Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Metformin in Kidney Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02252081
Recruitment Status : Recruiting
First Posted : September 29, 2014
Last Update Posted : February 18, 2019
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development

Brief Summary:

Chronic kidney disease (CKD) is a major global health problem associated with substantial costs and resource utilization. Currently, CKD affects more than 500 million people worldwide. Patients with CKD have unacceptably high mortality rates due to cardiovascular (CV) causes, which are not entirely explained by traditional CV risk factors. The mortality rates in advanced CKD are six times higher compared to the Medicare population, with CVD accounting for the overwhelming majority of deaths. Insulin resistance (IR) is common in CKD patients and may represent a central link between CKD and the increased CVD risk observed in this population. Insulin resistance may increase CV risk by impairing and worsening endothelial function, increasing reactive oxygen species, and exacerbating systemic inflammation-hence, insulin resistance is considered a "non-traditional CV risk factor" in CKD.

Obesity (defined by a body mass index [BMI] of at least 30 kg/m2) is a major public health problem-the upward trend in obesity prevalence across regions and continents is a worldwide concern. Obesity increases the risk for cardiovascular disease and death. In the general population, obesity hastens death by 9.4 years. Obesity is an independent risk factor for CKD. Besides its contribution to the development of diabetes and hypertension, increased fat mass may also have a direct impact on kidney function.

In spite of the increasing prevalence of both obesity and CKD, the impact of obesity in the CKD population is not known, especially in terms of the exaggerated metabolic disturbances associated with their coexistence. It is highly likely that these two conditions have profound interactions that exaggerate the severity of the metabolic derangements when they coexist, particularly in regards to adipokine dysregulation, the risk of "insulin resistance", and downstream effects on vascular health. The current proposal will attempt to characterize the relative and combined impact of both obesity and CKD on metabolic disturbances, which may aid in risk stratification and identifying specific targets for intervention.

The ultimate goal of this proposal is to understand the relative and combined impact of obesity and CKD on the generation and maintenance of insulin resistance and their impact on cardiovascular health.

Specific Aim 2: To study the effects of metformin, an AMPK activator, on metabolic disturbances associated with obesity and moderate CKD.

S.A.2.a: To test if metformin will improve LAR in obese patients with moderate CKD compared to placebo.

S.A.2.b: To test if metformin will improve markers of systemic inflammation, oxidative stress, endothelial dysfunction in obese patients with moderate CKD compared to placebo.

S.A.2.c: To test if metformin will improve atherosclerosis markers and reduce clinical CVD events in obese patients with moderate CKD compared to placebo.

Hypothesis: The investigators hypothesize that the administration of metformin in obese CKD patients will significantly improve the adipokine profiles-particularly through a reduction in LAR. Additionally, that it will improve systemic inflammation, oxidative stress and endothelial function, which may or may not be mediated by changes in adipokines. Finally, the investigators hypothesize that improvements in these markers of vascular health will translate into reduced arterial stiffness and less clinical CV events


Condition or disease Intervention/treatment Phase
Chronic Kidney Disease Cardiovascular Disease Metabolic Syndrome Drug: metformin Drug: Placebo Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Dysmetabolism of Chronic Kidney Disease and Vascular Health
Actual Study Start Date : October 1, 2014
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Diseases

Arm Intervention/treatment
Active Comparator: metformin
500 to 1500 mg orally per day for 16 weeks if eGFR > 45 ml/min; 500 to 1000 mg orally per day for 16 weeks if eGFR =< 45 ml/min
Drug: metformin
500 to 1500 mg orally per day for 16 weeks if eGFR > 45 ml/min; 500 to 1000 mg orally per day for 16 weeks if eGFR =< 45 ml/min

Placebo Comparator: Placebo
placebo pill(s) orally per day for 16 weeks
Drug: Placebo
placebo pill(s) orally per day for 16 weeks




Primary Outcome Measures :
  1. leptin to adiponectin ratio (LAR) [ Time Frame: baseline and 16 weeks ]
    LAR is an atherosclerotic index


Secondary Outcome Measures :
  1. estimated glomerular filtration rate (eGFR) [ Time Frame: baseline and 16 weeks ]
    eGFR is a measurement of kidney function



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18 years old;
  • Ability to give informed consent;
  • Life expectancy greater than 6 months;
  • Estimated GFR 30-59 ml/min/1.73m^2;
  • Overweight (BMI >=25 to < 30 kg/m^2) or obese (BMI >=30 kg/m^2); or normal (BMI >=18.5 to <25 kg/m^2) if pre-diabetic or insulin resistant.

Exclusion Criteria:

  • Pregnancy or breast feeding;
  • Presence or history of Diabetes Mellitus type I or II
  • History of metformin use or any insulin sensitizer or any drug for the treatment of metabolic syndrome over the last one year;
  • Any acute kidney injury episode in the last 4 months due to the risk of recurrent AKI;
  • Proteinuria of > 5 g in 24 hours determined by a 24 hour urine collection or PCR > 4.5;
  • Uncontrolled hypertension with systolic blood pressure 160 mmHg and diastolic blood pressure 100 mmHg;
  • Patients with new changes to their antihypertensive regimen over the last 1 month;
  • Severe, unstable, or active inflammatory disease; active infection including seropositive HIV, Hepatitis B or C; active connective tissue disorder; or moderate to severe liver disease;
  • Decompensated heart failure;
  • Recent hospitalization or surgical procedure within 1 month prior to the study for any cause;
  • Current active malignancy or cancer history in the prior 5 years (excluding squamous cell and basal cell skin cancers);
  • Known intolerance to the study drug;
  • Patient receiving oral or injected steroids
  • Use of any investigational product or device within 30 days prior to screening, or requirement for any investigational agent prior to completion of all scheduled study assessments;

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02252081


Contacts
Layout table for location contacts
Contact: Adriana M Hung, MD MPH (615) 873-6731 Adriana.Hung@va.gov
Contact: Cindy A Booker (615) 343-5828 cindy.a.booker@vanderbilt.edu

Locations
Layout table for location information
United States, Tennessee
Tennessee Valley Healthcare System Nashville Campus, Nashville, TN Recruiting
Nashville, Tennessee, United States, 37212-2637
Contact: Adriana M Hung, MD MPH    615-873-6731    Adriana.Hung@va.gov   
Contact: Cindy A Booker    (615) 343-5828    cindy.a.booker@vanderbilt.edu   
Principal Investigator: Adriana M Hung, MD MPH         
Sponsors and Collaborators
VA Office of Research and Development
Investigators
Layout table for investigator information
Principal Investigator: Adriana M Hung, MD MPH Tennessee Valley Healthcare System Nashville Campus, Nashville, TN

Study Data/Documents: we have no results yet  This link exits the ClinicalTrials.gov site
Study is currently enrolling

Layout table for additonal information
Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT02252081     History of Changes
Other Study ID Numbers: ENDA-014-13F
1I01CX000982-01A1 ( U.S. NIH Grant/Contract )
First Posted: September 29, 2014    Key Record Dates
Last Update Posted: February 18, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by VA Office of Research and Development:
metformin
cardiovascular disease
Chronic Kidney Disease
Metabolic Syndrome

Additional relevant MeSH terms:
Layout table for MeSH terms
Metabolic Syndrome
Cardiovascular Diseases
Kidney Diseases
Renal Insufficiency, Chronic
Urologic Diseases
Renal Insufficiency
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs