Endogenous Renin-Angiotensin-Aldosterone System and Glucose Metabolism

NCT02034435 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: 131139
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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.

Conditions

Metabolic Syndrome

Outcome Measures

Primary Outcomes (2)

• Insulin Secretion

  Hyperglycemic clamp- acute insulin response (AIR) during time 0-10 minutes

  After 8 days of diet or drug

• Insulin Sensitivity

  Hyperinsulinemic clamp- glucose infusion rate during insulin administration

  after 8 days of diet or medication

Study Arms (4)

Aim1-Low Sodium then High Sodium

ACTIVE COMPARATOR

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.

Other: Low Salt diet plus Placebo tablet; Other: Low Sodium diet plus Salt tablet

Aim 1-high salt diet then low salt diet

ACTIVE COMPARATOR

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.

Other: Low Salt diet plus Placebo tablet; Other: Low Sodium diet plus Salt tablet

Aim2- low salt diet and epleronone then amlodipine

ACTIVE COMPARATOR

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.

Other: Low Salt diet plus Placebo tablet; Drug: Epleronone; Drug: Amlodipine

aim2- low salt diet and amlodipine then epleronone

ACTIVE COMPARATOR

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.

Other: Low Salt diet plus Placebo tablet; Drug: Epleronone; Drug: Amlodipine

Interventions

Low Salt diet plus Placebo tablet OTHER

Aim 1-high salt diet then low salt diet; Aim1-Low Sodium then High Sodium; Aim2- low salt diet and epleronone then amlodipine; aim2- low salt diet and amlodipine then epleronone

Low Sodium diet plus Salt tablet OTHER

Aim 1-high salt diet then low salt diet; Aim1-Low Sodium then High Sodium

Epleronone DRUG

50mg daily

Also known as: Inspra

Aim2- low salt diet and epleronone then amlodipine; aim2- low salt diet and amlodipine then epleronone

Amlodipine DRUG

5mg daily

Also known as: Norvasc

Aim2- low salt diet and epleronone then amlodipine; aim2- low salt diet and amlodipine then epleronone

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ambulatory subjects, 18 to 70 years of age, inclusive
• For female subjects, the following conditions must be met:
• postmenopausal status for at least 1 year, or
• status-post surgical sterilization, or
• 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.
• Metabolic Syndrome as defined by the presence of \> 3 of the following:
• Systolic Blood Pressure \> 130 mm Hg OR Diastolic Blood Pressure \> 85 mm Hg.
• Glucose Intolerance (Fasting Plasma Glucose ≥ 100 mg/dL)
• Increased triglyceride level \> 150mg/dL (1.7mmol/L)
• Decreased levels of HDL cholesterol (For males, less than 40 mg/dL; For females, less than 50 mg/dL)
• Waist circumference (For males, greater than 40 inches; For females, greater than 35 inches)

You may not qualify if:

• type 1 Diabetes
• Type II Diabetes
• Impaired renal function
• Prior allergies to medications used in the study protocol
• Screening plasma potassium \>5.5 mmol/L or sodium \<135 mmol/L
• Cardiovascular disease
• Use of hormone replacement therapy
• Breast-feeding
• Treatment with anticoagulants
• History of serious neurologic disease
• History or presence of immunological or hematological disorders
• Diagnosis of asthma requiring use of inhaled beta agonist
• Clinically significant gastrointestinal impairment
• Impaired hepatic function
• Hematocrit \<35%

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232-6602, United States

Location

MeSH Terms

Conditions

Metabolic Syndrome

Interventions

Diet, Sodium-Restricted; Salts; Eplerenone; Amlodipine

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Inorganic Chemicals; Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. James M. Luther, MD
• Organization: Vanderbilt University Medical Center

james.luther@vumc.org

(615) 936-3420

Study Officials

• James M Luther, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D., MSCI

Study Record Dates

• First Submitted: January 9, 2014
• First Posted: January 13, 2014
• Study Start: October 1, 2013
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: January 20, 2021
• Results First Posted: December 31, 2020

Record last verified: 2020-12

Locations

US (1)