Plain English Summary
Background and study aims
Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disease that affects the kidneys. In Europe, there are approximately 3 cases per 10,000 people. It is characterized by bilateral renal cysts (fluid filled sacs) that grow in number and size over time and produce loss of kidney function. Metformin is a drug that has been used to treat high blood sugar levels in patients with diabetes mellitus for many years, but research has shown that it could also slow the growth of renal cysts. Also, it has been demonstrated that Metformin could produce weight loss in overweight and obese patients. Apart from the direct effect on renal cysts growth, Metformin could have an additional beneficial effect in controlling kidney damage by producing weight loss in ADPKD patients. Based on these considerations, our aim was to evaluate how Metformin is tolerated in ADPKD patients and if these patients could have benefits on kidney function and weight loss.
Who can participate?
Adult patients with diagnosis of ADPKD with any stage CKD stages between G1-G5 not on dialysis.
What does the study involve?
Patients received an initial dose of Metformin of 500 mg/day within the first month, that was increased to 1000 mg/day (500 mg twice daily), depending on tolerance and adverse events. The dose of Metformin in patients with CKD stage G5 was limited to 500 mg/day throughout the duration of the study. The study follow-up period was of 24 months. In the first year, visits were established at 1, 4 and 12 months, and after this period, at 18 and 24 months. At baseline, data regarding personal medical history, family history of ADPKD, demographic, smoking status and antihypertensive drugs were collected. Also, at baseline and at each study visit, patients were questioned about drug tolerability, underwent physical examination, including BMI assessment and laboratory tests were performed, including: glycemic and lipid profiles, liver tests, renal function tests, lactic acid levels, complete blood count and urinary tests. After 24 months of treatment tolerability, safety and efficacy outcomes were analyzed.
What are the possible benefits and risks of participating?
All participants will have the opportunity to receive a regular general evaluation and possible benefits regarding kidney function and weigh loss on those overweight or obese. Possible side effects of the treatment with Metformin include nausea, vomiting, diarrhea, abdominal pain, bloating, dizziness, skin rash or, more rarely, issues regarding decrease in blood glucose level or increase of lactate level.
Where is the study run from?
Fundeni Clinical Institute, Department of Nephrology, Bucharest, Romania, Fundeni Street No. 258, District no. 2.
When is the study starting and how long is it expected to run for?
Between April 2016 and December 2018
Who is funding the study?
Fundeni Clinical Institute
Who is the main contact?
Dr. Gener Ismail, gener732000@yahoo.com
Trial website
Contact information
Type
Scientific
Primary contact
Dr Gener Ismail
ORCID ID
Contact details
Fundeni Clinical Institute
Fundeni Street no. 258
Bucharest
022328
Romania
+40213119190
gener.ismail@umfcd.ro
Additional identifiers
EudraCT number
Nil known
ClinicalTrials.gov number
Nil known
Protocol/serial number
39436
Study information
Scientific title
A preliminary, single-center, prospective, interventional, single-arm study investigating the safety, tolerability and efficacy of Metformin in Romanian adult patients with autosomal dominant polycystic kidney disease
Acronym
METROP
Study hypothesis
Metformin has shown promising results regarding cystogenesis inhibition in autosomal dominant polycystic kidney disease (ADPKD) in preclinical studies and also it was shown that it can lead to weight loss in overweight and obese patients. Apart from the direct effect on cystogenesis, Metformin could have a beneficial additional effect in controlling the decline of renal function by producing a decrease in body mass index.
Ethics approval
Approved 28/11/2016, local ethical board of Fundeni Clinical Institute (Fundeni Street no. 258, 022328, Bucharest, Romania; +40 724545131; secretariat@icfundeni.ro), ref: 39436
Study design
Prospective, Interventional, Single-arm, Single-center study
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format. Please use contact details to request PIS.
Condition
Autosomal Dominant Polycystic Kidney Disease
Intervention
Patients received an initial dose of Metformin of 500 mg/day within the first month, that was increased to 1000 mg/day (500 mg twice daily), depending on tolerance and adverse events. Patients with CKD stage G5 received only 500 mg/day throughout the duration of the study. The study follow-up period was of 24 months.
Intervention type
Drug
Phase
Not Specified
Drug names
Metformin
Primary outcome measure
Assessment of the tolerability and safety of Metformin in patients with ADPKD, which included an evaluation of the number and type of gastrointestinal and non-gastrointestinal symptoms and the evaluation of hypoglycemia, lactic acidosis, death and other adverse events, measured at baseline, 1 month, 4 months, 12 months, 18 months and 24 months using patient interviews, physical exam and laboratory tests (glycemic profile, lactate levels, complete blood count, renal ultrasound).
Secondary outcome measures
1. Change in kidney function from baseline is evaluated based on serum creatinine, estimated with CKD-EPI formula and expressed as eGFR after 1, 4, 12, and 24 months of treatment
2. The number/ percentage of patients that needed renal replacement therapy is measured using patient interviews, physical exam, laboratory tests (electrolytes, acid-base, creatinine, urea) at every visit or whenever is necessary
3. Change in body mass index from baseline is evaluated based on anthropometric measurements of weight and hight after 1, 4, 12, and 24 months of treatment
Overall trial start date
01/11/2015
Overall trial end date
31/12/2018
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Age ≥ 18 years
2. Diagnosis of ADPKD based on unified ultrasonographic Pei-Ravine criteria
3. CKD G1-G5 not on dialysis.
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
34
Total final enrolment
34
Participant exclusion criteria
1. Diabetes mellitus
2. Active infections
3. Pregnant or breastfeeding patients,
4. Known contraindication or allergy to Metformin
5. Receiving renal replacement therapy
Recruitment start date
01/04/2016
Recruitment end date
31/12/2016
Locations
Countries of recruitment
Romania
Trial participating centre
Fundeni Clinical institute, Department of Nephrology
Fundeni Street no. 258
District no. 2
Bucharest
022328
Romania
Sponsor information
Organisation
Fundeni Clinical institute
Sponsor details
Fundeni Street no. 258
Bucuresti
022238
Romania
+40722792429
gener732000@yahoo.com
Sponsor type
Not defined
Website
Funders
Funder type
Hospital/treatment centre
Funder name
Fundeni Clinical Institute
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Planned publication in a high-impact open-access, peer-reviewed journal.
IPD sharing statement:
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request
Intention to publish date
31/03/2019
Participant level data
Available on request
Basic results (scientific)
Publication list
2019 results in: https://www.ncbi.nlm.nih.gov/pubmed/31337351 (added 25/07/2019)