- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02656017
Metformin as a Novel Therapy for Autosomal Dominant Polycystic Kidney Disease (TAME)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Maryland
-
Baltimore, Maryland, United States, 21201
- University of Maryland Medical Center
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02111
- Tufts Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Subject has Autosomal Dominant Polycystic Kidney Disease; Subject is fluent in English
Exclusion Criteria:
Subject is not on active military duty; Subject is not currently participating in another clinical trial; Subject's current GFR is not <50 cc/min/1.73m2; Subject does not have diabetes; Subject does not have a systemic disease other than hypertension and PKD; Subject does not have a solitary kidney; Subject does not have an allergy or intolerance to metformin; Subject is not pregnant or lactating or intending to become pregnant within the next three years; Subject does not have an unstable or unclipped cerebral aneurysm; Subject does not have active coronary artery disease; Subject does not have an MRI incompatible device/implant; Subject does not have severe claustrophobia; Subject has not had any solid organ transplant; Subject does not have a Vitamin B12 deficiency; Subject does not currently take any medications that interact with metformin, such as nifedipine, furosemide, cationic drugs (amiloride, ranitidine, triamterene digoxin, procainamide, quinidine, vancomycin, trimethoprim); Subject does not currently take nor has taken (within 2 weeks) the drug tolvaptan (Jynarque or Samsca)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Metformin
Participants will be started on 500 mg of metformin once daily, with the following scheduled dose titrations:
|
Monitoring of tolerability and symptoms.
Other Names:
|
Placebo Comparator: Placebo
Participants will be started on 500 mg of placebo once daily, with the following scheduled dose titrations:
|
Monitoring of tolerability and symptoms.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in the Gastrointestinal Symptoms Rating Scale (GSRS) to 24 Months
Time Frame: Baseline, 2 weeks, 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 months
|
GSRS is a widely used, validated 15-item questionnaire used to assess GI symptom burden (minimum, maximum: 1, 7, where higher mean score is worse outcome). Mean change to 24 months, estimated with a repeated measures analysis (baseline, 2 weeks, 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 months) using a linear mixed model. |
Baseline, 2 weeks, 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 months
|
Drug Tolerability
Time Frame: Baseline, 2 weeks, 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 months
|
Tolerability was based on the first visit a participant responded no to the following question "Can you tolerate this dose of study drug the rest of your life?", which was asked at baseline, 2 weeks, 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 months.
|
Baseline, 2 weeks, 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 months
|
Rate of Serious Adverse Events (SAE)
Time Frame: 26 months
|
Serious adverse events (SAE) occurring from the time a participant signs the informed consent (at the screening visit) until the end of the study, meeting 1 or more of the criteria of: 1) Resulting in death, 2) Non-elective hospitalization, 3) Life threatening (if patient continued on study drug would result in death), 4) Harming or disabling persistently or permanently , 5) Exceeding the nature, severity or frequency of risk described in the protocol or 6) Resulting in congenital anomaly.
|
26 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Quality of Life Physical Component
Time Frame: Baseline, 1 month, 3 months and every 3 months thereafter to 24 months
|
Short Form-36 Quality of Life Physical Component Summary (SF-36 PCS) ranges from 0 (worst possible outcome) to 100 (best possible outcome). Mean change to 24 months, estimated with a repeated measures analysis (baseline, 1 month, 3 months and every 3 months thereafter to 24 months) using a linear mixed model. |
Baseline, 1 month, 3 months and every 3 months thereafter to 24 months
|
Quality of Life Mental Component
Time Frame: Baseline, 1 month, 3 months and every 3 months thereafter to 24 months
|
Short Form-36 Quality of Life Mental Component Summary (SF-36 MCS) ranges from 0 (worst possible outcome) to 100 (best possible outcome). Mean change to 24 months, estimated with a repeated measures analysis (baseline, 1 month, 3 months and every 3 months thereafter to 24 months) using a linear mixed model. |
Baseline, 1 month, 3 months and every 3 months thereafter to 24 months
|
Back Pain Frequency Over the Past 3 Months Since Last Visit
Time Frame: Baseline, 1 month, 3 months and every 3 months thereafter to 24 months
|
Odds ratio (OR) per month of back pain Often, Usually, or Always (vs.
Never, Rarely, Sometimes) estimated with a repeated measures analysis (baseline, 1 month, 3 months and every 3 months thereafter to 24 months) using a generalized linear mixed model.
|
Baseline, 1 month, 3 months and every 3 months thereafter to 24 months
|
Estimated Glomerular Filtration Rate (eGFR)
Time Frame: Baseline, 2 weeks, and 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 months
|
Mean change to 24 months, estimated with a repeated measures analysis (baseline, 2 weeks, 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 months) using a linear mixed model.
|
Baseline, 2 weeks, and 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 months
|
Total Kidney Volume From Magnetic Resonance Imaging
Time Frame: Baseline, 6 months, 12 months, 18 months, 24 months
|
Annual percent change of height adjusted and natural log transformed total kidney volume [ln(htTKV)] was estimated with a linear mixed model.
|
Baseline, 6 months, 12 months, 18 months, 24 months
|
Total Kidney Cyst Volume From Magnetic Resonance Imaging
Time Frame: Baseline, 6 months, 12 months, 18 months, 24 months
|
Annual percent change of height adjusted and natural log transformed total kidney cyst volume [ln(htTKCV)] was estimated with a linear mixed model.
|
Baseline, 6 months, 12 months, 18 months, 24 months
|
Liver Volume From Magnetic Resonance Imaging
Time Frame: Baseline, 6 months, 12 months, 18 months, 24 months
|
Annual percent change of height adjusted and natural log transformed liver volume [ln(htLV)] was estimated with a linear mixed model.
|
Baseline, 6 months, 12 months, 18 months, 24 months
|
Liver Cyst Volume From Magnetic Resonance Imaging
Time Frame: Baseline, 6 months, 12 months, 18 months, 24 months
|
Annual percent change of height adjusted and natural log transformed liver cyst volume [ln(htLCV)] was estimated with a linear mixed model.
|
Baseline, 6 months, 12 months, 18 months, 24 months
|
Frequency Abdominal Fullness Interfered With Ability to Perform Usual Physical Activity Over the Past 3 Months Since Last Visit.
Time Frame: Baseline, 1 month, 3 months and every 3 months thereafter to 24 months
|
Odds ratio (OR) per month of abdominal fullness interfered Often, Usually, or Always (vs.
Never, Rarely, Sometimes) estimated with a repeated measures analysis (baseline, 1 month, 3 months and every 3 months thereafter to 24 months) using a generalized linear mixed model.
|
Baseline, 1 month, 3 months and every 3 months thereafter to 24 months
|
Interference of Pain With Sleep Over the Past 3 Months Since Last Visit
Time Frame: Baseline, 1 month, 3 months and every 3 months thereafter to 24 months
|
Odds ratio (OR) per month of pain interfered with sleep Quite a bit or Extremely (vs.
Not at all, A little bit, Moderately) estimated with a repeated measures analysis (baseline, 1 month, 3 months and every 3 months thereafter to 24 months) using a generalized linear mixed model.
|
Baseline, 1 month, 3 months and every 3 months thereafter to 24 months
|
Interference of Pain With Strenuous Physical Activity Over the Past 3 Months Since Last Visit
Time Frame: Baseline, 1 month, 3 months and every 3 months thereafter to 24 months
|
Odds ratio (OR) per month of pain interfered with strenuous physical activity Quite a bit or Extremely (vs.
Not at all, A little bit, Moderately) estimated with a repeated measures analysis (baseline, 1 month, 3 months and every 3 months thereafter to 24 months) using a generalized linear mixed model.
|
Baseline, 1 month, 3 months and every 3 months thereafter to 24 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Kyongtae Bae, MD, PhD, University of Pittsburgh
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Urologic Diseases
- Congenital Abnormalities
- Genetic Diseases, Inborn
- Joint Diseases
- Musculoskeletal Diseases
- Muscular Diseases
- Musculoskeletal Abnormalities
- Abnormalities, Multiple
- Kidney Diseases, Cystic
- Ciliopathies
- Kidney Diseases
- Polycystic Kidney Diseases
- Polycystic Kidney, Autosomal Dominant
- Arthrogryposis
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Metformin
Other Study ID Numbers
- PRO15060422
- CDMRP-PR141606 (Other Identifier: US Army Medical Research and Materiel Command)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Polycystic Kidney, Autosomal Dominant
-
Emory UniversityPKD FoundationCompleted
-
Mayo ClinicNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Recruiting
-
Mario Negri Institute for Pharmacological ResearchOtsuka Pharmaceutical Italy S.r.l.CompletedAutosomal Dominant Polycystic Kidney DiseaseItaly
-
Mayo ClinicUniversity of Kansas Medical CenterCompletedAutosomal Dominant Polycystic Kidney DiseaseUnited States
-
CHU de ReimsCompletedAutosomal Dominant Polycystic Kidney DiseaseFrance
-
Otsuka Pharmaceutical Development & Commercialization...CompletedAutosomal Dominant Polycystic Kidney DiseaseUnited States
-
Regional Hospital HolstebroAarhus University HospitalCompletedAutosomal Dominant Polycystic Kidney DiseaseDenmark
-
University Hospital, BrestUnknownAutosomal Dominant Polycystic Kidney DiseaseFrance
-
Federico II UniversityCompletedAutosomal Dominant Polycystic Kidney Disease
-
Kadmon Corporation, LLCTerminatedAutosomal Dominant Polycystic Kidney Disease (ADPKD)United States
Clinical Trials on Metformin
-
Anji PharmaSuspendedDiabetes Mellitus, Type 2Spain, United States, Canada, Hungary, Brazil, Czechia, Poland, Bulgaria
-
ShionogiCompleted
-
NuSirt BiopharmaCompletedType 2 Diabetes MellitusUnited States
-
Bristol-Myers SquibbCompletedType 2 Diabetes MellitusSouth Africa, United States, Canada, Puerto Rico, Hungary, Germany, Czechia, Poland, Romania, United Kingdom
-
Charles University, Czech RepublicCompleted
-
Hoffmann-La RocheCompletedDiabetes Mellitus Type 2United States, Mexico, Argentina
-
Hadassah Medical OrganizationWithdrawn
-
Woman'sPfizer; American Cancer Society, Inc.; Our Lady of the Lake Regional Medical...WithdrawnInsulin Resistance | Breast Cancer Stage | Racial BiasUnited States
-
Garvan Institute of Medical ResearchWeizmann Institute of ScienceActive, not recruitingType 2 Diabetes Mellitus | Pre DiabetesAustralia
-
University Hospital, Basel, SwitzerlandCompletedBecker's Muscular Dystrophy (BMD)Switzerland