"Pecos" B-adrenergic and PPAR-G Stimulation Upregulates Lipid Metabolism in Human Subcutaneous Fat

Sponsor

Pennington Biomedical Research Center (Other)

Overall Status

Completed

CT.gov ID

NCT00377975

Collaborator

(none)

Enrollment

Location

Duration (Months)

4.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study compares four treatments to see which one causes the most weight loss, fat loss, loss of abdominal fat and improvement in blood tests like cholesterol. The four treatments are: Placebo, Ephedrine plus caffeine, Pioglitazone, Combined pioglitazone and ephedrine plus caffeine

Condition or Disease	Intervention/Treatment	Phase
Obesity	Drug: Ephedrine Drug: Pioglitazone Drug: Caffeine	Phase 2

Detailed Description

The sympathetic nervous system, via the intracellular messenger cAMP and MAPK activation, and thiazolidinediones via PPARγ control lipid metabolism have been implicated in body weight regulation. The present study was undertaken to determine whether the simultaneous activation of these two signaling systems might synergize to exert beneficial effects on the expression of key genes involved in lipid metabolism and mitochondrial biogenesis in subcutaneous fat in healthy, non-diabetic subjects. Fifty seven non-diabetic women and men were randomized into four groups: 1) placebo/placebo (PP); 2) ephedrine plus caffeine/placebo (ECP); 3) placebo/pioglitazone (PPio); 4) ephedrine plus caffeine/pioglitazone (ECPio). Adipose tissue samples were obtained after 12 weeks of treatment to determine gene expression by real time RT-PCR.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double

Primary Purpose:

Treatment

Official Title:

Synergistic Induction of UCP-1 by Ephedrine/Caffeine and Pioglitazone: A Rationale for Combination Therapy of Obesity

Study Start Date :

Jan 1, 2003

Study Completion Date :

Nov 1, 2004

Outcome Measures

Primary Outcome Measures

Percent fat after 16 weeks treatment using a Hologic QDR 4500 DEXA. []

Secondary Outcome Measures

UCP-1 gene expression by quantitative RT-PCR []
fat mass, lean mass []
visceral adiposity by multi-slice CT scanning []
resting metabolic rate and thermic effect of a single dose of ephedrine and caffeine []
adipose tissue gene expression profiling using oligonucleotide array []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

generally healthy
not pregnant or nursing
using adequate contraception
between 18 and 50 years of age
BMI between 30 and 35 kg/m2

Exclusion Criteria:

significant renal, cardiac, liver, lung or neurological disease
high blood pressure
diabetes
prior use of thiazolidinedione
prior use of beta-blockers alcohol or drug abuse
history of thrombophlebitis, vascular or blood clotting disorders
unwilling or unable to abstain from caffeinated beverages and alcohol prior to adipose tissue biopsy and metabolic rates measurements
increased liver function test at baseline
have metal objects that would interfere with the measurement of the body composition
use drugs known to affect lipid metabolism, energy metabolism or body weight
use herbal supplements containing ephedrine and/or caffeine
take chronic medication, except hormone replacement or contraception
are a woman unwilling to use effective contraception during the trial
have heart disease or history of stroke
have urinary symptoms from enlarged prostate
have gained and or lost more than 10 pounds in the last 6 month
have use a monoamine oxidase inhibitor medication in the last month
have high or low thyroid function that has not been controlled in the normal range for at least 2 months