Metformin for Romanian patients with autosomal dominant polycystic kidney disease
| ISRCTN | ISRCTN93749377 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN93749377 |
| Secondary identifying numbers | 39436 |
- Submission date
- 16/02/2019
- Registration date
- 25/02/2019
- Last edited
- 25/07/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Genetic Diseases
Plain English summary of protocol
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
Contact information
Scientific
Fundeni Clinical Institute
Fundeni Street no. 258
Bucharest
022328
Romania
| Phone | +40213119190 |
|---|---|
| gener.ismail@umfcd.ro |
Study information
| Study design | Prospective, Interventional, Single-arm, Single-center study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format. Please use contact details to request PIS. |
| 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 |
| Study acronym | METROP |
| Study objectives | 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(s) | 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 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | 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 study start date | 01/11/2015 |
| Completion date | 31/12/2018 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 34 |
| Total final enrolment | 34 |
| Key inclusion criteria | 1. Age ≥ 18 years 2. Diagnosis of ADPKD based on unified ultrasonographic Pei-Ravine criteria 3. CKD G1-G5 not on dialysis. |
| Key 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 |
| Date of first enrolment | 01/04/2016 |
| Date of final enrolment | 31/12/2016 |
Locations
Countries of recruitment
- Romania
Study participating centre
District no. 2
Bucharest
022328
Romania
Sponsor information
Not defined
Fundeni Street no. 258
Bucuresti
022238
Romania
| Phone | +40722792429 |
|---|---|
| gener732000@yahoo.com | |
"ROR" |
https://ror.org/05w6fx554 |
Funders
Funder type
Hospital/treatment centre
No information available
Results and Publications
| Intention to publish date | 31/03/2019 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a high-impact open-access, peer-reviewed journal. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 23/07/2019 | 25/07/2019 | Yes | No |
Editorial Notes
25/07/2019: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.
