Implementation of Metformin theraPy to Ease Decline of Kidney Function in Polycystic Kidney Disease (IMPEDE-PKD)

March 26, 2026 updated by: The University of Queensland

Implementation of Metformin theraPy to Ease Decline of Kidney Function in Polycystic Kidney Disease (IMPEDE-PKD): A Randomised Placebo-Controlled Trial

This study will investigate if a medication (metformin) widely used in the treatment of diabetes could be re-purposed for the treatment of patients with a diagnosis of early stage ADPKD to slow the rate of kidney function decline, reducing morbidity and mortality and improving the quality of life for ADPKD patients.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Autosomal Dominant Polycystic Kidney Disease (ADPKD) affects 12.5 million people worldwide and is the 4th leading cause of kidney failure. Cyst growth begins in childhood, and over decades leads to painful kidneys, hypertension and chronic kidney disease. ADPKD patients also have a high prevalence of anxiety, depression and poor quality of life. Despite this enormous burden, there is a lack of evidence for therapies and affordable, effective treatment options. To date, only one disease modifying therapy is licensed for use in ADPKD (tolvaptan), but it is limited by its restricted availability, side effects and high cost. Metformin, an inexpensive and familiar drug, has been shown in previous studies to target cyst-forming signals, thereby slowing the cyst growth rate. IMPEDE-PKD is an Australian-led global Phase III randomised controlled trial to investigate the effect of metformin on ADPKD disease progression. The study will recruit a total of 1,174 adult ADPKD patients from around the world (250 from Australia). The outcomes of this research will identify effective and targeted therapies for ADPKD that will slow kidney function decline, reduce the impact of the illness and likelihood of death, and improve the quality of life for ADPKD patients and families.

Study Type

Interventional

Enrollment (Estimated)

1174

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Australia
    • New South Wales
      • Gosford, New South Wales, Australia, 2250
        • Active, not recruiting
        • Renal Research
      • Sydney, New South Wales, Australia, 2050
        • Active, not recruiting
        • Royal Prince Alfred Hospital
      • Sydney, New South Wales, Australia, 2145
        • Active, not recruiting
        • Westmead Hospital - Western Sydney Local Health District
      • Sydney, New South Wales, Australia, 2065
        • Active, not recruiting
        • Royal North Shore Hospital
    • Queensland
      • Bundaberg, Queensland, Australia, 4670
        • Active, not recruiting
        • Bundaberg Hospital
      • Douglas, Queensland, Australia, 4814
        • Active, not recruiting
        • Townsville University Hospital
      • Herston, Queensland, Australia, 4006
        • Active, not recruiting
        • Royal Brisbane and Women's Hospital
      • Woolloongabba, Queensland, Australia, 4102
        • Active, not recruiting
        • Princess Alexandra Hospital
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Active, not recruiting
        • Royal Adelaide Hospital
    • Victoria
      • Melbourne, Victoria, Australia, 3084
        • Active, not recruiting
        • Austin Health
      • Melbourne, Victoria, Australia, 3052
        • Active, not recruiting
        • Royal Melbourne Hospital
      • Melbourne, Victoria, Australia, 3168
        • Active, not recruiting
        • Monash Medical Centre
    • Western Australia
      • Perth, Western Australia, Australia, 6009
        • Active, not recruiting
        • Sir Charles Gairdner Hospital
  • New Zealand
      • Palmerston North, New Zealand
    • Bay of Plenty
      • Tauranga, Bay of Plenty, New Zealand, 3112
        • Recruiting
        • Te Whatu Ora - Hauora a Toi Bay of Plenty
        • Contact:
        • Principal Investigator:
          • Scott Crawford, Dr
    • Northland
      • Whangārei, Northland, New Zealand, 0110
        • Recruiting
        • Te Whatu Ora - Te Tai Tokerau
        • Principal Investigator:
          • Adam Mullan, Dr
        • Contact:
    • Otago
      • Dunedin, Otago, New Zealand, 9016
        • Recruiting
        • Te Whatu Ora - Southern
        • Contact:
        • Principal Investigator:
          • Rob Walker, Professor
    • Taranaki Region
      • New Plymouth, Taranaki Region, New Zealand, 4310
        • Recruiting
        • Te Whatu Ora - Taranaki
        • Contact:
        • Principal Investigator:
          • Mahmoud Amer, Dr
  • United Kingdom
      • Cardiff, United Kingdom
        • Recruiting
        • Cardiff and Vale University Health Board
        • Contact:
          • Mat Davies, Dr
      • Carshalton, United Kingdom
        • Recruiting
        • Epsom and St Helier University Hospitals
        • Contact:
          • Ayesha Irtiza-Ali, Dr
      • London, United Kingdom, NW3 2QG
        • Not yet recruiting
        • Royal Free Hospital
        • Contact:
          • Daniel Gale, Dr
        • Principal Investigator:
          • Daniel Gale, Dr
      • London, United Kingdom, SE5 9RS
        • Not yet recruiting
        • King's College Hospital
        • Contact:
          • Adam Rumjon, Dr
        • Principal Investigator:
          • Adam Rumjon, Dr
      • London, United Kingdom, E1 1FR
        • Not yet recruiting
        • The Royal London Hospital
        • Contact:
          • Conor Byrne, Dr
        • Principal Investigator:
          • Conor Byrne, Dr
      • London, United Kingdom
        • Recruiting
        • St George'S University Hospital
        • Contact:
          • Daniel Jones, Dr
      • Nottingham, United Kingdom
        • Recruiting
        • Nottingham University Hospital
        • Contact:
          • Matthew Hall, Dr
      • Plymouth, United Kingdom
        • Recruiting
        • University Hospitals Plymouth NHS Trust
        • Contact:
          • Kris Houlberg, Dr
      • Stevenage, United Kingdom
        • Recruiting
        • East & North Hertfordshire Teaching NHS Trust
        • Contact:
          • Sivakumar Sridharan, Dr
      • Sunderland, United Kingdom
        • Recruiting
        • South Tyneside and Sunderland NHS Foundation Trust
        • Contact:
          • Shalabh Srivastava, Dr
      • York, United Kingdom
        • Recruiting
        • York and Scarborough Teacehing Hospitals
        • Contact:
          • Colin Jones, Dr
    • Devon
      • Exeter, Devon, United Kingdom, EX2 5DW
        • Recruiting
        • Royal Devon & Exeter Hospital
        • Contact:
          • Rhian Clissold, Dr
        • Principal Investigator:
          • Rhian Clissold, Dr
    • East Midlands
      • Nottingham, East Midlands, United Kingdom, NG5 1PB
        • Not yet recruiting
        • Nottingham Renal Unit, Nottingham City Hospital
        • Contact:
          • Matt Hall, Dr
        • Principal Investigator:
          • Matt Hall, Dr
    • Inverness Shire
      • Inverness, Inverness Shire, United Kingdom, IV2 3UJ
        • Not yet recruiting
        • Raigmore Hospital
        • Contact:
          • Stewart Lambie, Dr
        • Principal Investigator:
          • Stewart Lambie, Dr
    • Lancashire
      • Preston, Lancashire, United Kingdom, PR2 9HT
        • Not yet recruiting
        • Royal Preston Hospital
        • Contact:
          • Aimun Ahmed, Dr
        • Principal Investigator:
          • Aimun Ahmed, Dr
      • Salford, Lancashire, United Kingdom, M6 8HD
        • Recruiting
        • Salford Royal Hospital
        • Principal Investigator:
          • Aine DeBhalis, Dr
        • Contact:
          • Grahame Wood, Dr
    • Leicestershire
      • Leicester, Leicestershire, United Kingdom, LE5 4PW
        • Recruiting
        • Leicester General Hospital
        • Contact:
          • Osasuyi Iyasere, Dr
        • Principal Investigator:
          • Osasuyi, Iyasere, Dr
    • London
      • Carshalton, London, United Kingdom, SM5 1AA
        • Not yet recruiting
        • St Helier Hospital
        • Contact:
          • Ayesha Irtiza-Ali, Dr
        • Principal Investigator:
          • Ayesha Irtiza-Ali, Dr
    • Merseyside
      • Liverpool, Merseyside, United Kingdom, L9 7AL
        • Recruiting
        • Aintree University Hospital
        • Contact:
          • Chris Goldsmith, Dr
        • Principal Investigator:
          • Chris Goldsmith, Dr
    • Norfolk
      • Norwich, Norfolk, United Kingdom, NR4 7UY
        • Not yet recruiting
        • Norfolk and Norwich University Hospital
        • Contact:
          • Matt Todd, Dr
        • Principal Investigator:
          • Matt Todd, Dr
    • Northern Ireland
      • Antrim, Northern Ireland, United Kingdom, BT41 2RL
        • Recruiting
        • Antrim Area Hospital
        • Contact:
          • Stephanie Bolton, Dr
        • Principal Investigator:
          • Stephanie Bolton, Dr
      • Belfast, Northern Ireland, United Kingdom, BT16 1RH
        • Recruiting
        • Ulster Hospital
        • Contact:
          • Alastair Woodman, Dr
        • Principal Investigator:
          • Alastair Woodman, Dr
      • Londonderry, Northern Ireland, United Kingdom, BT47 6SB
        • Recruiting
        • Altnagelvin Hospital
        • Contact:
          • Frank McCarroll, Dr
        • Principal Investigator:
          • Frank McCarroll, Dr
      • Newry, Northern Ireland, United Kingdom, BT35 8DR
        • Not yet recruiting
        • Daisy Hill Hospital
        • Contact:
          • Neal Morgan, Dr
        • Principal Investigator:
          • Neal Morgan, Dr
    • Oxfordshire
      • Oxford, Oxfordshire, United Kingdom, OX3 7LE
        • Recruiting
        • Oxford Kidney Unit, Churchill Hospital,
        • Contact:
          • Tom Connor, Dr
        • Principal Investigator:
          • Tom Connor, Dr
    • South Yorkshire
      • Doncaster, South Yorkshire, United Kingdom, DN2 5LT
        • Recruiting
        • Doncaster Royal Infirmary
        • Contact:
          • Mohsen El Kossi, Dr
        • Principal Investigator:
          • Mohsen El Kossi, Dr
      • Sheffield, South Yorkshire, United Kingdom, S5 7AU
        • Recruiting
        • Sheffield Kidney Institute
        • Contact:
          • Ragada El-Damanawi, Dr
        • Principal Investigator:
          • Ragada El-Damanawi, Dr
    • Staffordshire
      • Stoke-on-Trent, Staffordshire, United Kingdom, ST4 6QG
        • Not yet recruiting
        • Royal Stoke University Hospital
        • Contact:
          • Dominic De Takats, Dr
        • Principal Investigator:
          • Dominic De Takats, Dr
    • Tyne and Wear
      • Newcastle upon Tyne, Tyne and Wear, United Kingdom, NE7 7DN
        • Not yet recruiting
        • Freeman Hospital
        • Contact:
          • John Sayer, Dr
        • Principal Investigator:
          • John Sayer, Dr
    • West Midlands
      • Birmingham, West Midlands, United Kingdom, B15 2GW
        • Not yet recruiting
        • Queen Elizabeth Hospital Birmingham
        • Contact:
          • Yuki Heath, Dr
        • Principal Investigator:
          • Yuki Heath, Dr
    • West Yorkshire
      • Bradford, West Yorkshire, United Kingdom, BD5 0NA
        • Recruiting
        • Bradford Renal Unit, St Luke's Hospital
        • Contact:
          • Mohd Furqan, Dr
        • Principal Investigator:
          • Mohd Furqan, Dr

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

To be eligible to participate in this trial, patients must satisfy all of the following inclusion criteria:

  1. Willing to participate and provide informed consent
  2. Aged 18-70 years
  3. Diagnosis of ADPKD based on radiological +/- genetic criteria as per Kidney Health Australia - Caring for Australians and New Zealanders with Kidney Impairment (KHA-CARI) Guidelines
  4. eGFR equal to or greater than 38 mL/min/1.73m2 and <90 mL/min/1.73m2

And have either:

5(a) One or more risk factors of progression from the following:

  • Bilateral kidney length equal to or greater than16.5 cm, or
  • Total Kidney Volume (TKV) equal to or greater than 750 mL or height-adjusted TKV (htTKV) equal to or greater than 600 mL/m2, or
  • Mayo class IC/D/E or Pro-PKD score equal to or greater than 6 OR 5(b) Evidence of Active progression
  • Decline in eGFR equal to or greater than 5 mL/min/1.73m2 in one year, or
  • Decline in eGFR equal to or greater than 3 mL/min/1.73m2 per year over five years or more. or
  • Increase in htTKV/TKV of equal to or greater than 5% per year on at least 2 measurements in the past year, excluding any initial eGFR effect over the initial 3 months of tolvaptan commencement (if applicable) Note: Tolvaptan therapy must have been in place for at least 6 months with stable dose for at least 3 months.

Exclusion Criteria:

  1. Diabetes mellitus (as per American Diabetes Association definition), or other systemic conditions that may cause CKD independent of PKD (excluding hypertension)
  2. Uncontrolled hypertension (Systolic BP >160 mmHg and/or diastolic BP >100 mmHg after a period of rest)
  3. Clinically significant heart failure, including but not limited to New York Heart Association Class (NYHA) III or IV

  4. Non-polycystic liver disease, including but not limited to:

    1. Liver enzymes (ALT, AST or Total Bilirubin) >2 times the upper limit of normal, except when a diagnosis of Gilbert Syndrome exists and/or,
    2. Child-Pugh classification score equal to or greater than 5
  5. Any contraindication to metformin including abnormal liver function tests or untreated Vitamin B12 deficiency
  6. Currently taking metformin
  7. Pregnancy or breastfeeding, or planning to get pregnant in the next three years.
  8. Comorbidities with potential to contaminate trial outcomes, specifically active cancer, history of other solid organ transplantations, active chronic obstructive pulmonary disease (COPD), active inflammatory bowel disease, and the presence of stoma.
  9. History of dialysis.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Control
Participants randomised to the control group receive placebo plus standard of care for 104 weeks.
Other: Control
Placebo is inactive tablets that is identical to the intervention Metformin tablets.
Other Names:
  • Placebo
Experimental: Intervention

Participants randomised to the intervention group receive Metformin XR plus standard of care for 104 weeks.

Dosage will depend on individual participant's level of tolerance to Metformin XR as well as their estimated glomerular filtration rate (eGFR). The dosage will be between 500-2000mg/day.
Drug: Metformin XR
Extended release metformin.
Other Names:
  • APO-Metformin XR (500mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The change in estimated glomerular filtration rate (eGFR)
Time Frame: Over 24 months
This will be measured using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula at 104 weeks (24 months) from first dispensing date.
Over 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Annualised slope of eGFR.
Time Frame: Over 24 months
The mean rate of change in eGFR from baseline over 2 years, estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula from the serum creatinine concentration analysed in the central laboratory.
Over 24 months
Composite outcome
Time Frame: Over 24 months
A composite outcome comprising a reduction from baseline eGFR of equal to or greater than 30%, kidney failure (defined as an eGFR <15 millilitres/min/1.73m2), and all-cause mortality.
Over 24 months
Severity of change in eGFR
Time Frame: Over 24 months
The proportion of participants with a reduction from baseline in their eGFR of equal to or greater than 30%.
Over 24 months
Kidney failure
Time Frame: Over 24 months
The proportion of participants who experience kidney failure, defined as an eGFR <15mL/min/1.73m2.
Over 24 months
Mortality
Time Frame: Over 24 months
The proportion of participants who die during the observation period, irrespective of the cause.
Over 24 months
Change in medication dosage during the trial
Time Frame: Over 24 months
The proportion of participants requiring a dosage increase or the introduction of a new anti-hypertensive agent during the treatment period.
Over 24 months
Changes in the urine albumin:creatinine ratio
Time Frame: Over 24 months
The percentage change in the urine albumin:creatinine ratio for each participant
Over 24 months
Presence and category change of albuminuria
Time Frame: Over 24 months
The proportion of participants who experience albuminuria (excess albumin in the urine) during the trial period. Raw values will be recorded and albuminuria will be categorised as either A1 (<3.39mg/mmol), A2 (3.39-33.9mg/mmol), or A3 >33.9mh/mmol.
Over 24 months
Health-related quality of life
Time Frame: Over 24 months
This will measured using the EuroQual 5 Domain 5 Level (EQ-5D-5L) questionnaire
Over 24 months
ADPKD-related pain
Time Frame: Over 24 months
Mean change in the ADPKD Pain and Discomfort Scale (ADPKD-PDS) from baseline to end of study (dull kidney pain, sharp kidney pain and fullness/discomfort domain scores will be reported and analysed).
Over 24 months
Gastrointestinal symptoms
Time Frame: Over 24 months
This will be measured using the Gastrointestinal Symptom Rating Scale (GSRS). A score greater than 1.33 will signal the presence of patient-significant gastrointestinal symptomatology
Over 24 months
Presence of study-related events
Time Frame: Over 24 months
The proportion of participants who experience a specific event related to the study treatment (sub-categorised as incidence of gastrointestinal symptoms, presence of lactic acidosis, deranged liver function tests, hypoglycaemia, anaemia and vitamin B12 deficiency) expressed as a rate per 100 person years
Over 24 months
Healthcare utilisation
Time Frame: Over 24 months
Incremental cost effectiveness ratios (ICERs) will be calculated based on the incremental costs and incremental health outcomes between intervention groups
Over 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The University of Queensland

Investigators

  • Principal Investigator: Andrew Mallett, MBBS, PhD, Townsville University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 29, 2022

Primary Completion (Estimated)

December 1, 2030

Study Completion (Estimated)

December 1, 2030

Study Registration Dates

First Submitted

June 16, 2021

First Submitted That Met QC Criteria

June 16, 2021

First Posted (Actual)

June 25, 2021

Study Record Updates

Last Update Posted (Actual)

March 31, 2026

Last Update Submitted That Met QC Criteria

March 26, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AKTN16.01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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