Trial Outcomes & Findings for A Randomized Clinical Trial To Study Losartan On Endothelial Dysfunction and Insulin Resistance In Obese Patients (NCT NCT00675987)

NCT ID: NCT00675987

Last Updated: 2018-09-06

Results Overview

Insulin clamp derived insulin sensitivity, as insulin stimulated glucose disposal corrected for steady state insulin level.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 53 participants
• Primary outcome timeframe: baseline, 8 weeks
• Results posted on: 2018-09-06

Participant Flow

Participant milestones

Measure	Losartan 100 mg 1 Tab po QD Losartan 100 mg 1 tab po QD	Placebo 1 Tab po QD Placebo 1 tab po QD
Overall Study STARTED	26	27
Overall Study COMPLETED	26	27
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Randomized Clinical Trial To Study Losartan On Endothelial Dysfunction and Insulin Resistance In Obese Patients

Baseline characteristics by cohort

Measure	Losartan 100 mg 1 Tab po QD n=26 Participants Losartan 100 mg 1 tab po QD	Placebo 1 Tab po QD n=27 Participants Placebo 1 tab po QD	Total n=53 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	26 Participants n=5 Participants	27 Participants n=7 Participants	53 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	51.1 years STANDARD_DEVIATION 10.5 • n=5 Participants	53.8 years STANDARD_DEVIATION 8.3 • n=7 Participants	52.5 years STANDARD_DEVIATION 9.5 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	12 Participants n=7 Participants	26 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	15 Participants n=7 Participants	27 Participants n=5 Participants
Region of Enrollment United States	26 participants n=5 Participants	27 participants n=7 Participants	53 participants n=5 Participants

PRIMARY outcome

Timeframe: baseline, 8 weeks

Population: analysis was ITT, but limited to those with interpretable data (3 clamp studies were excluded)

Insulin clamp derived insulin sensitivity, as insulin stimulated glucose disposal corrected for steady state insulin level.

Outcome measures

Measure	Placebo n=27 Participants Placebo 1 tab po QD	Losartan n=26 Participants Losartan 100 mg 1 tab po QD
Insulin Sensitivity Utilizing the Euglycemic Hyperinsulinemic Clamp	5.3 mg/kg/min Standard Deviation 4.5	2.8 mg/kg/min Standard Deviation 1.7

PRIMARY outcome

Timeframe: baseline, 8 weeks

Population: analysis was ITT, but limited to those with interpretable data (3 clamp studies were excluded)

Endothelial function assessed as the ratio of pulse volume amplitude after compared with before a reactive hyperemia stimulus, measured by peripheral (fingertip) arterial tonometry. Reported values indicate the percentage change from Baseline in the ratio of pulse volume amplitude after compared to before the reactive hyperemia stimulus.

Outcome measures

Measure	Placebo n=27 Participants Placebo 1 tab po QD	Losartan n=26 Participants Losartan 100 mg 1 tab po QD
Insulin Sensitivity Utilizing Endothelial Function as Assessed by Pulse Volume Amplitude	1.76 percentage change Standard Deviation 0.7	2.11 percentage change Standard Deviation 0.7

SECONDARY outcome

Timeframe: baseline, 8 weeks

Population: 27 participants were randomized to placebo, and 26 participants were randomized to Losartan, but 1 placebo participant and 1 Losartan participant did not complete the study.

Urine was obtained to assess for the presence of microalbuminuria.

Outcome measures

Measure	Placebo n=26 Participants Placebo 1 tab po QD	Losartan n=25 Participants Losartan 100 mg 1 tab po QD
Change in Urine Albumin/Creatine	0.4 mg/mmol Interval -0.1 to 0.9	0.2 mg/mmol Interval -0.3 to 0.8

SECONDARY outcome

Timeframe: baseline, 8 weeks

Population: 27 participants were randomized to placebo, and 26 participants were randomized to Losartan, but 1 placebo participant and 1 Losartan participant did not complete the study.

hsCRP (high-sensitivity C-reactive protein) is a marker of inflammation

Outcome measures

Measure	Placebo n=26 Participants Placebo 1 tab po QD	Losartan n=25 Participants Losartan 100 mg 1 tab po QD
Change in hsCRP (High-sensitivity C-reactive Protein)	-10 percentage change Interval -32.0 to 20.0	-34 percentage change Interval -50.0 to -13.0

SECONDARY outcome

Timeframe: baseline, 8 weeks

Population: 27 participants were randomized to placebo, and 26 participants were randomized to Losartan, but 1 placebo participant and 1 Losartan participant did not complete the study.

VCAM-1 is an immunoglobulin-like adhesion molecule expressed on activated endothelial cells.

Outcome measures

Measure	Placebo n=26 Participants Placebo 1 tab po QD	Losartan n=25 Participants Losartan 100 mg 1 tab po QD
Change in VCAM-1(Vascular Cell-adhesion Molecule-1)	29 ng/ml Interval -20.0 to 79.0	-21 ng/ml Interval -70.0 to 28.0

SECONDARY outcome

Timeframe: baseline, 8 weeks

Population: 27 participants were randomized to placebo, and 26 participants were randomized to Losartan, but 1 placebo participant and 1 Losartan participant did not complete the study.

MCP-1 is one of the key chemokines that regulate migration and infiltration of monocytes/macrophages.

Outcome measures

Measure	Placebo n=26 Participants Placebo 1 tab po QD	Losartan n=25 Participants Losartan 100 mg 1 tab po QD
Change in MCP-1 (Monocyte Chemoattractant Protein-1)	-37 pg/ml Interval -80.0 to 6.8	-24 pg/ml Interval -65.0 to 18.0

SECONDARY outcome

Timeframe: baseline, 8 weeks

Population: 27 participants were randomized to placebo, and 26 participants were randomized to Losartan, but 1 placebo participant and 1 Losartan participant did not complete the study.

ox-LDL measures protein damage due to the oxidative modification of the ApoB subunit on LDL cholesterol.

Outcome measures

Measure	Placebo n=26 Participants Placebo 1 tab po QD	Losartan n=25 Participants Losartan 100 mg 1 tab po QD
Change in Ox-LDL (Oxidized Low-density Lipoprotein)	-2.0 units/l Interval -8.1 to 4.1	-5.5 units/l Interval -11.9 to 0.9

SECONDARY outcome

Timeframe: baseline, 8 weeks

Population: 27 participants were randomized to placebo, and 26 participants were randomized to Losartan, but 1 placebo participant and 1 Losartan participant did not complete the study.

F2-isoprostanes is a marker of oxidative stress.

Outcome measures

Measure	Placebo n=26 Participants Placebo 1 tab po QD	Losartan n=25 Participants Losartan 100 mg 1 tab po QD
Change in F2-isoprostanes	0.4 ng/mg of creatinine Interval -0.9 to 1.6	0.9 ng/mg of creatinine Interval -0.4 to 2.2

SECONDARY outcome

Timeframe: baseline, 8 weeks

Population: 27 participants were randomized to placebo, and 26 participants were randomized to Losartan, but 1 placebo participant and 1 Losartan participant did not complete the study.

E-selectin is expressed on inflamed endothelial cells in response to treatment with inflammatory cytokines.

Outcome measures

Measure	Placebo n=26 Participants Placebo 1 tab po QD	Losartan n=25 Participants Losartan 100 mg 1 tab po QD
Change in E-selectin	-1.6 ng/ml Interval -4.5 to 1.3	-0.6 ng/ml Interval -3.5 to 2.3

Adverse Events

Losartan

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

Mark A. Creager, MD

Brigham and Women's Hospital

Phone: 617-732-5267

Email: mcreager@partners.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place