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| ID | Type | Description | Link |
|---|---|---|---|
| R21DK107969-01A1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metformin | Drug | Monitoring of safety and tolerability |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 12 months |
| Change in Kidney Function |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Godela M Brosnahan, MD | University of Colorado, Denver | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Colorado Denver, Anschutz Medical Campus | Aurora | Colorado | 80045 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21262823 | Background | 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. | |
| 23825068 | Background | Satriano 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. |
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5 participants screen failed or dropped out prior to randomization
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | Posted | Number | percentage of participants | 12 months |
|
12 Months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Infection | Infections and infestations | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Godela Brosnahan, MD | University of Colorado Denver | Anschutz | 3037241111 | clinicalresearchsupportcenter@ucdenver.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 20, 2019 | Aug 10, 2021 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | May 8, 2018 | Aug 10, 2021 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D016891 | Polycystic Kidney, Autosomal Dominant |
| ID | Term |
|---|---|
| D007690 | Polycystic Kidney Diseases |
| D052177 | Kidney Diseases, Cystic |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
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| ID | Term |
|---|---|
| D008687 | Metformin |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
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| Placebo | Drug | Monitoring of safety and tolerability |
|
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. |
| 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 | 12 months |
| 23592561 | Background | Hung 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. |
| 39356039 | Derived | St 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. |
| 38837240 | Derived | El-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. |
| 34391872 | Derived | Brosnahan 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. |
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 |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| 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. | 2 participants (1 from each group) were not analyzed due to insufficient image quality for accurate analysis. | Posted | Mean | Standard Error | percent change | 12 months |
|
|
|
| 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. | Posted | Mean | Standard Error | mL/min/1.73 m^2 | 12 months |
|
|
|
| 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 | Posted | Count of Participants | Participants | 12 months |
|
|
|
| 0 |
| 26 |
| 2 |
| 26 |
| 26 |
| 26 |
| EG001 | 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 | 0 | 25 | 0 | 25 | 25 | 25 |
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Non-systematic Assessment |
|
| Acid Reflux | Gastrointestinal disorders | Non-systematic Assessment |
|
| Light-headedness | General disorders | Non-systematic Assessment |
|
| Weakness | General disorders | Non-systematic Assessment |
|
| Viral Illness | Infections and infestations | Non-systematic Assessment |
|
| sinus infection | Infections and infestations | Non-systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | Non-systematic Assessment |
|
| Abdominal cramping/pain | Gastrointestinal disorders | Non-systematic Assessment |
|
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| D052776 |
| Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D000015 | Abnormalities, Multiple |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D000072661 | Ciliopathies |
| D030342 | Genetic Diseases, Inborn |