Aldosterone and the Metabolic Syndrome

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2011 by Vanderbilt University.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Vanderbilt University
ClinicalTrials.gov Identifier:
NCT01103245
First received: April 12, 2010
Last updated: August 4, 2011
Last verified: August 2011
  Purpose

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


Condition Intervention
Metabolic Diseases
Diabetes Mellitus
Endocrine System Diseases
Glucose Metabolism Disorders
Drug: Renin-Angiotensin-Aldosterone System (RAAS) Activation
Drug: Administration of Aliskiren, Spironolactone, or Placebo
Drug: Increased Dose, Combination, or Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Aldosterone and the Metabolic Syndrome: Renin Inhibition Versus Mineralocorticoid Receptor (MR) Antagonism

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Plasma glucose and insulin concentrations [ Time Frame: 3 hours ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 168
Study Start Date: March 2010
Estimated Study Completion Date: January 2012
Estimated Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Renin-Angiotensin Aldosterone Activation
Renin-Angiotensin-Aldosterone System (RAAS) Activation
Drug: Renin-Angiotensin-Aldosterone System (RAAS) Activation
Subjects will be receive a dose of Hydrochlorothiazide (HCTZ) for 12 weeks and be given a calculated diet during the last 5 days of this period. Serum potassium levels, urine samples, and blood levels of insulin secretion will be measured.
Other Name: HCTZ, Professional Compounding Centers of America (PCCA)
Active Comparator: Aliskiren, Spironolactone, or Placebo
Determination of effects of MR antagonism or renin inhibition.
Drug: Administration of Aliskiren, Spironolactone, or Placebo
Subjects will be receive a dose of Aliskiren, Spironolactone, or placebo for 4 weeks and be given a calculated diet during the last 5 days of this period. Serum potassium levels, urine samples, and blood levels of insulin secretion will be measured.
Other Names:
  • Aliskiren (ALI)- brand name: Tekturna - company: Novartis AG
  • Spironolactone (SPL)- generic brand from PCCA
Active Comparator: Increased Dose, Combination, or Placebo
Determination of effects of MR antagonism and/or renin inhibition.
Drug: Increased Dose, Combination, or Placebo
Subjects will be receive either an increased dose of the present medication (Aliskiren or Spironolactone) or a combination of the two or a placebo for 4 weeks and be given a calculated diet during the last 5 days of this period. Serum potassium levels, urine samples, and blood levels of insulin secretion will be measured.
Other Names:
  • Aliskiren (ALI)- brand name: Tekturna - company: Novartis AG
  • Spironolactone (SPL)- generic brand from PCCA

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01103245

Contacts
Contact: Loretta Byrne, RN 615-322-2105 loretta.byrne@vanderbilt.edu
Contact: James Luther, MD 615-343-8701 james.luther@vanderbilt.edu

Locations
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Loretta Byrne, RN    615-322-2105    loretta.byrne@vanderbilt.edu   
Principal Investigator: James M Luther, MD         
Sub-Investigator: Maneesh C. Kanal, BA         
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: James M Luther, MD Vanderbilt University
  More Information

No publications provided

Responsible Party: James M. Luther, MD, MSCI, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier: NCT01103245     History of Changes
Other Study ID Numbers: 091072, 09CRP2261428
Study First Received: April 12, 2010
Last Updated: August 4, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Vanderbilt University:
Glucose
Insulin

Additional relevant MeSH terms:
Metabolic Diseases
Glucose Metabolism Disorders
Diabetes Mellitus
Endocrine System Diseases
Metabolic Syndrome X
Insulin Resistance
Hyperinsulinism
Mineralocorticoids
Spironolactone
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Aldosterone Antagonists
Hormone Antagonists
Diuretics
Natriuretic Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 24, 2014