Trial Outcomes & Findings for Mineralocorticoid Receptor and Obesity Induced Cardiovascular Complications (NCT NCT01406015)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

38 participants

Primary outcome timeframe

Baseline and Week 6

Results posted on

2017-04-28

Participant Flow

Participant milestones

Participant milestones
Measure	Spironolactone Spironolactone 50 mg once daily for 6 weeks.	Placebo Placebo-matching spironolactone once daily for 6 weeks.
Overall Study STARTED	19	19
Overall Study COMPLETED	16	16
Overall Study NOT COMPLETED	3	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Spironolactone Spironolactone 50 mg once daily for 6 weeks.	Placebo Placebo-matching spironolactone once daily for 6 weeks.
Overall Study Withdrawal by Subject	3	3

Baseline Characteristics

Mineralocorticoid Receptor and Obesity Induced Cardiovascular Complications

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Spironolactone n=16 Participants Spironolactone 50 mg once daily for 6 weeks.	Placebo n=16 Participants Placebo-matching spironolactone once daily for 6 weeks.	Total n=32 Participants Total of all reporting groups
Age, Continuous	47 years STANDARD_DEVIATION 11.6 • n=5 Participants	40 years STANDARD_DEVIATION 12.3 • n=7 Participants	43.4 years STANDARD_DEVIATION 12.3 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	12 Participants n=7 Participants	22 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Body Mass Index (BMI)	38 kg/m^2 STANDARD_DEVIATION 6.6 • n=5 Participants	36 kg/m^2 STANDARD_DEVIATION 4.6 • n=7 Participants	36.8 kg/m^2 STANDARD_DEVIATION 5.8 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 6

Population: All randomized participants who completed the study.

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.

Outcome measures

Outcome measures
Measure	Spironolactone n=16 Participants Spironolactone 50 mg once daily for 6 weeks.	Placebo n=16 Participants Placebo-matching spironolactone once daily for 6 weeks.
Change From Baseline in Post-ischemic Dilatation Baseline	9.6 percent dilalation Standard Deviation 7.8	10.2 percent dilalation Standard Deviation 6.9
Change From Baseline in Post-ischemic Dilatation Change from Baseline at Week 6	-1.2 percent dilalation Standard Deviation 6.1	-2.0 percent dilalation Standard Deviation 4.7

SECONDARY outcome

Timeframe: Baseline and Week 6 (Prior to PAH infusion and at 50 and 60 minutes post PAH infusion)

Population: All randomized participants who completed the study.

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.

Outcome measures

Outcome measures
Measure	Spironolactone n=16 Participants Spironolactone 50 mg once daily for 6 weeks.	Placebo n=16 Participants Placebo-matching spironolactone once daily for 6 weeks.
Change From Baseline in Para-aminohippurate (PAH) Clearance Baseline	488 mL/min Standard Deviation 80	521 mL/min Standard Deviation 116
Change From Baseline in Para-aminohippurate (PAH) Clearance Change from Baseline at Week 6	-2.3 mL/min Standard Deviation 28.7	-5.2 mL/min Standard Deviation 25.3

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Analysis was not performed.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Week 6 (Prior to ingesting glucose and every 30 minutes for 120 minutes)

Population: All randomized participants who completed the study.

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.

Outcome measures

Outcome measures
Measure	Spironolactone n=16 Participants Spironolactone 50 mg once daily for 6 weeks.	Placebo n=16 Participants Placebo-matching spironolactone once daily for 6 weeks.
Change From Baseline in Insulin Sensitivity Index (ISI) Baseline	3.7 IS index Standard Deviation 1.4	4.6 IS index Standard Deviation 3.7
Change From Baseline in Insulin Sensitivity Index (ISI) Change from Baseline at Week 6	-0.1 IS index Standard Deviation 0.8	-1.1 IS index Standard Deviation 2.7

SECONDARY outcome

Timeframe: Baseline and Week 6 (Prior to ingesting glucose and every 30 minutes for 120 minutes)

Population: All randomized participants who completed the study.

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.

Outcome measures

Outcome measures
Measure	Spironolactone n=16 Participants Spironolactone 50 mg once daily for 6 weeks.	Placebo n=16 Participants Placebo-matching spironolactone once daily for 6 weeks.
Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Baseline	2.7 IR index Standard Deviation 1.2	3.4 IR index Standard Deviation 3.2
Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Change from Baseline at Week 6	0.1 IR index Standard Deviation 1.1	0.1 IR index Standard Deviation 4.4

Adverse Events

Spironolactone

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Rajesh K. Garg

Brigham and Women's Hospital

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place