Trial Outcomes & Findings for Angiotensin II Blockade and Inflammation in Obesity (NCT NCT01684748)

Last Updated: 2018-01-03

Results Overview

Data collected from the intravenous glucose tolerance tests included blood concentrations of glucose and insulin. Glucose was measured immediately on a YSI glucose analyzer and insulin was measured via ELISA colormetric kits once all study samples were collected. To analyze changes in insulin sensitivity, the MINMOD software was used. The MINMOD software uses Bergman's minimal model to determine insulin sensitivity during an intravenous glucose tolerance test. Both glucose and insulin values were inserted at each timepoint collected (33 in total over the 3-hour protocol) and the software was run to generate the insulin sensitivity value at baseline and post-test. This information was then used to calculate the change of insulin sensitivity from baseline to post-testing after each 8-week intervention.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

20 participants

Primary outcome timeframe

Baseline testing to post-testing after 8-week intervention

Results posted on

2018-01-03

Participant Flow

Participant milestones

Participant milestones
Measure	Olmesartan Medoxomil First, Then No Drug During the First Intervention (8 weeks), subjects will be provided with daily 20 mg of olmesartan for the first 2 weeks. Subjects receive additional daily doses of 40 mg olmesartan for the remainder of the study period (6 weeks). The dose remains at 20 mg per day, however, if BP falls below 110/70 during the first 2 weeks. In addition, subjects will continue taking the drug during the 2-week follow-up testing period. Subjects will then proceed to the Washout period (2 weeks). During the Second Intervention (8 weeks), no drug will be administered to the subjects. Olmesartan medoxomil	No Drug First, Then Olmesartan Medoxomil During the First Intervention (8 weeks), no drug will be administered to the subjects. Subjects will then proceed to the Washout period (2 weeks). During the Second Intervention (8 weeks), subjects will be provided with daily 20 mg of olmesartan for the first 2 weeks. Subjects then receive daily doses of 40 mg olmesartan for the remainder of the study period (6 weeks). The dose remains at 20 mg per day, however, if BP falls below 110/70 during the first 2 weeks. In addition, subjects will continue taking the drug during the 2-week follow-up testing period.
First Intervention - 8 Weeks STARTED	10	10
First Intervention - 8 Weeks COMPLETED	8	8
First Intervention - 8 Weeks NOT COMPLETED	2	2
Second Intervention - 8 Weeks STARTED	8	8
Second Intervention - 8 Weeks COMPLETED	8	8
Second Intervention - 8 Weeks NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Angiotensin II Blockade and Inflammation in Obesity

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Olmesartan Medoxomil First, Then No Drug n=8 Participants During the First Intervention (8 weeks), subjects will be provided with daily 20 mg of olmesartan for the first 2 weeks. Subjects receive additional daily doses of 40 mg olmesartan for the remainder of the study period (6 weeks). The dose remains at 20 mg per day, however, if BP falls below 110/70 during the first 2 weeks. In addition, subjects will continue taking the drug during the 2-week follow-up testing period. Subjects will then proceed to the Washout period (2 weeks). During the Second Intervention (8 weeks), no drug will be administered to the subjects. Olmesartan medoxomil	No Drug First, Then Olmesartan Medoxomil n=8 Participants During the First Intervention (8 weeks), no drug will be administered to the subjects. Subjects will then proceed to the Washout period (2 weeks). During the Second Intervention (8 weeks), subjects will be provided with daily 20 mg of olmesartan for the first 2 weeks. Subjects then receive daily doses of 40 mg olmesartan for the remainder of the study period (6 weeks). The dose remains at 20 mg per day, however, if BP falls below 110/70 during the first 2 weeks. In addition, subjects will continue taking the drug during the 2-week follow-up testing period.	Total n=16 Participants Total of all reporting groups
Age, Continuous	49.25 years STANDARD_DEVIATION 9.8 • n=5 Participants	49.75 years STANDARD_DEVIATION 14.2 • n=7 Participants	49.5 years STANDARD_DEVIATION 11.8 • n=5 Participants
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	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Region of Enrollment United States	8 participants n=5 Participants	8 participants n=7 Participants	16 participants n=5 Participants
Body weight	102.3 kg STANDARD_DEVIATION 20.9 • n=5 Participants	90.4 kg STANDARD_DEVIATION 17.7 • n=7 Participants	96.3 kg STANDARD_DEVIATION 19.7 • n=5 Participants
Body mass index	34.5 kg/m2 STANDARD_DEVIATION 7.0 • n=5 Participants	31.5 kg/m2 STANDARD_DEVIATION 6.8 • n=7 Participants	33.0 kg/m2 STANDARD_DEVIATION 6.9 • n=5 Participants
Body fat	43.9 Percentage of fat STANDARD_DEVIATION 10.5 • n=5 Participants	39.8 Percentage of fat STANDARD_DEVIATION 13.5 • n=7 Participants	41.8 Percentage of fat STANDARD_DEVIATION 12.1 • n=5 Participants
Total fat mass	43.1 kg STANDARD_DEVIATION 15.1 • n=5 Participants	34.6 kg STANDARD_DEVIATION 14.7 • n=7 Participants	38.8 kg STANDARD_DEVIATION 15.0 • n=5 Participants
Systolic blood pressure	133.7 mmHg STANDARD_DEVIATION 10.1 • n=5 Participants	140.6 mmHg STANDARD_DEVIATION 12.8 • n=7 Participants	137.2 mmHg STANDARD_DEVIATION 11.7 • n=5 Participants
Diastolic blood pressure	81.0 mmHg STANDARD_DEVIATION 5.1 • n=5 Participants	80.1 mmHg STANDARD_DEVIATION 7.9 • n=7 Participants	80.6 mmHg STANDARD_DEVIATION 6.4 • n=5 Participants
Triglycerides	120.6 mg/dL STANDARD_DEVIATION 68.5 • n=5 Participants	106.8 mg/dL STANDARD_DEVIATION 50.9 • n=7 Participants	113.7 mg/dL STANDARD_DEVIATION 53.6 • n=5 Participants
Total cholesterol	199.5 mg/dL STANDARD_DEVIATION 38.2 • n=5 Participants	207.8 mg/dL STANDARD_DEVIATION 20.9 • n=7 Participants	203.7 mg/dL STANDARD_DEVIATION 30.1 • n=5 Participants
HDL cholesterol	45.5 mg/dL STANDARD_DEVIATION 9.8 • n=5 Participants	55.1 mg/dL STANDARD_DEVIATION 29.0 • n=7 Participants	50.3 mg/dL STANDARD_DEVIATION 21.5 • n=5 Participants
LDL cholesterol	129.9 mg/dL STANDARD_DEVIATION 34.9 • n=5 Participants	131.3 mg/dL STANDARD_DEVIATION 22.4 • n=7 Participants	130.6 mg/dL STANDARD_DEVIATION 31.2 • n=5 Participants
Glucose	95.8 mg/dL STANDARD_DEVIATION 10.8 • n=5 Participants	99.1 mg/dL STANDARD_DEVIATION 13.8 • n=7 Participants	97.4 mg/dL STANDARD_DEVIATION 12.0 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline testing to post-testing after 8-week intervention

Population: Results of insulin sensitivity by intravenous glucose tolerance (IVGTT) testing are reported per intervention (Olmesartan Medoxomil and No drug). Only 10 of the 16 study participants who participated in all or some of the study measurements opted to complete or had sufficient data to analyze for each pre- and post-intervention (4 total) IVGTT.

Outcome measures

Outcome measures
Measure	Olmesartan Medoxomil n=10 Participants Subjects will be provided with daily 20 mg of olmesartan for the first 2 weeks during the 8-week intervention. Subjects receive additional daily doses of 40 mg olmesartan for the remainder of the study period. The dose remains at 20 mg per day, however, if BP falls below 110/70 during the first 2 weeks, subjects will continue taking the drug during the 2-week follow-up period. Olmesartan medoxomil	No Drug Intervention n=10 Participants The no-drug intervention (i.e., no placebo is provided) is an 8-week no intervention comparison.
Insulin Sensitivity by Intravenous Glucose Tolerance Testing (Change Over Time)	0.253 mu/L/min Standard Deviation 2.7	-0.804 mu/L/min Standard Deviation 2.2

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline testing to post-testing after 8-week intervention

Population: Results are reported for the Olmesartan Medoxomil intervention only; there was insufficient RNA yield for the majority of participants during the no drug treatment. Only 7 of the 16 study participants who participated in the study measurements had sufficient data to analyze the pre- and post-intervention skeletal muscle biopsy tissues.

RNA extraction and quantification were determined using an RNeasy Mini Fibrous Kit and DNase I treatment (Qiagen, Valencia, CA, USA) in accordance to the manufacturer's directions for mRNA extraction. Quantitative real-time polymerase chain reaction (qRT-PCR) measured the expression of collagen III using an ABI PRISM 7900 Sequence Detection System instrument and TaqMan Universal PCR Master Mix according to the manufacturer's instructions (Applied Biosystems, Foster City, CA, USA). Relative gene expression levels were determined using the number of cycles necessary to reach threshold and results were normalized to cyclophilin B RNA levels.

Outcome measures

Outcome measures
Measure	Olmesartan Medoxomil n=7 Participants Subjects will be provided with daily 20 mg of olmesartan for the first 2 weeks during the 8-week intervention. Subjects receive additional daily doses of 40 mg olmesartan for the remainder of the study period. The dose remains at 20 mg per day, however, if BP falls below 110/70 during the first 2 weeks, subjects will continue taking the drug during the 2-week follow-up period. Olmesartan medoxomil	No Drug Intervention The no-drug intervention (i.e., no placebo is provided) is an 8-week no intervention comparison.
Collagen Gene Expression in Skeletal Muscle (Change Over Time) Pre-Olmesartan medoxomil	1491 Arbitrary unit (AU) Standard Error 510	—
Collagen Gene Expression in Skeletal Muscle (Change Over Time) Post-Olmesartan medoxomil	774 Arbitrary unit (AU) Standard Error 271	—

Adverse Events

Olmesartan Medoxomil

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

No Drug Intervention

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

Elaina Marinik, Ph.D.

Virginia Polytechnic Institute & State University

Phone: 5402318299

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place