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

PHASE3RECRUITING

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.

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Study details:

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.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

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

Exclusion criteria

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

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

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Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2022-11-29

Primary completion: 2026-12-01

Study completion finish: 2027-05-01

Study type

TREATMENT

Phase

PHASE3

Trial ID

NCT04939935

Intervention or treatment

DRUG: Metformin XR

OTHER: Control

Conditions

• Autosomal Dominant Polycystic Kidney Disease

Image related to Autosomal Dominant Polycystic Kidney Disease

Condition: Autosomal Dominant Polycystic Kidney Disease
DRUG: Metformin XR and other drugs
Sydney, New South Wales, Australia and more
Sponsor: The University of Queensland

You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

Are you running this trial? If you're a clinic or sponsor, you can claim this study. Claim or learn more.

Find a site

Closest Location:

Royal Prince Alfred Hospital

Research sites nearby

Select from list below to view details:

Royal Prince Alfred Hospital
Sydney, New South Wales, Australia
Bundaberg Hospital
Bundaberg, Queensland, Australia
Royal Brisbane and Women's Hospital
Herston, Queensland, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia

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?

Participant Group/Arm	Intervention/Treatment
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.
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.

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
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.	Over 24 months

Secondary outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
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.	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.	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%.	Over 24 months
Kidney failure	The proportion of participants who experience kidney failure, defined as an eGFR \<15mL/min/1.73m2.	Over 24 months
Mortality	The proportion of participants who die during the observation period, irrespective of the cause.	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.	Over 24 months
Changes in the urine albumin:creatinine ratio	The percentage change in the urine albumin:creatinine ratio for each participant	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.	Over 24 months
Health-related quality of life	This will measured using the EuroQual 5 Domain 5 Level (EQ-5D-5L) questionnaire	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).	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	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	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	Over 24 months

Frequently Asked Questions

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You may be eligible to participate in this trial based on your search.Apply for study

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References

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