Polycystic Kidney, Autosomal DominantPhase 2NCT02903511
Feasibility Study of Metformin Therapy in ADPKD
A Phase 2 study testing Metformin in people with Polycystic Kidney, Autosomal Dominant, run by University of Colorado, Denver at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 to 60 years
- Conditions the study is for
- Polycystic Kidney, Autosomal Dominant
- What is being tested?
- Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 56 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2016to 17 Aug 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- Diabetes mellitus,
- Active infection,
- Congestive heart failure,
- Liver disease,
- Alcohol or substance dependence,
- Cigarette smoking within the last 12 months;
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Denver, Anschutz Medical Campus
Aurora, Colorado, 80045
About this study
Official title: Feasibility Study of Metformin Therapy in Autosomal Dominant Polycystic Kidney Disease.
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.
Read the 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.
- Conditions
- Polycystic Kidney, Autosomal Dominant
- Being tested
- Metformin, Placebo
- Keywords
- Metformin, total kidney volume, glomerular filtration rate
- Medical subject headings
- Polycystic Kidney, Autosomal Dominant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Also called Glucophage, Fortamet, Glumetza
Monitoring of safety and tolerability
PlaceboDrug
Monitoring of safety and tolerability
| Study group | Role | What they receive |
|---|---|---|
| Metformin | Experimental | 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. Receives: Drug: Metformin |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 12 months
Secondary outcomes (3)
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.
Measured: 12 months
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.
Measured: 12 months
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
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2016 (estimated)
- Study startNov 2016
- Primary completion17 Aug 2020
- Study completion17 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Polycystic Kidney, Autosomal DominantStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Godela M Brosnahan, MD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02903511
- Sponsor's protocol ID
- 16-0802
- Other IDs
- R21DK107969-01A1
- Status last verified
- Aug 2021
- First submitted
- 13 Sep 2016
- Last updated
- 5 Sep 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Takiar V, Nishio S, Seo-Mayer P, King JD Jr, Li H, Zhang L, Karihaloo A, Hallows KR, Somlo S, Caplan MJ. Activating AMP-activated protein kinase (AMPK) slows renal cystogenesis. Proc Natl Acad Sci U S A. 2011 Feb 8;108(6):2462-7. doi: 10.1073/pnas.1011498108. Epub 2011 Jan 24.
PubMed 21262823Satriano J, Sharma K, Blantz RC, Deng A. Induction of AMPK activity corrects early pathophysiological alterations in the subtotal nephrectomy model of chronic kidney disease. Am J Physiol Renal Physiol. 2013 Sep 1;305(5):F727-33. doi: 10.1152/ajprenal.00293.2013. Epub 2013 Jul 3.
PubMed 23825068Hung AM, Roumie CL, Greevy RA, Liu X, Grijalva CG, Murff HJ, Griffin MR. Kidney function decline in metformin versus sulfonylurea initiators: assessment of time-dependent contribution of weight, blood pressure, and glycemic control. Pharmacoepidemiol Drug Saf. 2013 Jun;22(6):623-31. doi: 10.1002/pds.3432.
PubMed 23592561St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.
PubMed 39356039El-Damanawi R, Stanley IK, Staatz C, Pascoe EM, Craig JC, Johnson DW, Mallett AJ, Hawley CM, Milanzi E, Hiemstra TF, Viecelli AK. Metformin for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2024 Jun 4;6(6):CD013414. doi: 10.1002/14651858.CD013414.pub2.
PubMed 38837240Brosnahan GM, Wang W, Gitomer B, Struemph T, George D, You Z, Nowak KL, Klawitter J, Chonchol MB. Metformin Therapy in Autosomal Dominant Polycystic Kidney Disease: A Feasibility Study. Am J Kidney Dis. 2022 Apr;79(4):518-526. doi: 10.1053/j.ajkd.2021.06.026. Epub 2021 Aug 12.
PubMed 34391872
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Feasibility Study of Metformin Therapy in Autosomal Dominant Polycystic Kidney Disease.
- ClinicalTrials.gov ID
- NCT02903511
- Acronym / sponsor ID
- 16-0802
- Conditions
- Polycystic Kidney, Autosomal Dominant
- Keywords
- Metformin, total kidney volume, glomerular filtration rate
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Nov 2016
- Primary completion
- 17 Aug 2020 (actual)
- Study completion
- 17 Aug 2020 (actual)
- First posted
- 16 Sep 2016 (estimated)
- Results
- Posted 5 Sep 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metformin | Experimental | Drug: MetforminParticipants 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. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants 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. |
Who may qualify
- Ages
- 30 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (10 listed)
- Diabetes mellitus,
- Active infection,
- Congestive heart failure,
- Liver disease,
- Alcohol or substance dependence,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetforminAlso: Glucophage, Fortamet, GlumetzaMonitoring of safety and tolerability | Drug | Metformin |
| PlaceboMonitoring of safety and tolerability | Drug | Placebo |
Primary outcome
Safety and Tolerability of Metformin
Time frame: 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
3 secondary outcomes
Change in Total Kidney Volume
Time frame: 12 months
Change in Kidney Function
Time frame: 12 months
Rate of Serious Adverse Events (SAE)
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21262823Takiar V, Nishio S, Seo-Mayer P, King JD Jr, Li H, Zhang L, Karihaloo A, Hallows KR, Somlo S, Caplan MJ. Activating AMP-activated protein kinase (AMPK) slows renal cystogenesis. Proc Natl Acad Sci U S A. 2011 Feb 8;108(6):2462-7. doi: 10.1073/pnas.1011498108. Epub 2011 Jan 24.
- Background: PubMed 23825068Satriano J, Sharma K, Blantz RC, Deng A. Induction of AMPK activity corrects early pathophysiological alterations in the subtotal nephrectomy model of chronic kidney disease. Am J Physiol Renal Physiol. 2013 Sep 1;305(5):F727-33. doi: 10.1152/ajprenal.00293.2013. Epub 2013 Jul 3.
- Background: PubMed 23592561Hung AM, Roumie CL, Greevy RA, Liu X, Grijalva CG, Murff HJ, Griffin MR. Kidney function decline in metformin versus sulfonylurea initiators: assessment of time-dependent contribution of weight, blood pressure, and glycemic control. Pharmacoepidemiol Drug Saf. 2013 Jun;22(6):623-31. doi: 10.1002/pds.3432.
- Derived from this study: PubMed 39356039St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.
- Derived from this study: PubMed 38837240El-Damanawi R, Stanley IK, Staatz C, Pascoe EM, Craig JC, Johnson DW, Mallett AJ, Hawley CM, Milanzi E, Hiemstra TF, Viecelli AK. Metformin for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2024 Jun 4;6(6):CD013414. doi: 10.1002/14651858.CD013414.pub2.
- Derived from this study: PubMed 34391872Brosnahan GM, Wang W, Gitomer B, Struemph T, George D, You Z, Nowak KL, Klawitter J, Chonchol MB. Metformin Therapy in Autosomal Dominant Polycystic Kidney Disease: A Feasibility Study. Am J Kidney Dis. 2022 Apr;79(4):518-526. doi: 10.1053/j.ajkd.2021.06.026. Epub 2021 Aug 12.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Godela M Brosnahan, MD principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Metformin in people with Polycystic Kidney, Autosomal Dominant, run by University of Colorado, Denver at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and Tolerability of Metformin (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02903511, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2021.