Mineralocorticoid Receptor and Obesity Induced Cardiovascular Complications

Study Overview
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Brief Summary
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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.

Official Title
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Mineralocorticoid Receptor and Obesity Induced Cardiovascular Complications

Conditions
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Obesity, Insulin Resistance

Intervention / Treatment
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* Drug: Spironolactone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Spironolactone<br> | Drug: Spironolactone<br>* 50 mg once daily for 6 weeks.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo-matching spironolactone once daily for 6 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Post-ischemic Dilatation | 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. | Baseline and Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Para-aminohippurate (PAH) Clearance | 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. | Baseline and Week 6 (Prior to PAH infusion and at 50 and 60 minutes post PAH infusion) | 
| Change From Baseline in Markers of Inflammation | 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. | Baseline and Week 6 | 
| Change From Baseline in Insulin Sensitivity Index (ISI) | 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. | Baseline and Week 6 (Prior to ingesting glucose and every 30 minutes for 120 minutes) | 
| Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) | 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. | Baseline and Week 6 (Prior to ingesting glucose and every 30 minutes for 120 minutes) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Insulin resistance, Mineralocorticoid receptor