Mineralocorticoid Receptor and Obesity Induced Cardiovascular Complications

Not Applicable

Completed

• Conditions: Obesity; Insulin Resistance
• Interventions: Drug: Placebo; Drug: Spironolactone

• Registration Number: NCT01406015
• Lead Sponsor: Brigham and Women's Hospital

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-02
• Study First Submitted: 2011-07-26
• Study First Submitted QC: 2011-07-28
• Study First Posted: 2011-07-29
• Primary Completion: 2013-08
• Study Completion: 2013-12
• Results First Submitted: 2017-01-29
• Status Verified: 2017-03
• Results First Submitted QC: 2017-03-20
• Last Update Submitted: 2017-03-20
• Results First Posted: 2017-04-28
• Last Update Posted: 2017-04-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 38

Inclusion Criteria

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

Exclusion criteria:

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Spironolactone	Spironolactone	-

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Post-ischemic Dilatation	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

Name	Time	Method
Change From Baseline in Para-aminohippurate (PAH) Clearance	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	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 Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)	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.
Change From Baseline in Insulin Sensitivity Index (ISI)	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.

Trial Locations

Locations (1)

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States