Metformin vs Tolvaptan for Treatment of Autosomal Dominant Polycystic Kidney Disease (METROPOLIS)
ADPKD
About this trial
This is an interventional treatment trial for ADPKD
Eligibility Criteria
Inclusion Criteria:
- Men and women aged between 18 and 50 years
- eGFR (CKD-EPI) ≥ 45 ml/min/1,73 m2
- Genetic Diagnosis of Type I ADPKD truncating mutation
- Signed and dated informed consent
Exclusion Criteria:
- 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.
- Women who are breast-feeding and/or who have a positive pregnancy test result prior to receiving investigational medical product (IMP).
- Treatment with acarbose, guar gum, cimetidin, phenprocoumon, oral anticoagulants, thrombolytic drugs, diuretics, ranolazin, cephalexin.
- Evidence of active systemic or localized major infection at the time of screening.
Hepatic impairment or liver function abnormalities other than that expected for ADPKD with typical cystic liver disease during the screening period as defined by:
- AST O ALT >8x UNL
- AST O ALT >5x UNL >2 WEEKS
- AST O ALT >3x UNL E BT >2x UNL OR INR >1,5
- AST O ALT >3x UNL E SIGNS AND SYMPTOMS OF LIVER DAMAGE (fatigue, anorexy, nausea, vomiting, right hypocondrium pain, fever, jaundice, skin rash, itching)
- Acute or chronic disease causing tissue hypoxia (e.g.: myocardial failure, severe arythmias, myocardial infarction, respiratory failure, liver failure, alcohol acute intoxication, alcoholism, dehydration).
- Previously diagnosed diabetes already in treatment with other hypoglycemic drugs.
- Ongoing breast feeding.
- Use of any other investigational drug or treatment up to 4 weeks before enrollment and during the treatment phase.
- Known hypersensitivity to metformin and its derivatives.
- Psychiatric disorders and any condition that might prevent full comprehension of the purposes and risks of the study.
- Malignancies within three years before enrolment in the study.
- HIV, HBV, HCV infection.
- Urinary tract obstruction.
Sites / Locations
- AOUC "Policlinico"
- AOUConsorziale Policlinico Di Bari
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Metformin
Tolvaptan
Patients will take metformin starting from 500 mg a day. They will up-titrate every week, if tolerating IMP, adding one 500 mg dose 8 hours after the former, till reaching 500 mg thrice a day. The minimum tolerated dose requested in order to be admitted to the study is 500 mg twice a day. Those reaching eGFR<45 ml/min will reduce the dose by one third. Those reaching eGFR<30 will drop out the study.
Patient will start Tolvaptan in a split dose regimen 45 mg as first dose, followed by 15 mg 8 hours later. Those tolerating this dose will uptitrate to 60/30 mg and then to 90/30 mg a day. Those not tolerating 45/15 mg a day will drop out.