Mineralocorticoid Receptor and Obesity Induced Cardiovascular Complications

This study has been completed.

Sponsor:

ClinicalTrials.gov Identifier:

NCT01406015

First Posted: July 29, 2011

Last Update Posted: April 28, 2017

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

Information provided by (Responsible Party):

Rajesh K. Garg, Brigham and Women's Hospital

Purpose

The purpose of this study is to find out if spironolactone, a drug that blocks the action of aldosterone, can make the blood vessels work better in people with obesity. The investigators also want to find out whether spironolactone causes changes in levels of insulin and markers of inflammation.

Condition	Intervention
Obesity Insulin Resistance	Drug: Spironolactone Drug: Placebo


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Triple (Participant, Care Provider, Investigator) Primary Purpose: Prevention
Official Title:	Mineralocorticoid Receptor and Obesity Induced Cardiovascular Complications

Resource links provided by NLM:

Drug Information available for: Spironolactone

U.S. FDA Resources

Further study details as provided by Rajesh K. Garg, Brigham and Women's Hospital:

Primary Outcome Measures:

Change From Baseline in Post-ischemic Dilatation [ Time Frame: Baseline and Week 6 ]
Ultrasonography of the brachial artery was performed to evaluate endothelial function by flow mediated dilatation (FMD) studies. A blood pressure cuff was placed on the participant's upper arm and was compressed for 5 minutes. After release of compression, brachial artery diameter and blood flow velocity were measured. FMD was expressed as the percentage change in brachial artery diameter. A positive change from Baseline indicates improvement.

Secondary Outcome Measures:

Change From Baseline in Para-aminohippurate (PAH) Clearance [ Time Frame: Baseline and Week 6 (Prior to PAH infusion and at 50 and 60 minutes post PAH infusion) ]
Renal plasma blood flow was determined by clearance of para-aminohippurate (PAH). A loading dose of PAH (8 mg/kg) was given intravenously followed by a 1 hour constant infusion of PAH at a rate of 12 mg/minute (min). Plasma samples were obtained at Baseline and at 50 and 60 minutes. PAH clearance was calculated from the plasma levels and infusion rates and reported in millimeters (mL)/minute (min). A positive change from Baseline indicates improvement.
Change From Baseline in Markers of Inflammation [ Time Frame: Baseline and Week 6 ]
Blood was to be collected and tested for Tumor Necrosis Factor Alpha (TNF-α) and Monocyte Chemotactic Protein-1 (MCP-1), markers of inflammation; However, due to lack of funding, blood samples were not analyzed and data for levels of inflammation markers were not collected.
Change From Baseline in Insulin Sensitivity Index (ISI) [ Time Frame: Baseline and Week 6 (Prior to ingesting glucose and every 30 minutes for 120 minutes) ]
Insulin sensitivity was measured using the 75 gram (G) glucose tolerance test. Participants ingested 75 grams of glucose in 300-400 milliliters (mL) of water over 5 minutes. Blood samples were taken before ingesting glucose and then every 30 minutes for 120 minutes. Insulin sensitivity index was calculated by Matsuda and Defronzo's formula using the values obtained. A positive change from Baseline (increase in insulin sensitivity) indicates improvement.
Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) [ Time Frame: Baseline and Week 6 (Prior to ingesting glucose and every 30 minutes for 120 minutes) ]
Insulin resistance was measured using the 75 G glucose tolerance test. Participants ingested 75 grams of glucose in 300-400 mL of water over 5 minutes. Blood samples were taken before ingesting glucose and then every 30 minutes for 120 minutes. HOMA-IR was calculated using the Insulin and glucose levels obtained. A negative change (decrease in insulin resistance) indicates improvement.


Enrollment:	38
Study Start Date:	February 2009
Study Completion Date:	December 2013
Primary Completion Date:	August 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Spironolactone	Drug: Spironolactone 50 mg once daily for 6 weeks.
Placebo Comparator: Placebo	Drug: Placebo Placebo-matching spironolactone once daily for 6 weeks.

Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years to 70 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age 18-70 years
Good health as evidenced by history and physical exam
Body Mass Index (BMI): >30 kg/m2 and <45 kg/m2

Exclusion criteria:

Medical illnesses other than treated hypothyroidism
Blood Pressure (BP) >135/85 or systolic BP <90 mm Hg
Hepatic disease (transaminase > 3 times normal)
Renal impairment (Creatinine clearance <60 ml/min)
Baseline serum Potassium (K) >5.0 mmol/L
History of drug or alcohol abuse
Allergies to spironolactone
Participation in any other concurrent clinical trial
Women using oral contraceptives within the last 3 months

Contacts and Locations

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): NCT01406015

Locations


United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115

Sponsors and Collaborators

Brigham and Women's Hospital

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Brown JM, Williams JS, Luther JM, Garg R, Garza AE, Pojoga LH, Ruan DT, Williams GH, Adler GK, Vaidya A. Human interventions to characterize novel relationships between the renin-angiotensin-aldosterone system and parathyroid hormone. Hypertension. 2014 Feb;63(2):273-80. doi: 10.1161/HYPERTENSIONAHA.113.01910. Epub 2013 Nov 4.

Garg R, Kneen L, Williams GH, Adler GK. Effect of mineralocorticoid receptor antagonist on insulin resistance and endothelial function in obese subjects. Diabetes Obes Metab. 2014 Mar;16(3):268-72. doi: 10.1111/dom.12224. Epub 2013 Oct 31.


Responsible Party:	Rajesh K. Garg, Associate Physician, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:	NCT01406015 History of Changes
Other Study ID Numbers:	2009P-000311
First Submitted:	July 26, 2011
First Posted:	July 29, 2011
Results First Submitted:	January 29, 2017
Results First Posted:	April 28, 2017
Last Update Posted:	April 28, 2017
Last Verified:	March 2017

Keywords provided by Rajesh K. Garg, Brigham and Women's Hospital:


Obesity Insulin resistance Mineralocorticoid receptor

Additional relevant MeSH terms:


Obesity Insulin Resistance Overnutrition Nutrition Disorders Overweight Body Weight Signs and Symptoms Hyperinsulinism Glucose Metabolism Disorders Metabolic Diseases	Spironolactone Mineralocorticoids Mineralocorticoid Receptor Antagonists Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Diuretics, Potassium Sparing Diuretics Natriuretic Agents Hormones

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