Aldosterone and the Metabolic Syndrome

NCT01103245 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 09107209CRP2261428
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

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.

Conditions

Metabolic Diseases; Diabetes Mellitus; Endocrine System Diseases; Glucose Metabolism Disorders

Keywords

Glucose; Insulin

Outcome Measures

Primary Outcomes (2)

• 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)

• Plasma Glucose

  Fasting plasma glucose, measured during hyperglycemic clamp

  at the end of each 1 month study period ( 3 times in total)

Study Arms (4)

HCTZ plus ALI 150 then ALI 300

ACTIVE COMPARATOR

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); Drug: Aliskiren 150 mg (ALI 150); Drug: Aliskiren 300 mg (ALI 300)

HCTZ plus ALI 150 then ALI 150 and SPL 25

ACTIVE COMPARATOR

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); Drug: Aliskiren 150 mg (ALI 150); Drug: Spironolactone (SPL 25)

HCTZ plus SPL 25 then SPL 50

ACTIVE COMPARATOR

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); Drug: Spironolactone (SPL 25); Drug: Spironolactone 50 mg (SPL 50)

HCTZ plus SPL 25 then ALI 150 and SPL 25

ACTIVE COMPARATOR

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); Drug: Aliskiren 150 mg (ALI 150); Drug: Spironolactone (SPL 25)

Interventions

Hydrochlorothiazide (HCTZ) DRUG

HCTZ 12.5mg daily

Also known as: HCTZ

HCTZ plus ALI 150 then ALI 150 and SPL 25; HCTZ plus ALI 150 then ALI 300; HCTZ plus SPL 25 then ALI 150 and SPL 25; HCTZ plus SPL 25 then SPL 50

Aliskiren 150 mg (ALI 150) DRUG

Aliskiren 150mg daily

Also known as: Tekturna

HCTZ plus ALI 150 then ALI 150 and SPL 25; HCTZ plus ALI 150 then ALI 300; HCTZ plus SPL 25 then ALI 150 and SPL 25

Spironolactone (SPL 25) DRUG

spironolactone 25mg daily

Also known as: Aldactone

HCTZ plus ALI 150 then ALI 150 and SPL 25; HCTZ plus SPL 25 then ALI 150 and SPL 25; HCTZ plus SPL 25 then SPL 50

Aliskiren 300 mg (ALI 300) DRUG

Aliskiren 300mg daily

Also known as: Tekturna

HCTZ plus ALI 150 then ALI 300

Spironolactone 50 mg (SPL 50) DRUG

Spironolactone 50 mg daily

Also known as: Aldactone

HCTZ plus SPL 25 then SPL 50

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

• 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.

  PMID: 25173047 DERIVED

MeSH Terms

Conditions

Metabolic Diseases; Diabetes Mellitus; Endocrine System Diseases; Glucose Metabolism Disorders; Insulin Resistance

Interventions

Hydrochlorothiazide; aliskiren; Spironolactone

Condition Hierarchy (Ancestors)

Nutritional and Metabolic Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: James M. Luther
• Organization: Vanderbilt University Medical Center

james.luther@vanderbilt.edu

(615) 936-3420

Study Officials

• James M Luther, MD

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: April 12, 2010
• First Posted: April 14, 2010
• Study Start: March 1, 2010
• Primary Completion: July 1, 2012
• Study Completion: September 1, 2013
• Last Updated: November 5, 2018
• Results First Posted: November 5, 2018

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)