Autosomal Dominant Polycystic Kidney DiseasePhase 3NCT04939935

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

A Phase 3 study testing Metformin XR in people with Autosomal Dominant Polycystic Kidney Disease, run by The University of Queensland at 49 sites in 3 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

Search all trials

Trial summary

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. Read more about this study

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Autosomal Dominant Polycystic Kidney Disease
What is being tested?: Metformin XR
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 1,174 participants
Where: 49 sitesin 3 countries
Study dates: 29 Nov 2022to Dec 2030
Phase: Phase 3
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

To be eligible to participate in this trial, patients must satisfy all of the following inclusion criteria:
Willing to participate and provide informed consent
Aged 18-70 years
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
eGFR equal to or greater than 38 mL/min/1.73m2 and <90 mL/min/1.73m2
And have either:

Show all 13Show fewer

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.

Who cannot join

Diabetes mellitus (as per American Diabetes Association definition), or other systemic conditions that may cause CKD independent of PKD (excluding hypertension)
Uncontrolled hypertension (Systolic BP >160 mmHg and/or diastolic BP >100 mmHg after a period of rest)
Clinically significant heart failure, including but not limited to New York Heart Association Class (NYHA) III or IV
Non-polycystic liver disease, including but not limited to:
Liver enzymes (ALT, AST or Total Bilirubin) >2 times the upper limit of normal, except when a diagnosis of Gilbert Syndrome exists and/or,
Child-Pugh classification score equal to or greater than 5

Show all 11Show fewer

Any contraindication to metformin including abnormal liver function tests or untreated Vitamin B12 deficiency
Currently taking metformin
Pregnancy or breastfeeding, or planning to get pregnant in the next three years.
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.
History of dialysis.

Trial locations and contacts

49 sites in 3 countries. Contact the study team or a site near you to ask about taking part.

Misa Matsuyama, PhD contact

+61 437 759 894

impedepkd@uq.edu.au

Pushparaj Velayudham contact

+61 438 077 278

impedepkd@uq.edu.au

Country

City, postcode or hospital

Sites recruiting now only

49 sites in 3 countries

United Kingdom31 sites, 31 recruiting

Antrim Area Hospital
Antrim, Northern Ireland, BT41 2RL
Stephanie Bolton, Dr
Stephanie Bolton, Dr
Recruiting
Ulster Hospital
Belfast, Northern Ireland, BT16 1RH
Alastair Woodman, Dr
Alastair Woodman, Dr
Recruiting
Queen Elizabeth Hospital Birmingham
Birmingham, West Midlands, B15 2GW
Yuki Heath, Dr
Yuki Heath, Dr
Not yet recruiting
Bradford Renal Unit, St Luke's Hospital
Bradford, West Yorkshire, BD5 0NA
Mohd Furqan, Dr
Mohd Furqan, Dr
Recruiting
Cardiff and Vale University Health Board
Cardiff
Mat Davies, Dr
Recruiting
St Helier Hospital
Carshalton, London, SM5 1AA
Ayesha Irtiza-Ali, Dr
Ayesha Irtiza-Ali, Dr
Not yet recruiting
Epsom and St Helier University Hospitals
Carshalton
Ayesha Irtiza-Ali, Dr
Recruiting
Doncaster Royal Infirmary
Doncaster, South Yorkshire, DN2 5LT
Mohsen El Kossi, Dr
Mohsen El Kossi, Dr
Recruiting
Royal Devon & Exeter Hospital
Exeter, Devon, EX2 5DW
Rhian Clissold, Dr
Rhian Clissold, Dr
Recruiting
Raigmore Hospital
Inverness, Inverness Shire, IV2 3UJ
Stewart Lambie, Dr
Stewart Lambie, Dr
Not yet recruiting
Leicester General Hospital
Leicester, Leicestershire, LE5 4PW
Osasuyi Iyasere, Dr
Osasuyi, Iyasere, Dr
Recruiting
Aintree University Hospital
Liverpool, Merseyside, L9 7AL
Chris Goldsmith, Dr
Chris Goldsmith, Dr
Recruiting
The Royal London Hospital
London, E1 1FR
Conor Byrne, Dr
Conor Byrne, Dr
Not yet recruiting
Royal Free Hospital
London, NW3 2QG
Daniel Gale, Dr
Daniel Gale, Dr
Not yet recruiting
King's College Hospital
London, SE5 9RS
Adam Rumjon, Dr
Adam Rumjon, Dr
Not yet recruiting
St George's University Hospital
London
Daniel Jones, Dr
Recruiting
Altnagelvin Hospital
Londonderry, Northern Ireland, BT47 6SB
Frank McCarroll, Dr
Frank McCarroll, Dr
Recruiting
Freeman Hospital
Newcastle upon Tyne, Tyne and Wear, NE7 7DN
John Sayer, Dr
John Sayer, Dr
Not yet recruiting
Daisy Hill Hospital
Newry, Northern Ireland, BT35 8DR
Neal Morgan, Dr
Neal Morgan, Dr
Not yet recruiting
Norfolk and Norwich University Hospital
Norwich, Norfolk, NR4 7UY
Matt Todd, Dr
Matt Todd, Dr
Not yet recruiting
Nottingham Renal Unit, Nottingham City Hospital
Nottingham, East Midlands, NG5 1PB
Matt Hall, Dr
Matt Hall, Dr
Not yet recruiting
Nottingham University Hospital
Nottingham
Matthew Hall, Dr
Recruiting
Oxford Kidney Unit, Churchill Hospital,
Oxford, Oxfordshire, OX3 7LE
Tom Connor, Dr
Tom Connor, Dr
Recruiting
University Hospitals Plymouth NHS Trust
Plymouth
Kris Houlberg, Dr
Recruiting
Royal Preston Hospital
Preston, Lancashire, PR2 9HT
Aimun Ahmed, Dr
Aimun Ahmed, Dr
Not yet recruiting
Salford Royal Hospital
Salford, Lancashire, M6 8HD
Grahame Wood, Dr
Aine DeBhalis, Dr
Recruiting
Sheffield Kidney Institute
Sheffield, South Yorkshire, S5 7AU
Ragada El-Damanawi, Dr
Ragada El-Damanawi, Dr
Recruiting
East & North Hertfordshire Teaching NHS Trust
Stevenage
Sivakumar Sridharan, Dr
Recruiting
Royal Stoke University Hospital
Stoke-on-Trent, Staffordshire, ST4 6QG
Dominic De Takats, Dr
Dominic De Takats, Dr
Not yet recruiting
South Tyneside and Sunderland NHS Foundation Trust
Sunderland
Shalabh Srivastava, Dr
Recruiting
York and Scarborough Teacehing Hospitals
York
Colin Jones, Dr
Recruiting

Other trials in United Kingdom

Australia13 sites

Royal Adelaide Hospital
Adelaide, South Australia, 5000
Active, not recruiting
Bundaberg Hospital
Bundaberg, Queensland, 4670
Active, not recruiting
Townsville University Hospital
Douglas, Queensland, 4814
Active, not recruiting
Renal Research
Gosford, New South Wales, 2250
Active, not recruiting
Royal Brisbane and Women's Hospital
Herston, Queensland, 4006
Active, not recruiting
Royal Melbourne Hospital
Melbourne, Victoria, 3052
Active, not recruiting
Austin Health
Melbourne, Victoria, 3084
Active, not recruiting
Monash Medical Centre
Melbourne, Victoria, 3168
Active, not recruiting
Sir Charles Gairdner Hospital
Perth, Western Australia, 6009
Active, not recruiting
Royal Prince Alfred Hospital
Sydney, New South Wales, 2050
Active, not recruiting
Royal North Shore Hospital
Sydney, New South Wales, 2065
Active, not recruiting
Westmead Hospital - Western Sydney Local Health District
Sydney, New South Wales, 2145
Active, not recruiting
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102
Active, not recruiting

Other trials in Australia

New Zealand5 sites, 5 recruiting

Te Whatu Ora - Southern
Dunedin, Otago, 9016
Ling Yap, Study Coordinator, +64 28 8514 5181, Ling.Yap@otago.ac.nz
Rob Walker, Professor
Recruiting
Te Whatu Ora - Taranaki
New Plymouth, Taranaki Region, 4310
Lynette Knuth, +64 6 753 8631, lynette.knuth@tdhb.org.nz
Mahmoud Amer, Dr
Recruiting
Ta Pae Hauora o Ruhahine o Terarua Mid Central
Palmerston North
Leila Arnold, Dr
Yuka Wrathall, Yuka.Wrathall@midcentraldhb.govt.nz
Recruiting
Te Whatu Ora - Hauora a Toi Bay of Plenty
Tauranga, Bay of Plenty, 3112
Terry Jennings, 027 507 3139, Terry.Jennings@bopdhb.govt.nz
Scott Crawford, Dr
Recruiting
Te Whatu Ora - Te Tai Tokerau
Whangārei, Northland, 0110
Rudi Koks, Study Coordinator, 021 570 098, Rudolf.Koks@northlanddhb.org.nz
Adam Mullan, Dr
Recruiting

Other trials in New Zealand

About this study

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

Read the 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.

Conditions: Autosomal Dominant Polycystic Kidney Disease
Being tested: Metformin XR, Control
Keywords: Placebo, Metformin, ADPKD
Medical subject headings: Polycystic Kidney, Autosomal Dominant

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Metformin XRDrug
Also called APO-Metformin XR (500mg)
Extended release metformin.
ControlOther
Also called Placebo
Placebo is inactive tablets that is identical to the intervention Metformin tablets.

Study groups in NCT04939935
Study group	Role	What they receive
Intervention	Experimental	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. Receives: Drug: Metformin XR
Control	Placebo comparator	Participants randomised to the control group receive placebo plus standard of care for 104 weeks. Receives: Other: Control

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Secondary outcomes (13)

Annualised slope of eGFR.
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.
Measured: Over 24 months
Composite outcome
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.
Measured: Over 24 months
Severity of change in eGFR
The proportion of participants with a reduction from baseline in their eGFR of equal to or greater than 30%.
Measured: Over 24 months
Kidney failure
The proportion of participants who experience kidney failure, defined as an eGFR <15mL/min/1.73m2.
Measured: Over 24 months
Mortality
The proportion of participants who die during the observation period, irrespective of the cause.
Measured: Over 24 months
Change in medication dosage during the trial
The proportion of participants requiring a dosage increase or the introduction of a new anti-hypertensive agent during the treatment period.
Measured: Over 24 months
Changes in the urine albumin:creatinine ratio
The percentage change in the urine albumin:creatinine ratio for each participant
Measured: Over 24 months
Presence and category change of albuminuria
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.
Measured: Over 24 months
Health-related quality of life
This will measured using the EuroQual 5 Domain 5 Level (EQ-5D-5L) questionnaire
Measured: Over 24 months
ADPKD-related pain
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).
Measured: Over 24 months
Gastrointestinal symptoms
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
Measured: Over 24 months
Presence of study-related events
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
Measured: Over 24 months
Healthcare utilisation
Incremental cost effectiveness ratios (ICERs) will be calculated based on the incremental costs and incremental health outcomes between intervention groups
Measured: Over 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

29 Nov 2022Dec 2030

First posted25 Jun 2021
Study start29 Nov 2022
Primary completionDec 2030 (estimated)
Study completionDec 2030 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (6)Papers the sponsor has linked to this study.
Other trials for Autosomal Dominant Polycystic Kidney DiseaseStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Enrolled participants will be randomised to either (1) intervention group receiving metformin extended release (XR) plus standard of care, or (2) placebo plus standard of care.
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 1,174 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04939935
Sponsor's protocol ID: AKTN16.01
Status last verified: Mar 2026
First submitted: 16 Jun 2021
Last updated: 31 Mar 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Nowak KL, Chonchol M. Cardiovascular-Kidney-Metabolic Syndrome in Autosomal Dominant Polycystic Kidney Disease. J Am Soc Nephrol. 2026 Sep 25. doi: 10.1681/ASN.0000001291. Online ahead of print. No abstract available.
PubMed 42789922
Chen CY, Hadla M, Khambati I, Kashyap S, Westerfield V, Fedeles S, Besse W, Hopp K, Harris PC, Patel V, Chini E, Salih M, Barry MA, Chebib FT. Emerging Therapies in Autosomal Dominant Polycystic Kidney Disease. Kidney360. 2026 Jul 1;7(7):1662-1676. doi: 10.34067/KID.0000001109. Epub 2025 Dec 12.
PubMed 41385299
Cortinovis M, Perico N, Remuzzi G. The Need for Novel Therapeutic Directions in Autosomal Dominant Polycystic Kidney Disease Patient Care. Clin J Am Soc Nephrol. 2025 Dec 5. doi: 10.2215/CJN.0000000975. Online ahead of print.
PubMed 41348481
Pierre KS, El-Damanawi R, Johnson DW, Hawley CM, Viecelli AK, Jha V, Green SC, Gesualdo L, Kiriwandeniya C, Velayudham P, Vergara LA, Mihala G, Matsuyama M, Brent PP, Mallett AJ; IMPEDE-PKD Global Steering Committee (see Appendix). Implementation of Metformin Therapy to Ease Decline of Kidney Function in Polycystic Kidney Disease (IMPEDE-PKD): study protocol for a phase III, multi-centre, randomized, placebo-controlled trial evaluating the long-term efficacy of metformin in slowing the rate of kidney function decline in patients with autosomal dominant polycystic kidney disease. Trials. 2025 Aug 25;26(1):302. doi: 10.1186/s13063-025-09010-6.
PubMed 40855441
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.
PubMed 39356039
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.
PubMed 38837240

Interested in taking part?

Misa Matsuyama, PhD

+61 437 759 894

impedepkd@uq.edu.au

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See sites and contacts

RecruitingObservational study
Hypertension in Children and Young People at Risk of Autosomal Dominant Polycystic Kidney Disease
Autosomal Dominant Polycystic Kidney Disease (ADPKD
Active, not recruitingObservational study
Role of ROS and cAMP-PKA Biomarkers in ADPKD
Autosomal Dominant Polycystic Kidney Disease
Not yet recruitingPhase 1
A Study to Investigate the Pharmacokinetics of JMKX003142 in Healthy Participants and Participants With Hepatic Impairment
ADPKD (Autosomal Dominant Polycystic Kidney Disease), Renal Edema
RecruitingPhase 1
Absorption, Distribution, Metabolism, and Excretion of 14C-VX-407 After a Single Oral Dose
Autosomal Dominant Polycystic Kidney Disease (ADPKD)
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders

All Autosomal Dominant Polycystic Kidney Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 31 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Implementation of Metformin theraPy to Ease Decline of Kidney Function in Polycystic Kidney Disease (IMPEDE-PKD): A Randomised Placebo-Controlled Trial
ClinicalTrials.gov ID: NCT04939935
Acronym / sponsor ID: AKTN16.01
Conditions: Autosomal Dominant Polycystic Kidney Disease
Keywords: Placebo, Metformin, ADPKD
Phase: Phase 3
Study type: Interventional
Recruitment status: Recruiting
Enrolment: 1,174 participants (estimated)
Lead sponsor: The University of QueenslandUniversity, hospital or other
Study start: 29 Nov 2022 (actual)
Primary completion: Dec 2030 (estimated)
Study completion: Dec 2030 (estimated)
First posted: 25 Jun 2021 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2
Model description: Enrolled participants will be randomised to either (1) intervention group receiving metformin extended release (XR) plus standard of care, or (2) placebo plus standard of care.

Arm	Type	Receives
Intervention	Experimental	Drug: Metformin XRParticipants 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.
Control	Placebo comparator	Other: ControlParticipants randomised to the control group receive placebo plus standard of care for 104 weeks.

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (13 listed)

To be eligible to participate in this trial, patients must satisfy all of the following inclusion criteria:
Willing to participate and provide informed consent
Aged 18-70 years
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
eGFR equal to or greater than 38 mL/min/1.73m2 and <90 mL/min/1.73m2

Key exclusion criteria (11 listed)

Diabetes mellitus (as per American Diabetes Association definition), or other systemic conditions that may cause CKD independent of PKD (excluding hypertension)
Uncontrolled hypertension (Systolic BP >160 mmHg and/or diastolic BP >100 mmHg after a period of rest)
Clinically significant heart failure, including but not limited to New York Heart Association Class (NYHA) III or IV
Non-polycystic liver disease, including but not limited to:
Any contraindication to metformin including abnormal liver function tests or untreated Vitamin B12 deficiency

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Metformin XRAlso: APO-Metformin XR (500mg)Extended release metformin.	Drug	Intervention
ControlAlso: PlaceboPlacebo is inactive tablets that is identical to the intervention Metformin tablets.	Other	Control

Primary outcome

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.

13 secondary outcomes

Annualised slope of eGFR.
Time frame: Over 24 months
Composite outcome
Time frame: Over 24 months
Severity of change in eGFR
Time frame: Over 24 months
Kidney failure
Time frame: Over 24 months
Mortality
Time frame: Over 24 months
Change in medication dosage during the trial
Time frame: Over 24 months
Changes in the urine albumin:creatinine ratio
Time frame: Over 24 months
Presence and category change of albuminuria
Time frame: Over 24 months
Health-related quality of life
Time frame: Over 24 months
ADPKD-related pain
Time frame: Over 24 months
Gastrointestinal symptoms
Time frame: Over 24 months
Presence of study-related events
Time frame: Over 24 months
Healthcare utilisation
Time frame: Over 24 months

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2026.
Derived from this study: PubMed 42789922Nowak KL, Chonchol M. Cardiovascular-Kidney-Metabolic Syndrome in Autosomal Dominant Polycystic Kidney Disease. J Am Soc Nephrol. 2026 Sep 25. doi: 10.1681/ASN.0000001291. Online ahead of print. No abstract available.
Derived from this study: PubMed 41385299Chen CY, Hadla M, Khambati I, Kashyap S, Westerfield V, Fedeles S, Besse W, Hopp K, Harris PC, Patel V, Chini E, Salih M, Barry MA, Chebib FT. Emerging Therapies in Autosomal Dominant Polycystic Kidney Disease. Kidney360. 2026 Jul 1;7(7):1662-1676. doi: 10.34067/KID.0000001109. Epub 2025 Dec 12.
Derived from this study: PubMed 41348481Cortinovis M, Perico N, Remuzzi G. The Need for Novel Therapeutic Directions in Autosomal Dominant Polycystic Kidney Disease Patient Care. Clin J Am Soc Nephrol. 2025 Dec 5. doi: 10.2215/CJN.0000000975. Online ahead of print.
Derived from this study: PubMed 40855441Pierre KS, El-Damanawi R, Johnson DW, Hawley CM, Viecelli AK, Jha V, Green SC, Gesualdo L, Kiriwandeniya C, Velayudham P, Vergara LA, Mihala G, Matsuyama M, Brent PP, Mallett AJ; IMPEDE-PKD Global Steering Committee (see Appendix). Implementation of Metformin Therapy to Ease Decline of Kidney Function in Polycystic Kidney Disease (IMPEDE-PKD): study protocol for a phase III, multi-centre, randomized, placebo-controlled trial evaluating the long-term efficacy of metformin in slowing the rate of kidney function decline in patients with autosomal dominant polycystic kidney disease. Trials. 2025 Aug 25;26(1):302. doi: 10.1186/s13063-025-09010-6.
Derived from this study: PubMed 39356039St 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.
Derived from this study: PubMed 38837240El-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.
Individual participant dataSharing planned: No

Related trials for Autosomal Dominant Polycystic Kidney Disease

RecruitingObservational study
Hypertension in Children and Young People at Risk of Autosomal Dominant Polycystic Kidney Disease
Autosomal Dominant Polycystic Kidney Disease (ADPKD
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Role of ROS and cAMP-PKA Biomarkers in ADPKD
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A Study to Investigate the Pharmacokinetics of JMKX003142 in Healthy Participants and Participants With Hepatic Impairment
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

Misa Matsuyama, PhD contact

+61 437 759 894

impedepkd@uq.edu.au

Pushparaj Velayudham contact

+61 438 077 278

impedepkd@uq.edu.au

Andrew Mallett, MBBS, PhD principal investigator

Townsville University Hospital

49 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Metformin XR in people with Autosomal Dominant Polycystic Kidney Disease, run by The University of Queensland at 49 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 31 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 49 sites in United Kingdom, Australia, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Misa Matsuyama, PhD (+61 437 759 894, impedepkd@uq.edu.au), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The change in estimated glomerular filtration rate (eGFR) (time frame: Over 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04939935, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2026.