of: 1) Resulting in death, 2) Non-elective hospitalization, 3) Life threatening (if patient continued on study drug would result in death), 4) Harming or disabling persistently or permanently , 5) Exceeding the nature, severity or frequency of risk described in the protocol or 6) Resulting in congenital anomaly.

  26 months

Secondary Outcomes (11)

• Quality of Life Physical Component

  Baseline, 1 month, 3 months and every 3 months thereafter to 24 months

• Quality of Life Mental Component

  Baseline, 1 month, 3 months and every 3 months thereafter to 24 months

• Back Pain Frequency Over the Past 3 Months Since Last Visit

  Baseline, 1 month, 3 months and every 3 months thereafter to 24 months

• Estimated Glomerular Filtration Rate (eGFR)

  Baseline, 2 weeks, and 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 months

• Total Kidney Volume From Magnetic Resonance Imaging

  Baseline, 6 months, 12 months, 18 months, 24 months

Study Arms (2)

Metformin

EXPERIMENTAL

Participants will be started on 500 mg of metformin once daily, with the following scheduled dose titrations: * Increase to 500mg twice daily at week 2 * Increase to 1000mg qAM, 500mg qPM at week 4 * Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months). * Increased titrations based on tolerability

Drug: Metformin

Placebo

PLACEBO COMPARATOR

Participants will be started on 500 mg of placebo once daily, with the following scheduled dose titrations: * Increase to 500mg twice daily at week 2 * Increase to 1000mg qAM, 500mg qPM at week 4 * Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months). * Increased titrations based on tolerability

Other: Placebo

Interventions

Metformin DRUG

Monitoring of tolerability and symptoms.

Also known as: Glucophage, Metformin hydrochloride

Metformin

Placebo OTHER

Monitoring of tolerability and symptoms.

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subject has Autosomal Dominant Polycystic Kidney Disease; Subject is fluent in English

You may not qualify if:

• Subject is not on active military duty; Subject is not currently participating in another clinical trial; Subject's current GFR is not \<50 cc/min/1.73m2; Subject does not have diabetes; Subject does not have a systemic disease other than hypertension and PKD; Subject does not have a solitary kidney; Subject does not have an allergy or intolerance to metformin; Subject is not pregnant or lactating or intending to become pregnant within the next three years; Subject does not have an unstable or unclipped cerebral aneurysm; Subject does not have active coronary artery disease; Subject does not have an MRI incompatible device/implant; Subject does not have severe claustrophobia; Subject has not had any solid organ transplant; Subject does not have a Vitamin B12 deficiency; Subject does not currently take any medications that interact with metformin, such as nifedipine, furosemide, cationic drugs (amiloride, ranitidine, triamterene digoxin, procainamide, quinidine, vancomycin, trimethoprim); Subject does not currently take nor has taken (within 2 weeks) the drug tolvaptan (Jynarque or Samsca)

Sponsors & Collaborators

• Kyongtae Ty Bae, M.D., Ph.D.: lead
• Tufts Medical Center: collaborator
• University of Maryland, Baltimore: collaborator
• University of Southern California: collaborator
• United States Department of Defense: collaborator

Study Sites (2)

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Related Publications (3)

• 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

• El-Damanawi R, Stanley IK, Staatz C, Pascoe EM, Craig JC, Johnson DW, Mallett AJ, Hawley CM, Milanzi E, Hiemstra TF, Viecelli AK. Metformin for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2024 Jun 4;6(6):CD013414. doi: 10.1002/14651858.CD013414.pub2.

  PMID: 38837240 DERIVED

• Seliger SL, Watnick T, Althouse AD, Perrone RD, Abebe KZ, Hallows KR, Miskulin DC, Bae KT. Baseline Characteristics and Patient-Reported Outcomes of ADPKD Patients in the Multicenter TAME-PKD Clinical Trial. Kidney360. 2020 Dec 31;1(12):1363-1372. doi: 10.34067/KID.0004002020.

  PMID: 33768205 DERIVED

MeSH Terms

Conditions

Polycystic Kidney, Autosomal Dominant; Kidney Diseases; Polycystic Kidney Diseases

Interventions

Metformin

Condition Hierarchy (Ancestors)

Kidney Diseases, Cystic; 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)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Dr. Kyongtae Bae
• Organization: University of Pittsburgh

baek@upmc.edu

412-647-3500

Study Officials

• Kyongtae Bae, MD, PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 23, 2015
• First Posted: January 14, 2016
• Study Start: June 27, 2016
• Primary Completion: December 7, 2020
• Study Completion: December 7, 2020
• Last Updated: August 9, 2022
• Results First Posted: August 9, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)