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Endogenous Renin-Angiotensin-Aldosterone System and Glucose Metabolism

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ClinicalTrials.gov Identifier: NCT02034435
Recruitment Status : Completed
First Posted : January 13, 2014
Results First Posted : December 31, 2020
Last Update Posted : January 20, 2021
Sponsor:
Information provided by (Responsible Party):
James Matt Luther, Vanderbilt University Medical Center

Tracking Information
First Submitted Date  ICMJE January 9, 2014
First Posted Date  ICMJE January 13, 2014
Results First Submitted Date  ICMJE December 6, 2020
Results First Posted Date  ICMJE December 31, 2020
Last Update Posted Date January 20, 2021
Actual Study Start Date  ICMJE October 2013
Actual Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 6, 2020)
  • Insulin Secretion [ Time Frame: After 8 days of diet or drug ]
    Hyperglycemic clamp- acute insulin response (AIR) during time 0-10 minutes
  • Insulin Sensitivity [ Time Frame: after 8 days of diet or medication ]
    Hyperinsulinemic clamp- glucose infusion rate during insulin administration
Original Primary Outcome Measures  ICMJE
 (submitted: January 10, 2014)
Insulin Secretion [ Time Frame: After 8 days of diet ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: January 10, 2014)
Insulin sensitivity [ Time Frame: after 8 days of diet ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Endogenous Renin-Angiotensin-Aldosterone System and Glucose Metabolism
Official Title  ICMJE Endogenous Renin-Angiotensin-Aldosterone System and Glucose Metabolism
Brief Summary

Aim 1.Test the hypothesis that activation of the endogenous renin-angiotensin-aldosterone system impairs glycemic control via effects on insulin sensitivity and insulin secretion.

Aim 2. Test the hypothesis that activation of the endogenous renin-angiotensin-aldosterone system impairs insulin secretion and insulin sensitivity via an mineralocorticoid-receptor dependent mechanism.

Detailed Description

In aim 1 subjects are randomized to cross over between an 8 day high salt and 8 day low salt diet and assessments are made.

In aim 2, subjects are randomized to a 2x2 cross over study with an 8 day low salt diet and either eplerenone 50mg or amlodipine 5mg.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Condition  ICMJE Metabolic Syndrome
Intervention  ICMJE
  • Other: Low Salt diet plus Placebo tablet
  • Other: Low Sodium diet plus Salt tablet
  • Drug: Epleronone
    50mg daily
    Other Name: Inspra
  • Drug: Amlodipine
    5mg daily
    Other Name: Norvasc
Study Arms  ICMJE
  • Active Comparator: Aim1-Low Sodium then High Sodium

    Subjects will be provided with a low sodium diet from the Vanderbilt Clinical Research Center that will be controlled for salt content.

    Participants will be given low sodium diet (50mEq/d) and Placebo tablets for 8 days and assessments will be made, washout and then cross over to a low sodium diet (50mEq/d) plus Salt tables (150mEq) for 8days and assessments will be made.

    Interventions:
    • Other: Low Salt diet plus Placebo tablet
    • Other: Low Sodium diet plus Salt tablet
  • Active Comparator: Aim 1-high salt diet then low salt diet

    Subjects will be provided with a diet from the Vanderbilt Clinical Research Center that will be controlled for salt content.

    Participants will be given low sodium diet (50mEq/d) and Salt tables (150mEq) for 8 days and assessments will be made, washout and then cross over to a low sodium diet (50mEq/d) plus Placebo tablets for 8days and assessments will be made.

    Interventions:
    • Other: Low Salt diet plus Placebo tablet
    • Other: Low Sodium diet plus Salt tablet
  • Active Comparator: Aim2- low salt diet and epleronone then amlodipine
    Subjects on a low salt diet will receive Epleronone 50mg for 8 days and assessments will be made, then cross over to a low salt diet with Amlodipine 5mg for 8days and assessments will be made.
    Interventions:
    • Other: Low Salt diet plus Placebo tablet
    • Drug: Epleronone
    • Drug: Amlodipine
  • Active Comparator: aim2- low salt diet and amlodipine then epleronone
    Subjects on a low salt diet will receive Amlodipine 5mg for 8 days and assessments will be made, then cross over to a low salt diet with Epleronone 50mg for 8days and assessments will be made.
    Interventions:
    • Other: Low Salt diet plus Placebo tablet
    • Drug: Epleronone
    • Drug: Amlodipine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 6, 2020)
44
Original Estimated Enrollment  ICMJE
 (submitted: January 10, 2014)
57
Actual Study Completion Date  ICMJE December 2019
Actual Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Ambulatory subjects, 18 to 70 years of age, inclusive
  2. For female subjects, the following conditions must be met:

    1. postmenopausal status for at least 1 year, or
    2. status-post surgical sterilization, or
    3. if of childbearing potential, utilization of adequate birth control and willingness to undergo urine beta-hcg testing prior to drug treatment and on every study day.
  3. Metabolic Syndrome as defined by the presence of > 3 of the following:

    1. Systolic Blood Pressure > 130 mm Hg OR Diastolic Blood Pressure > 85 mm Hg.
    2. Glucose Intolerance (Fasting Plasma Glucose ≥ 100 mg/dL)
    3. Increased triglyceride level > 150mg/dL (1.7mmol/L)
    4. Decreased levels of HDL cholesterol (For males, less than 40 mg/dL; For females, less than 50 mg/dL)
    5. Waist circumference (For males, greater than 40 inches; For females, greater than 35 inches)

Exclusion Criteria:

  1. type 1 Diabetes
  2. Type II Diabetes
  3. Impaired renal function
  4. Prior allergies to medications used in the study protocol
  5. Screening plasma potassium >5.5 mmol/L or sodium <135 mmol/L
  6. Cardiovascular disease
  7. Use of hormone replacement therapy
  8. Breast-feeding
  9. Treatment with anticoagulants
  10. History of serious neurologic disease
  11. History or presence of immunological or hematological disorders
  12. Diagnosis of asthma requiring use of inhaled beta agonist
  13. Clinically significant gastrointestinal impairment
  14. Impaired hepatic function
  15. Hematocrit <35%
  16. Any underlying or acute disease requiring regular medication which could possibly pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult, such as arthritis treated with non-steroidal antiinflammatory drugs
  17. Treatment with chronic systemic glucocorticoid therapy
  18. Treatment with lithium salts
  19. History of alcohol or drug abuse
  20. Treatment with any investigational drug in the 1 month preceding
  21. Mental conditions rendering the subject unable to understand the nature, scope and possible consequences of the study
  22. Inability to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02034435
Other Study ID Numbers  ICMJE 131139
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party James Matt Luther, Vanderbilt University Medical Center
Study Sponsor  ICMJE Vanderbilt University Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: James M Luther, MD Vanderbilt University Medical Center
PRS Account Vanderbilt University Medical Center
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP