Trial Outcomes & Findings for Study of TNF-Antagonism in the Metabolic Syndrome (II) (NCT NCT00413400)

NCT ID: NCT00413400

Last Updated: 2010-12-02

Results Overview

As a measure of C-reactive protein (CRP), which is an inflammatory marker, Log10 of the CRP at 6 months is reported

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 40 participants
• Primary outcome timeframe: 6 months
• Results posted on: 2010-12-02

Participant Flow

Recruitment period 12/2006 to 3/2009

Participant milestones

Measure	Placebo Placebo injections, subcutaneously, twice weekly x 3 months, then once weekly x 3 months	Etanercept Etanercept 50mg subcutaneously twice weekly x 3 months, then once weekly x 3 months
Overall Study STARTED	24	16
Overall Study 3 Month Visit	22	12
Overall Study COMPLETED	22	12
Overall Study NOT COMPLETED	2	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of TNF-Antagonism in the Metabolic Syndrome (II)

Baseline characteristics by cohort

Measure	Placebo n=24 Participants Placebo injections, subcutaneously, twice weekly x 3 months, then once weekly x 3 months	Etanercept n=16 Participants Etanercept 50mg subcutaneously twice weekly x 3 months, then once weekly x 3 months	Total n=40 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	24 Participants n=5 Participants	16 Participants n=7 Participants	40 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	47 years STANDARD_DEVIATION 8 • n=5 Participants	41 years STANDARD_DEVIATION 9 • n=7 Participants	45 years STANDARD_DEVIATION 9 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	8 Participants n=7 Participants	20 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	8 Participants n=7 Participants	20 Participants n=5 Participants
Region of Enrollment United States	24 participants n=5 Participants	16 participants n=7 Participants	40 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

As a measure of C-reactive protein (CRP), which is an inflammatory marker, Log10 of the CRP at 6 months is reported

Outcome measures

Measure	Placebo n=22 Participants Placebo injections, subcutaneously, twice weekly x 3 months, then once weekly x 3 months	Etanercept n=12 Participants Etanercept 50mg subcutaneously twice weekly x 3 months, then once weekly x 3 months
C-reactive Protein (CRP)	0.61 Log10 mg/L Standard Error 0.06	0.68 Log10 mg/L Standard Error 0.18

PRIMARY outcome

Timeframe: 6 months

6 month value of IL-6 (pg/mL)

Outcome measures

Measure	Placebo n=22 Participants Placebo injections, subcutaneously, twice weekly x 3 months, then once weekly x 3 months	Etanercept n=12 Participants Etanercept 50mg subcutaneously twice weekly x 3 months, then once weekly x 3 months
Interleukin-6 (IL-6)	8.2 pg/mL Standard Error 1.1	11.3 pg/mL Standard Error 2.1

PRIMARY outcome

Timeframe: 6 months

The ratio of circulating high molecular weight (HMW) adiponectin to total adiponectin ratio (HMW:total Adiponectin) at 6 months is reported.

Outcome measures

Measure	Placebo n=22 Participants Placebo injections, subcutaneously, twice weekly x 3 months, then once weekly x 3 months	Etanercept n=12 Participants Etanercept 50mg subcutaneously twice weekly x 3 months, then once weekly x 3 months
Adiponectin	0.30 (ratio) Standard Error 0.08	0.40 (ratio) Standard Error 0.15

SECONDARY outcome

Timeframe: 6 months

Fasting glucose (mg/dL) at 6mo

Outcome measures

Measure	Placebo n=22 Participants Placebo injections, subcutaneously, twice weekly x 3 months, then once weekly x 3 months	Etanercept n=12 Participants Etanercept 50mg subcutaneously twice weekly x 3 months, then once weekly x 3 months
Glucose Tolerance	95 mg/dL Standard Error 5	91 mg/dL Standard Error 6

SECONDARY outcome

Timeframe: 6 months

Reactive Hyperemia Index (RHI) using peripheral artery tonometry (using Endo-PAT 2000). Peripheral artery tonometry measures blood flow in the tip of the index finger at baseline and in response to vaso-occlusion (inflated blood pressure cuff). The reactive hyperemia index is an index of vasodilation after occlusion compared to baseline. A higher value indicates better vasoreactivity. As this is a relatively new test, there are no thoroughly validated clinically utilized norms.

Outcome measures

Measure	Placebo n=22 Participants Placebo injections, subcutaneously, twice weekly x 3 months, then once weekly x 3 months	Etanercept n=12 Participants Etanercept 50mg subcutaneously twice weekly x 3 months, then once weekly x 3 months
Endothelial Function	1.8 (index) Standard Error 0.11	2.0 (index) Standard Error 0.15

SECONDARY outcome

Timeframe: Baseline to 6 months

Change in WBC during study (WBC at six months minus WBC at baseline)

Outcome measures

Measure	Placebo n=22 Participants Placebo injections, subcutaneously, twice weekly x 3 months, then once weekly x 3 months	Etanercept n=12 Participants Etanercept 50mg subcutaneously twice weekly x 3 months, then once weekly x 3 months
White Blood Cell (WBC) Count	-0.17 th/cumm Standard Error 0.23	-0.04 th/cumm Standard Error 0.45

SECONDARY outcome

Timeframe: Baseline to 6 months

change in EF (6mo - baseline). Please note that the value given is the absolute change in EF (which has units of percent), not the percent change in the variable.

Outcome measures

Measure	Placebo n=22 Participants Placebo injections, subcutaneously, twice weekly x 3 months, then once weekly x 3 months	Etanercept n=12 Participants Etanercept 50mg subcutaneously twice weekly x 3 months, then once weekly x 3 months
Cardiac Echo Ejection Fraction (EF)	1.1 percent Standard Error 0.7	-1.1 percent Standard Error 1.2

SECONDARY outcome

Timeframe: 6 months

6 month visceral adipose tissue (cm^2) - cross-sectional area of the visceral adipose tissue at the level of the 4th lumbar vertebrae was measured using single-slice abdominal computed tomography (CT) scan

Outcome measures

Measure	Placebo n=22 Participants Placebo injections, subcutaneously, twice weekly x 3 months, then once weekly x 3 months	Etanercept n=12 Participants Etanercept 50mg subcutaneously twice weekly x 3 months, then once weekly x 3 months
Body Composition	206 cm^2 Standard Error 18	186 cm^2 Standard Error 14

SECONDARY outcome

Timeframe: 6 months

Circulating concentrations of Tumor necrosis factor receptor 2 (TNFR2) at 6 months

Outcome measures

Measure	Placebo n=22 Participants Placebo injections, subcutaneously, twice weekly x 3 months, then once weekly x 3 months	Etanercept n=12 Participants Etanercept 50mg subcutaneously twice weekly x 3 months, then once weekly x 3 months
Tumor Necrosis Factor (TNF) Receptor	2573 pg/mL Standard Error 148	4518 pg/mL Standard Error 329

SECONDARY outcome

Timeframe: 6 months

circulating resistin at 6 months

Outcome measures

Measure	Placebo n=22 Participants Placebo injections, subcutaneously, twice weekly x 3 months, then once weekly x 3 months	Etanercept n=12 Participants Etanercept 50mg subcutaneously twice weekly x 3 months, then once weekly x 3 months
Other Adipocytokines	6.7 ng/mL Standard Error 0.5	8.6 ng/mL Standard Error 1.1

SECONDARY outcome

Timeframe: 6 months

total cholesterol (mg/dL) at 6 months

Outcome measures

Measure	Placebo n=22 Participants Placebo injections, subcutaneously, twice weekly x 3 months, then once weekly x 3 months	Etanercept n=12 Participants Etanercept 50mg subcutaneously twice weekly x 3 months, then once weekly x 3 months
Lipid Levels	196 mg/dL Standard Error 9	201 mg/dL Standard Error 12

SECONDARY outcome

Timeframe: 6 months

fold-change in subcutaneous adipose tissue expression of TNF-alpha (mRNA) after 6 months

Outcome measures

Measure	Placebo n=8 Participants Placebo injections, subcutaneously, twice weekly x 3 months, then once weekly x 3 months	Etanercept n=4 Participants Etanercept 50mg subcutaneously twice weekly x 3 months, then once weekly x 3 months
Adipocyte Messenger Ribonucleic Acid (mRNA) Levels of Adipocytokines Including Tumor Necrosis Factor (TNF) -Alpha	2.3 fold-change Standard Error 0.7	1.1 fold-change Standard Error 0.3

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 8 other events

Deaths: 0 deaths

Etanercept

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=24 participants at risk Placebo injections, subcutaneously, twice weekly x 3 months, then once weekly x 3 months	Etanercept n=16 participants at risk Etanercept 50mg subcutaneously twice weekly x 3 months, then once weekly x 3 months
Musculoskeletal and connective tissue disorders Operative Surgical Procedure	4.2% 1/24 • Number of events 1 • 6 months	6.2% 1/16 • Number of events 1 • 6 months
Nervous system disorders Paresthesia	0.00% 0/24 • 6 months	6.2% 1/16 • Number of events 1 • 6 months
Psychiatric disorders Schizophrenia	4.2% 1/24 • Number of events 1 • 6 months	0.00% 0/16 • 6 months

Other adverse events

Measure	Placebo n=24 participants at risk Placebo injections, subcutaneously, twice weekly x 3 months, then once weekly x 3 months	Etanercept n=16 participants at risk Etanercept 50mg subcutaneously twice weekly x 3 months, then once weekly x 3 months
Musculoskeletal and connective tissue disorders Bakers Cyst	4.2% 1/24 • Number of events 1 • 6 months	6.2% 1/16 • Number of events 1 • 6 months
Infections and infestations Dental Infection	4.2% 1/24 • Number of events 2 • 6 months	0.00% 0/16 • 6 months
Gastrointestinal disorders Diarrhea	4.2% 1/24 • Number of events 1 • 6 months	6.2% 1/16 • Number of events 1 • 6 months
General disorders Foot Swelling	4.2% 1/24 • Number of events 1 • 6 months	0.00% 0/16 • 6 months
Infections and infestations Influenza	4.2% 1/24 • Number of events 1 • 6 months	0.00% 0/16 • 6 months
Musculoskeletal and connective tissue disorders Joint Pain	4.2% 1/24 • Number of events 1 • 6 months	0.00% 0/16 • 6 months
Blood and lymphatic system disorders Leukocytopenia	0.00% 0/24 • 6 months	6.2% 1/16 • Number of events 1 • 6 months
Nervous system disorders Paresthesia	0.00% 0/24 • 6 months	6.2% 1/16 • Number of events 1 • 6 months
Skin and subcutaneous tissue disorders Rash	4.2% 1/24 • Number of events 1 • 6 months	0.00% 0/16 • 6 months
Infections and infestations Upper respiratory infection	4.2% 1/24 • Number of events 1 • 6 months	12.5% 2/16 • Number of events 3 • 6 months

Additional Information

Steven K. Grinspoon

Massachusetts General Hospital

Phone: 617-724-9109

Email: sgrinspoon@partners.org

Results disclosure agreements

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