Endogenous Renin-Angiotensin-Aldosterone System and Glucose Metabolism

• 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: Vanderbilt University Medical Center
• Information provided by (Responsible Party): James Matt Luther, Vanderbilt University Medical Center

Tracking Information

• First Submitted Date: January 9, 2014
• First Posted Date: January 13, 2014
• Results First Submitted Date: December 6, 2020
• Results First Posted Date: December 31, 2020
• Last Update Posted Date: January 20, 2021
• Actual Study Start Date: October 2013
• Actual Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (submitted: January 10, 2014): Insulin Secretion [ Time Frame: After 8 days of diet ]
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures (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: Endogenous Renin-Angiotensin-Aldosterone System and Glucose Metabolism
• Official Title: 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: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Basic Science
• Condition: Metabolic Syndrome

Intervention

• 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

• 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

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 6, 2020): 44
• Original Estimated Enrollment (submitted: January 10, 2014): 57
• Actual Study Completion Date: December 2019
• Actual Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02034435
• Other Study ID Numbers: 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: Not Provided
• Responsible Party: James Matt Luther, Vanderbilt University Medical Center
• Study Sponsor: Vanderbilt University Medical Center
• Collaborators: Not Provided

Investigators

• Principal Investigator: James M Luther, MD; Vanderbilt University Medical Center

• PRS Account: Vanderbilt University Medical Center
• Verification Date: December 2020