Back to resultsMineralocorticoid Receptor and Obesity Induced Cardiovascular Complications
Primary Purpose
Obesity, Insulin Resistance
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Spironolactone
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Obesity focused on measuring Obesity, Insulin resistance, Mineralocorticoid receptor
Eligibility 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
Sites / Locations
- Brigham and Women's Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Spironolactone
Placebo
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
Full Information
NCT ID
NCT01406015
First Posted
July 26, 2011
Last Updated
March 20, 2017
Sponsor
Brigham and Women's Hospital
1. Study Identification
Unique Protocol Identification Number
NCT01406015
Brief Title
Mineralocorticoid Receptor and Obesity Induced Cardiovascular Complications
Official Title
Mineralocorticoid Receptor and Obesity Induced Cardiovascular Complications
Study Type
Interventional
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
February 2009 (undefined)
Primary Completion Date
August 2013 (Actual)
Study Completion Date
December 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brigham and Women's Hospital
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity, Insulin Resistance
Keywords
Obesity, Insulin resistance, Mineralocorticoid receptor
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
38 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Spironolactone
Arm Type
Active Comparator
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Spironolactone
Intervention Description
50 mg once daily for 6 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo-matching spironolactone once daily for 6 weeks.
Primary Outcome Measure Information:
Title
Change From Baseline in Post-ischemic Dilatation
Description
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.
Time Frame
Baseline and Week 6
Secondary Outcome Measure Information:
Title
Change From Baseline in Para-aminohippurate (PAH) Clearance
Description
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.
Time Frame
Baseline and Week 6 (Prior to PAH infusion and at 50 and 60 minutes post PAH infusion)
Title
Change From Baseline in Markers of Inflammation
Description
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.
Time Frame
Baseline and Week 6
Title
Change From Baseline in Insulin Sensitivity Index (ISI)
Description
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.
Time Frame
Baseline and Week 6 (Prior to ingesting glucose and every 30 minutes for 120 minutes)
Title
Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)
Description
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.
Time Frame
Baseline and Week 6 (Prior to ingesting glucose and every 30 minutes for 120 minutes)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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
Facility Information:
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
24191286
Citation
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.
Results Reference
derived
PubMed Identifier
24125483
Citation
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.
Results Reference
derived
Learn more about this trial
Mineralocorticoid Receptor and Obesity Induced Cardiovascular Complications
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