Evaluation of Metformin and Tolvaptan in slowing disease progression of Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Metformin versus Tolvaptan in adults with Autosomal Dominant Polycystic Kidney Disease (ADPKD): a phase 3a, independent, multi-centre, 2 parallel arms randomized controlled trial - METROPOLIS

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2018-000477-77-IT

Enrollment

150

Registered

2020-11-04

Start date

2018-11-08

Completion date

Unknown

Last updated

2025-01-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Autosomal Dominant Polycystic Kidney Disease MedDRA version: 20.0 Level: LLT Classification code 10036046 Term: Polycystic kidney, autosomal dominant System Organ Class: 100000004850

Interventions

Trade Name: ZUGLIMET - 500 MG COMPRESSE RIVESTITE CON FILM 30 COMPRESSE IN BLISTER PVC/AL Product Name: METFORMINA Product Code: [METFORMINA] Pharmaceutical Form: Coated tablet INN or Proposed INN: ME

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1) Men and women aged between 18 and 50 years 2) eGFR (CKD-epi) = 45 ml/min/1,73 m2 3) Genetic Diagnosis of Type I ADPKD truncating mutation 4) Signed and dated informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 150 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: 1) Women of childbearing potential (WOCBP) who do not agree to practice 2 different methods of birth control or remain abstinent during the trial and for 30 days after the last dose of IMP. If employing birth control, 2 of the following precautions must be used: vasectomy of partner, tubal ligation, vaginal diaphragm, intrauterine device, birth control implant, condom, or sponge with spermicide. Non-childbearing potential in women is defined as female subjects who are surgically sterile (ie, have undergone bilateral oophorectomy or hysterectomy) or female subjects who have been postmenopausal for at least 12 consecutive months. 2) Women who are breast-feeding and/or who have a positive pregnancy test result prior to receiving investigational medical product (IMP). 3) Treatment with acarbose, guar gum, cimetidin, phenprocoumon, oral anticoagulants, thrombolytic drugs, diuretics, ranolazin, cephalexin. 4) Evidence of active systemic or localized major infection at the time of screening. 5) Hepatic impairment or liver function abnormalities other than that expected for ADPKD with typical cystic liver disease during the screening period as defined by: o AST O ALT >8x UNL o AST O ALT >5x UNL >2 WEEKS o AST O ALT >3x UNL E BT >2x UNL OR INR >1,5 o AST O ALT >3x UNL E SIGNS AND SYMPTOMS OF LIVER DAMAGE (fatigue, anorexy, nausea, vomiting, right hypocondrium pain, fever, jaundice, skin rash, itching) 6) Acute or chronic disease causing tissue hypoxia (e.g.: myocardial failure, severe arythmias, myocardial infarction, respiratory failure, liver failure, alcohol acute intoxication, alcoholism, dehydration). 7) Previously diagnosed diabetes already in treatment with other hypoglycemic drugs. 8) Ongoing breast feeding. 9) Use of any other investigational drug or treatment up to 4 weeks before enrollment and during the treatment phase. 10) Known hypersensitivity to metformin and its derivatives. 11) Psychiatric disorders and any condition that might prevent full comprehension of the purposes and risks of the study. 12) Malignancies within three years before enrolment in the study. 13) HIV, HBV, HCV infection. 14) Urinary tract obstruction.

Design outcomes

Primary

Measure	Time frame
Main Objective: Primary objective of the study is to define if a two years course of 1500 mg a day of metformin is equivalent or not inferior to tolvaptan in reducing eGFR decline in patients affected by ADPKD. ;Secondary Objective: Secondary objectives are to define if Metformin tratment for ADPKD is safe and effective in reducing kidney volume enlargement and in reducing symptoms related to this pathology.;Primary end point(s): Primary outcome of the study is to evaluate the treatments difference (between Metformin and Tolvaptan) in annualized slope of eGFR (CKD-epi) for individual subjects will be calculated using an appropriate baseline and post-randomization assessment.;Timepoint(s) of evaluation of this end point: Throughout study up to the Follow up period (3 week post treatment end).	—

Measure

Time frame

Main Objective: Primary objective of the study is to define if a two years course of 1500 mg a day of metformin is equivalent or not inferior to tolvaptan in reducing eGFR decline in patients affected by ADPKD. ;Secondary Objective: Secondary objectives are to define if Metformin tratment for ADPKD is safe and effective in reducing kidney volume enlargement and in reducing symptoms related to this pathology.;Primary end point(s): Primary outcome of the study is to evaluate the treatments difference (between Metformin and Tolvaptan) in annualized slope of eGFR (CKD-epi) for individual subjects will be calculated using an appropriate baseline and post-randomization assessment.;Timepoint(s) of evaluation of this end point: Throughout study up to the Follow up period (3 week post treatment end).

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Secondary

Measure	Time frame
Secondary end point(s): The key secondary endpoint is the percent change from baseline in htTKV as measured by CT-scan at 12 and 24 months.;Timepoint(s) of evaluation of this end point: At the end of the treatment period	—

Countries

Italy

Contacts

Public ContactU.O Nefrologia, Dialisi e Trapianto

Azienda ospedaliero universitaria policlinico di Bari

trialnefrobari@gmail.com+390805592778

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026