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Endogenous Renin-Angiotensin-Aldosterone System and Glucose Metabolism

Primary Purpose

Metabolic Syndrome

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Low Salt diet plus Placebo tablet

Low Sodium diet plus Salt tablet

Epleronone

Amlodipine

About this trial

This is an interventional basic science trial for Metabolic Syndrome

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Ambulatory subjects, 18 to 70 years of age, inclusive
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.
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:

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%
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
Treatment with chronic systemic glucocorticoid therapy
Treatment with lithium salts
History of alcohol or drug abuse
Treatment with any investigational drug in the 1 month preceding
Mental conditions rendering the subject unable to understand the nature, scope and possible consequences of the study
Inability to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study

Sites / Locations

Vanderbilt University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Arm Label

Aim1-Low Sodium then High Sodium

Aim 1-high salt diet then low salt diet

Aim2- low salt diet and epleronone then amlodipine

aim2- low salt diet and amlodipine then epleronone

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Insulin Secretion

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

Insulin Sensitivity

Hyperinsulinemic clamp- glucose infusion rate during insulin administration

Secondary Outcome Measures

Full Information

NCT ID

NCT02034435

First Posted

January 9, 2014

Last Updated

December 30, 2020

Sponsor

Vanderbilt University Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT02034435

Brief Title

Endogenous Renin-Angiotensin-Aldosterone System and Glucose Metabolism

Official Title

Endogenous Renin-Angiotensin-Aldosterone System and Glucose Metabolism

Study Type

Interventional

2. Study Status

Record Verification Date

December 2020

Overall Recruitment Status

Completed

Study Start Date

October 2013 (Actual)

Primary Completion Date

December 2019 (Actual)

Study Completion Date

December 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Vanderbilt University Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metabolic Syndrome

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 4

Interventional Study Model

Crossover Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

44 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Aim1-Low Sodium then High Sodium

Arm Type

Active Comparator

Arm Description

Arm Title

Aim 1-high salt diet then low salt diet

Arm Type

Active Comparator

Arm Description

Arm Title

Aim2- low salt diet and epleronone then amlodipine

Arm Type

Active Comparator

Arm Description

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.

Arm Title

aim2- low salt diet and amlodipine then epleronone

Arm Type

Active Comparator

Arm Description

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.

Intervention Type

Other

Intervention Name(s)

Low Salt diet plus Placebo tablet

Intervention Type

Other

Intervention Name(s)

Low Sodium diet plus Salt tablet

Intervention Type

Drug

Intervention Name(s)

Epleronone

Other Intervention Name(s)

Inspra

Intervention Description

50mg daily

Intervention Type

Drug

Intervention Name(s)

Amlodipine

Other Intervention Name(s)

Norvasc

Intervention Description

5mg daily

Primary Outcome Measure Information:

Title

Insulin Secretion

Description

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

Time Frame

After 8 days of diet or drug

Title

Insulin Sensitivity

Description

Hyperinsulinemic clamp- glucose infusion rate during insulin administration

Time Frame

after 8 days of diet or medication

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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) Exclusion Criteria: 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% 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 Treatment with chronic systemic glucocorticoid therapy Treatment with lithium salts History of alcohol or drug abuse Treatment with any investigational drug in the 1 month preceding Mental conditions rendering the subject unable to understand the nature, scope and possible consequences of the study Inability to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

James M Luther, MD

Organizational Affiliation

Vanderbilt University Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Vanderbilt University Medical Center

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37232-6602

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Endogenous Renin-Angiotensin-Aldosterone System and Glucose Metabolism

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