search
Back to results

Aldosterone and the Metabolic Syndrome

Primary Purpose

Metabolic Diseases, Diabetes Mellitus, Endocrine System Diseases

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Hydrochlorothiazide (HCTZ)
Aliskiren 150 mg (ALI 150)
Spironolactone (SPL 25)
Aliskiren 300 mg (ALI 300)
Spironolactone 50 mg (SPL 50)
Sponsored by
Vanderbilt University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Metabolic Diseases focused on measuring Glucose, Insulin

Eligibility Criteria

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

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

Sites / Locations

  • Vanderbilt University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Arm Label

HCTZ plus ALI 150 then ALI 300

HCTZ plus ALI 150 then ALI 150 and SPL 25

HCTZ plus SPL 25 then SPL 50

HCTZ plus SPL 25 then ALI 150 and SPL 25

Arm Description

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

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

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

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

Outcomes

Primary Outcome Measures

Plasma Insulin
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.
Plasma Glucose
Fasting plasma glucose, measured during hyperglycemic clamp

Secondary Outcome Measures

Full Information

First Posted
April 12, 2010
Last Updated
March 26, 2018
Sponsor
Vanderbilt University Medical Center
search

1. Study Identification

Unique Protocol Identification Number
NCT01103245
Brief Title
Aldosterone and the Metabolic Syndrome
Official Title
Aldosterone and the Metabolic Syndrome: Renin Inhibition Versus Mineralocorticoid Receptor (MR) Antagonism
Study Type
Interventional

2. Study Status

Record Verification Date
March 2018
Overall Recruitment Status
Completed
Study Start Date
March 2010 (undefined)
Primary Completion Date
July 2012 (Actual)
Study Completion Date
September 2013 (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
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metabolic Diseases, Diabetes Mellitus, Endocrine System Diseases, Glucose Metabolism Disorders
Keywords
Glucose, Insulin

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
69 (Actual)

8. Arms, Groups, and Interventions

Arm Title
HCTZ plus ALI 150 then ALI 300
Arm Type
Active Comparator
Arm Description
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
Arm Title
HCTZ plus ALI 150 then ALI 150 and SPL 25
Arm Type
Active Comparator
Arm Description
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
Arm Title
HCTZ plus SPL 25 then SPL 50
Arm Type
Active Comparator
Arm Description
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
Arm Title
HCTZ plus SPL 25 then ALI 150 and SPL 25
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Hydrochlorothiazide (HCTZ)
Other Intervention Name(s)
HCTZ
Intervention Description
HCTZ 12.5mg daily
Intervention Type
Drug
Intervention Name(s)
Aliskiren 150 mg (ALI 150)
Other Intervention Name(s)
Tekturna
Intervention Description
Aliskiren 150mg daily
Intervention Type
Drug
Intervention Name(s)
Spironolactone (SPL 25)
Other Intervention Name(s)
Aldactone
Intervention Description
spironolactone 25mg daily
Intervention Type
Drug
Intervention Name(s)
Aliskiren 300 mg (ALI 300)
Other Intervention Name(s)
Tekturna
Intervention Description
Aliskiren 300mg daily
Intervention Type
Drug
Intervention Name(s)
Spironolactone 50 mg (SPL 50)
Other Intervention Name(s)
Aldactone
Intervention Description
Spironolactone 50 mg daily
Primary Outcome Measure Information:
Title
Plasma Insulin
Description
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.
Time Frame
at the end of each 1 month study period ( 3 times in total)
Title
Plasma Glucose
Description
Fasting plasma glucose, measured during hyperglycemic clamp
Time Frame
at the end of each 1 month study period ( 3 times in total)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects meeting all of the following conditions will be included in the study: 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. A seated or supine systolic blood pressure greater than 130/85 on three separate measurements at least 15 minutes apart Metabolic Syndrome as defined by the presence of > 3 of the following: Hypertension as characterized by having Systolic Blood Pressure > 140 mm Hg and Diastolic Blood Pressure > 90 mm Hg. Impaired Glucose Tolerance (Fasting Plasma Glucose > 100 mg/dL) Increased triglyceride level > 150mg/dL Decreased levels of High-Density Lipoprotein (HDL) cholesterol For males, less than 30 mg/dL For females, less than 40 mg/dL Waist circumference For males, greater than 40 inches. For females, greater than 35 inches. Exclusion Criteria: Subjects presenting with any of the following will not be included in the study: Diabetes type 1 or type 2, a fasting glucose of greater than 110 mg/dL or the use of anti-diabetic medication Use of hormone replacement therapy Statin therapy Pregnancy Breast-feeding 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 Treatment with anticoagulants History of serious neurologic disease such as cerebral hemorrhage, stroke, seizure, or transient ischemic attack History or presence of immunological or hematological disorders Diagnosis of asthma requiring use of inhaled beta agonist >1 time per week Clinically significant gastrointestinal impairment that could interfere with drug absorption Impaired hepatic function [aspartate amino transaminase (AST) and/or alanine amino transaminase (ALT) >1.5 x upper limit of normal range] 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) 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 (more than 7 consecutive days in 1 month) Treatment with lithium salts History of alcohol or drug abuse Treatment with any investigational drug in the 1 month preceding the study 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 Screening plasma potassium <3.2 mmol/L or use of chronic potassium supplements for the treatment of hypokalemia
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James M Luther, MD
Organizational Affiliation
Vanderbilt University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
25173047
Citation
Ramirez CE, Shuey MM, Milne GL, Gilbert K, Hui N, Yu C, Luther JM, Brown NJ. Arg287Gln variant of EPHX2 and epoxyeicosatrienoic acids are associated with insulin sensitivity in humans. Prostaglandins Other Lipid Mediat. 2014 Oct;113-115:38-44. doi: 10.1016/j.prostaglandins.2014.08.001. Epub 2014 Aug 28.
Results Reference
derived

Learn more about this trial

Aldosterone and the Metabolic Syndrome

We'll reach out to this number within 24 hrs