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Aldosterone and the Metabolic Syndrome

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ClinicalTrials.gov Identifier: NCT01103245
Recruitment Status : Completed
First Posted : April 14, 2010
Results First Posted : November 5, 2018
Last Update Posted : November 5, 2018
Sponsor:
Information provided by (Responsible Party):
James Matt Luther, Vanderbilt University Medical Center

Brief Summary:
The purpose of this study is to determine the effects of mineralocorticoid receptor (MR) antagonism and renin inhibition on glucose metabolism in humans.

Condition or disease Intervention/treatment Phase
Metabolic Diseases Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Drug: Hydrochlorothiazide (HCTZ) Drug: Aliskiren 150 mg (ALI 150) Drug: Spironolactone (SPL 25) Drug: Aliskiren 300 mg (ALI 300) Drug: Spironolactone 50 mg (SPL 50) Phase 1

Detailed Description:
The purpose of this study is to determine the effects of mineralocorticoid receptor (MR) antagonism and renin inhibition on fasting blood glucose and glucose-stimulated insulin secretion in humans.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 69 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Aldosterone and the Metabolic Syndrome: Renin Inhibition Versus Mineralocorticoid Receptor (MR) Antagonism
Study Start Date : March 2010
Actual Primary Completion Date : July 2012
Actual Study Completion Date : September 2013


Arm Intervention/treatment
Active Comparator: HCTZ plus ALI 150 then ALI 300

Hydrochlorothiazide (HCTZ) 12.5mg daily for 1 month

then HCTZ 12.5mg daily plus Aliskiren 150 mg (ALI 150) daily for 1 month

then HCTZ 12.5mg daily plus Aliskiren 300mg ((ALI 300) for 1 month

Drug: Hydrochlorothiazide (HCTZ)
HCTZ 12.5mg daily
Other Name: HCTZ

Drug: Aliskiren 150 mg (ALI 150)
Aliskiren 150mg daily
Other Name: Tekturna

Drug: Aliskiren 300 mg (ALI 300)
Aliskiren 300mg daily
Other Name: Tekturna

Active Comparator: HCTZ plus ALI 150 then ALI 150 and SPL 25

HCTZ 12.5mg daily for 1 month

then HCTZ 12.5mg daily plus Aliskiren 150 mg daily for 1 month

then HCTZ 12.5mg daily plus Aliskiren 150 mg daily and Spironolactone 25mg (SPL 25) daily for one month

Drug: Hydrochlorothiazide (HCTZ)
HCTZ 12.5mg daily
Other Name: HCTZ

Drug: Aliskiren 150 mg (ALI 150)
Aliskiren 150mg daily
Other Name: Tekturna

Drug: Spironolactone (SPL 25)
spironolactone 25mg daily
Other Name: Aldactone

Active Comparator: HCTZ plus SPL 25 then SPL 50

HCTZ 12.5mg daily for 1 month

then HCTZ 12.5mg daily plus Spironolactone 25 mg (SPL 25) daily for 1 month

then HCTZ 12.5mg daily plus Spironolactone 50 mg daily for one month

Drug: Hydrochlorothiazide (HCTZ)
HCTZ 12.5mg daily
Other Name: HCTZ

Drug: Spironolactone (SPL 25)
spironolactone 25mg daily
Other Name: Aldactone

Drug: Spironolactone 50 mg (SPL 50)
Spironolactone 50 mg daily
Other Name: Aldactone

Active Comparator: HCTZ plus SPL 25 then ALI 150 and SPL 25

HCTZ 12.5mg daily for 1 month

then HCTZ 12.5mg daily plus Spironolactone 25 mg daily for 1 month

then HCTZ 12.5mg daily plus Aliskiren 150 mg daily and Spironolactone 25 mg daily for one month

Drug: Hydrochlorothiazide (HCTZ)
HCTZ 12.5mg daily
Other Name: HCTZ

Drug: Aliskiren 150 mg (ALI 150)
Aliskiren 150mg daily
Other Name: Tekturna

Drug: Spironolactone (SPL 25)
spironolactone 25mg daily
Other Name: Aldactone




Primary Outcome Measures :
  1. Plasma Insulin [ Time Frame: at the end of each 1 month study period ( 3 times in total) ]
    A Hyperglycemic clamp was performed once during each study period to assess glucose stimulated insulin secretion. Glucose is infused intravenously to maintain blood glucose near 200 mg/dL to stimulate insulin secretion. During this time plasma insulin levels were measured and the insulin response is reported as the incremental increase over the first 10 minutes of glucose administration.

  2. Plasma Glucose [ Time Frame: at the end of each 1 month study period ( 3 times in total) ]
    Fasting plasma glucose, measured during hyperglycemic clamp



Information from the National Library of Medicine

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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:

  • Subjects meeting all of the following conditions will be included in the study:

    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. A seated or supine systolic blood pressure greater than 130/85 on three separate measurements at least 15 minutes apart
    4. Metabolic Syndrome as defined by the presence of > 3 of the following:

      1. Hypertension as characterized by having Systolic Blood Pressure > 140 mm Hg and Diastolic Blood Pressure > 90 mm Hg.
      2. Impaired Glucose Tolerance (Fasting Plasma Glucose > 100 mg/dL)
      3. Increased triglyceride level > 150mg/dL
      4. Decreased levels of High-Density Lipoprotein (HDL) cholesterol

        1. For males, less than 30 mg/dL
        2. For females, less than 40 mg/dL
      5. Waist circumference

        1. For males, greater than 40 inches.
        2. For females, greater than 35 inches.

Exclusion Criteria:

  • Subjects presenting with any of the following will not be included in the study:

    1. Diabetes type 1 or type 2, a fasting glucose of greater than 110 mg/dL or the use of anti-diabetic medication
    2. Use of hormone replacement therapy
    3. Statin therapy
    4. Pregnancy
    5. Breast-feeding
    6. Cardiovascular disease such as prior myocardial infarction, presence of angina pectoris, significant arrhythmia, congestive heart failure [Left Ventricular (LV) hypertrophy acceptable], deep vein thrombosis, pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis or hypertrophic cardiomyopathy
    7. Treatment with anticoagulants
    8. History of serious neurologic disease such as cerebral hemorrhage, stroke, seizure, or transient ischemic attack
    9. History or presence of immunological or hematological disorders
    10. Diagnosis of asthma requiring use of inhaled beta agonist >1 time per week
    11. Clinically significant gastrointestinal impairment that could interfere with drug absorption
    12. Impaired hepatic function [aspartate amino transaminase (AST) and/or alanine amino transaminase (ALT) >1.5 x upper limit of normal range]
    13. Impaired renal function [estimated glomerular filtration rate (eGFR) of <60ml/min] as determined by the four-variable Modification of Diet in Renal Disease (MDRD) equation, where serum creatinine (Scr) is expressed in mg/dl and age in years:

      eGFR (ml/min/1.73m2)=175 • Scr-1.154 • age-0.203 • (1.212 if black) • (0.742 if female)

    14. Hematocrit <35%
    15. 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
    16. Treatment with chronic systemic glucocorticoid therapy (more than 7 consecutive days in 1 month)
    17. Treatment with lithium salts
    18. History of alcohol or drug abuse
    19. Treatment with any investigational drug in the 1 month preceding the study
    20. Mental conditions rendering the subject unable to understand the nature, scope and possible consequences of the study
    21. Inability to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study
    22. Screening plasma potassium <3.2 mmol/L or use of chronic potassium supplements for the treatment of hypokalemia

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): NCT01103245


Locations
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University Medical Center
Investigators
Principal Investigator: James M Luther, MD Vanderbilt University

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: James Matt Luther, Assistant Professor of Medicine, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier: NCT01103245     History of Changes
Other Study ID Numbers: 091072
09CRP2261428 ( Other Grant/Funding Number: American Heart Association )
First Posted: April 14, 2010    Key Record Dates
Results First Posted: November 5, 2018
Last Update Posted: November 5, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by James Matt Luther, Vanderbilt University Medical Center:
Glucose
Insulin

Additional relevant MeSH terms:
Diabetes Mellitus
Metabolic Syndrome X
Metabolic Diseases
Glucose Metabolism Disorders
Endocrine System Diseases
Insulin Resistance
Hyperinsulinism
Hydrochlorothiazide
Spironolactone
Antihypertensive Agents
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Diuretics, Potassium Sparing