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Endogenous Renin-Angiotensin-Aldosterone System and Glucose Metabolism

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

Study Description
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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.


Condition or disease Intervention/treatment Phase
Metabolic Syndrome Other: Low Salt diet plus Placebo tablet Other: Low Sodium diet plus Salt tablet Drug: Epleronone Drug: Amlodipine Phase 4

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 44 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: Endogenous Renin-Angiotensin-Aldosterone System and Glucose Metabolism
Actual Study Start Date : October 2013
Actual Primary Completion Date : December 2019
Actual Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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.

 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.

 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.
 Other: Low Salt diet plus Placebo tablet
Drug: Epleronone
50mg daily
Other Name: Inspra

Drug: Amlodipine
5mg daily
Other Name: Norvasc
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.
 Other: Low Salt diet plus Placebo tablet
Drug: Epleronone
50mg daily
Other Name: Inspra

Drug: Amlodipine
5mg daily
Other Name: Norvasc


Outcome Measures
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Primary Outcome Measures :
  1. Insulin Secretion [ Time Frame: After 8 days of diet or drug ]
    Hyperglycemic clamp- acute insulin response (AIR) during time 0-10 minutes

  2. Insulin Sensitivity [ Time Frame: after 8 days of diet or medication ]
    Hyperinsulinemic clamp- glucose infusion rate during insulin administration


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02034435


Locations
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United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232-6602
Sponsors and Collaborators
Vanderbilt University Medical Center
Investigators
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Principal Investigator: James M Luther, MD Vanderbilt University Medical Center
  Study Documents (Full-Text)

Documents provided by James Matt Luther, Vanderbilt University Medical Center:
Study Protocol and Statistical Analysis Plan  [PDF] October 4, 2016

More Information
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Responsible Party: James Matt Luther, M.D., MSCI, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier: NCT02034435    
Other Study ID Numbers: 131139
First Posted: January 13, 2014    Key Record Dates
Results First Posted: December 31, 2020
Last Update Posted: January 20, 2021
Last Verified: December 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Metabolic Syndrome
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Amlodipine
Antihypertensive Agents
 Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Vasodilator Agents