Endogenous Renin-Angiotensin-Aldosterone System and Glucose Metabolism

Metabolic Syndrome Clinical Trial

Official title:

Endogenous Renin-Angiotensin-Aldosterone System and Glucose Metabolism

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02034435
• Other study ID #: 131139
• Status: Completed
• Phase: Phase 4
• Start date: October 2013
• Est. completion date: December 2019

Study information

• Verified date: December 2020
• Source: Vanderbilt University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: December 2019
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Metabolic Syndrome

Intervention

Other:
• Low Salt diet plus Placebo tablet

• Low Sodium diet plus Salt tablet

Drug:
• Epleronone
50mg daily
• Amlodipine
5mg daily

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insulin Secretion	Hyperglycemic clamp- acute insulin response (AIR) during time 0-10 minutes	After 8 days of diet or drug
Primary	Insulin Sensitivity	Hyperinsulinemic clamp- glucose infusion rate during insulin administration	after 8 days of diet or medication