Clinical trial NCT00377975: "Pecos" B-adrenergic and PPAR-G Stimulation Upregulates Lipid Metabolism in Human Subcutaneous Fat
Official title: Synergistic Induction of UCP-1 by Ephedrine/Caffeine and Pioglitazone: A Rationale for Combination Therapy of Obesity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Obesity
Keywords: UCP-1
ephedrine
caffeine
pioglitazone
Lead sponsor: Pennington Biomedical Research Center
Sponsor class: OTHER
First posted: 2006-09-19
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percent fat after 16 weeks treatment using a Hologic QDR 4500 DEXA.
Secondary outcomes:
measure: UCP-1 gene expression by quantitative RT-PCR
measure: fat mass, lean mass
measure: visceral adiposity by multi-slice CT scanning
measure: resting metabolic rate and thermic effect of a single dose of ephedrine and caffeine
measure: adipose tissue gene expression profiling using oligonucleotide array
Other outcomes:
Locations:
city: Baton Rouge
country: United States
facility: Pennington Biomedical Research Center
state: Louisiana
Study officials:
affiliation: Pennington Biomedical Research Center
name: Steven R Smith, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pasarica M, Xie H, Hymel D, Bray G, Greenway F, Ravussin E, Smith SR. Lower total adipocyte number but no evidence for small adipocyte depletion in patients with type 2 diabetes. Diabetes Care. 2009 May;32(5):900-2. doi: 10.2337/dc08-2240. Epub 2009 Feb 19.