Metformin as a Novel Therapy for Autosomal Dominant Polycystic Kidney Disease (TAME)

August 6, 2022 updated by: Kyongtae Ty Bae, M.D., Ph.D.
This study will test to see if metformin is safe and if it is tolerated compared to placebo in adult Autosomal Dominant Polycystic Kidney Disease (ADPKD) patients with beginning stages of chronic kidney disease. We will also measure its effect on progression of kidney disease as reflected in the kidney size and the kidney function, along with its effect on kidney pain and quality of life.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

There is growing evidence that metformin, a drug widely used for the treatment of type 2 diabetes and polycystic ovary syndrome, may serve as a novel therapy for individuals in the early stages of Autosomal Dominant Polycystic Kidney Disease ADPKD by activating the metabolic sensor AMP-activated protein kinase (AMPK). AMPK is activated under conditions of metabolic and other cellular stresses. Through its actions on downstream mediators, AMPK activation during low energy states decreases cellular energy consumption while stimulating energy generating pathways. It has been shown that AMPK phosphorylates and inhibits cystic fibrosis transmembrane conductance regulator (CFTR), thus suppressing epithelial fluid and electrolyte secretion. Similarly, AMPK phosphorylates the tuberin protein, leading to indirect inhibition of the mTOR pathway. Thus, AMPK inhibits both CFTR and mTOR, suggesting that targeted activation of this kinase by metformin may provide a therapeutic benefit in ADPKD. It has been shown that metformin treatment of kidney epithelial cells leads to stimulation of AMPK and subsequent inhibition of both mTOR and CFTR activity. It has also been shown that metformin slows cystogenesis in animal models of PKD, supporting the potential of this drug in ADPKD treatment.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
97

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
        • Tufts Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Metformin

Participants will be started on 500 mg of metformin once daily, with the following scheduled dose titrations:

  • Increase to 500mg twice daily at week 2
  • Increase to 1000mg qAM, 500mg qPM at week 4

  • Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).

    • Increased titrations based on tolerability
Drug: Metformin
Monitoring of tolerability and symptoms.
Other Names:
  • Glucophage
  • Metformin hydrochloride
Placebo Comparator: Placebo

Participants will be started on 500 mg of placebo once daily, with the following scheduled dose titrations:

  • Increase to 500mg twice daily at week 2
  • Increase to 1000mg qAM, 500mg qPM at week 4

  • Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).

    • Increased titrations based on tolerability
Other: Placebo
Monitoring of tolerability and symptoms.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Kyongtae Ty Bae, M.D., Ph.D.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of Maryland, Baltimore
United States Department of Defense
University of Southern California
Tufts Medical Center

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Kyongtae Bae, MD, PhD, University of Pittsburgh

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 27, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 7, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 7, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 23, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 12, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 14, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 9, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 6, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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)?

No

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

Clinical Trials on Metformin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings