Endogenous Renin-Angiotensin-Aldosterone System and Glucose Metabolism

NCT ID: NCT02034435

Last Updated: 2021-01-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-31
• Study Completion Date: 2019-12-31

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.

Conditions

Metabolic Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Low Salt diet plus Placebo tablet

Intervention Type: OTHER

Low Sodium diet plus Salt tablet

Intervention Type: OTHER

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.

Group Type: ACTIVE_COMPARATOR

Low Salt diet plus Placebo tablet

Intervention Type: OTHER

Low Sodium diet plus Salt tablet

Intervention Type: OTHER

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.

Group Type: ACTIVE_COMPARATOR

Low Salt diet plus Placebo tablet

Intervention Type: OTHER

Epleronone

Intervention Type: DRUG

50mg daily

Amlodipine

Intervention Type: DRUG

5mg daily

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.

Group Type: ACTIVE_COMPARATOR

Low Salt diet plus Placebo tablet

Intervention Type: OTHER

Epleronone

Intervention Type: DRUG

50mg daily

Amlodipine

Intervention Type: DRUG

5mg daily

Interventions

Low Salt diet plus Placebo tablet

Intervention Type: OTHER

Low Sodium diet plus Salt tablet

Intervention Type: OTHER

Epleronone

50mg daily

Intervention Type: DRUG

Amlodipine

5mg daily

Intervention Type: DRUG

Other Intervention Names

Inspra; Norvasc

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vanderbilt University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

James Matt Luther

M.D., MSCI

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

James M Luther, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

131139

Identifier Type: -

Identifier Source: org_study_id