Polycystic Kidney, Autosomal Dominant
Conditions
Keywords
Metformin, total kidney volume, glomerular filtration rate
Brief summary
This study is being done to determine if treatment with metformin, a drug widely used for the treatment of diabetes type 2, is safe and well tolerated by individuals with Autosomal Dominant Polycystic Kidney Disease (ADPKD) who are not diabetic and who have slightly decreased kidney function. The study will also evaluate the effects of metformin on kidney growth and kidney function.
Detailed description
Patients with ADPKD are still in need for a well-tolerated treatment that can be used long-term to prevent cyst growth and kidney function decline. Metformin has a long track record of a low risk-to-benefit profile in patients with diabetes or at risk for diabetes. Metformin inhibits two key processes responsible for the growth of polycystic kidneys, i.e. fluid secretion and cell proliferation, as shown in cell cultures and animal models of ADPKD. Experiments in animal models of chronic kidney disease demonstrate that metformin administration prevents kidney fibrosis and preserves kidney function. Diabetic patients who are treated with metformin appear to develop less kidney failure and live longer than patients who are treated with other anti-diabetic medications. Therefore this drug is promising for people with ADPKD, with the potential to slow cyst enlargement and preserve kidney function.
Interventions
DRUGMetformin
Monitoring of safety and tolerability
DRUGPlacebo
Monitoring of safety and tolerability
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Autosomal Dominant Polycystic Kidney Disease and * An estimated glomerular filtration (GFR) rate of 50-80 ml/min/1.73 m2; * Subject is able to sign an Informed Consent
Exclusion criteria
* Diabetes mellitus, * Active infection, * Congestive heart failure, * Liver disease, * Alcohol or substance dependence, * Cigarette smoking within the last 12 months; * Females who are pregnant or breast feeding, or * Are unwilling to use contraception; * Are unable to undergo magnetic resonance imaging, or * Have a contraindication to the use of metformin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of Metformin | 12 months | Percentage of participants who at the end of 12 months are still prescribed the full randomized dose of metformin or placebo, and the percentage of participants who are prescribed at least 50% of the randomized dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Total Kidney Volume | 12 months | Total kidney volume will be measured by MRI (magnetic resonance imaging) at baseline and at 12 months. Percentage change from baseline in height-adjusted total kidney volume is reported. |
| Change in Kidney Function | 12 months | Estimated glomerular filtration rate (eGFR) will be calculated from serum creatinine measurements at baseline and after 3, 6, 9 and 12 months. Change from baseline at 12 months is reported. |
| Rate of Serious Adverse Events (SAE) | 12 months | Serious adverse events occurring from the time of signing informed consent until the end of the study will be monitored in both treatment arms |
Countries
United States
Participant flow
Pre-assignment details
5 participants screen failed or dropped out prior to randomization
Participants by arm
| Arm | Count |
|---|---|
| Metformin Participants will receive metformin 500 mg tablets, starting with 1 tab twice a day. The dose will be increased by 500 mg every 2 weeks up to 1000 mg by mouth twice a day, as tolerated, for 12 months.
Metformin: Monitoring of safety and tolerability | 26 |
| Placebo Participants will receive placebo 500 mg tablets, starting with 1 tab twice a day. The dose will be increased by 500 mg every 2 weeks up to 1000 mg by mouth twice a day, as tolerated, for 12 months.
Placebo: Monitoring of safety and tolerability | 25 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Metformin | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 48 years STANDARD_DEVIATION 8 | 48 years STANDARD_DEVIATION 8 | 48 years STANDARD_DEVIATION 7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants | 50 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 26 Participants | 51 Participants | 25 Participants |
| Region of Enrollment United States | 26 participants | 51 participants | 25 participants |
| Sex: Female, Male Female | 15 Participants | 32 Participants | 17 Participants |
| Sex: Female, Male Male | 11 Participants | 19 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 25 |
| other Total, other adverse events | 26 / 26 | 25 / 25 |
| serious Total, serious adverse events | 2 / 26 | 0 / 25 |
Outcome results
Primary
Safety and Tolerability of Metformin
Percentage of participants who at the end of 12 months are still prescribed the full randomized dose of metformin or placebo, and the percentage of participants who are prescribed at least 50% of the randomized dose
Time frame: 12 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Metformin | Safety and Tolerability of Metformin | Full Dose | 50 percentage of participants |
| Metformin | Safety and Tolerability of Metformin | 50% Dose | 82 percentage of participants |
| Placebo | Safety and Tolerability of Metformin | Full Dose | 100 percentage of participants |
| Placebo | Safety and Tolerability of Metformin | 50% Dose | 100 percentage of participants |
Secondary
Change in Kidney Function
Estimated glomerular filtration rate (eGFR) will be calculated from serum creatinine measurements at baseline and after 3, 6, 9 and 12 months. Change from baseline at 12 months is reported.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin | Change in Kidney Function | -0.41 mL/min/1.73 m^2 | Standard Error 1.81 |
| Placebo | Change in Kidney Function | -3.35 mL/min/1.73 m^2 | Standard Error 1.7 |
Secondary
Change in Total Kidney Volume
Total kidney volume will be measured by MRI (magnetic resonance imaging) at baseline and at 12 months. Percentage change from baseline in height-adjusted total kidney volume is reported.
Time frame: 12 months
Population: 2 participants (1 from each group) were not analyzed due to insufficient image quality for accurate analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin | Change in Total Kidney Volume | 3.45 percent change | Standard Error 1.3 |
| Placebo | Change in Total Kidney Volume | 3.15 percent change | Standard Error 1.61 |
Secondary
Rate of Serious Adverse Events (SAE)
Serious adverse events occurring from the time of signing informed consent until the end of the study will be monitored in both treatment arms
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Metformin | Rate of Serious Adverse Events (SAE) | 2 Participants |
| Placebo | Rate of Serious Adverse Events (SAE) | 0 Participants |