Aldosterone and the Metabolic Syndrome

Diabetes Mellitus Clinical Trial

Official title:

Aldosterone and the Metabolic Syndrome: Renin Inhibition Versus Mineralocorticoid Receptor (MR) Antagonism

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01103245
• Other study ID #: 091072
• Secondary ID: 09CRP2261428
• Status: Completed
• Phase: Phase 1
• Start date: March 2010
• Est. completion date: September 2013

Study information

• Verified date: March 2018
• Source: Vanderbilt University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: September 2013
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Endocrine System Diseases
• Glucose Metabolism Disorders
• Metabolic Diseases
• Metabolic Syndrome X

Intervention

Drug:
• Hydrochlorothiazide (HCTZ)
HCTZ 12.5mg daily
• Aliskiren 150 mg (ALI 150)
Aliskiren 150mg daily
• Spironolactone (SPL 25)
spironolactone 25mg daily
• Aliskiren 300 mg (ALI 300)
Aliskiren 300mg daily
• Spironolactone 50 mg (SPL 50)
Spironolactone 50 mg daily

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	at the end of each 1 month study period ( 3 times in total)
Primary	Plasma Glucose	Fasting plasma glucose, measured during hyperglycemic clamp	at the end of each 1 month study period ( 3 times in total)