Effect on Energy Metabolism at Cellular Level of Diet Plus Treatment With Ephedrine and Caffeine in Obesity

• Status: Completed
• Trial end date: 2007-11-01
• Target enrollment: 0
• Participant gender: Female

Summary

Brief Summary This trial was part of a sub-project targeted to diet, thermogenesis and obesity of a larger multicentre study named "Interaction between nutritional, social-behavioral and metabolic factors for prevention of cardiovascular disease: development of nutritional strategies on general population".

Ephedrine and caffeine (EC) combination has been widely used in human obesity treatment. It is known that this drug increases the metabolic rate in both animals and humans. Ephedrine is an agonist of both α and β-adrenoceptors; moreover, it induces norepinephrine release from sympathetic neurons. Caffeine increases both norepinephrine and dopamine release and stimulates the neuronal activity in several brain regions. We hypothesize that EC treatment might exert a specific effect on lipolysis and thermogenesis by stimulation of beta-3 adrenoreceptors on adipose tissue and by stimulating uncoupling of oxidative phosphorylation, i.e. energy being dissipated as heat rather than being converted to adenosine triphosphate (ATP)

Our study is a double-blind, placebo-controlled, 4-week trial to investigate the effect of hypocaloric diet alone or coupled to EC treatment of morbidly obese women on thermogenesis, expression of UCP 3 (in muscle tissue) and of beta-3 adrenoreceptors (in adipose tissue). Subjects are randomly assigned to EC (200/20 mg) or to placebo administered three times a day orally together with a energy-deficit diet (70% of resting energy expenditure), starting one month before undergoing bariatric surgery. Primary study endpoints are weight change analysed by intention to treat, changes in resting energy expenditure, UCP3 (long and short isoform), messenger ribonucleic acid (mRNA) levels in rectus abdominis and immunostaining for beta-3 adrenoreceptors in subcutaneous and omental adipose tissue. Also plasma epinephrine, norepinephrine, triglycerides, free fatty acids, glycerol, TSH, free thyroxine (fT4), free triiodothyronine (fT3) fasting glucose, insulin and homeostasis model assessment (HOMA) index, are measured at baseline and at the end of treatments.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Istituto Auxologico Italiano
• Collaborators: Università Politecnica delle Marche; University of Milan
• Treatments: Caffeine; Ephedrine; Pseudoephedrine

Criteria

Inclusion Criteria:

• pre-menopausal females

• body mass index ≥ 40 kg/m2

• with stable weight in the three month before the study

• scheduled for bariatric surgery

• in whom weight loss was clinically advisable before surgery to reduce surgical risk

• non-smokers or smoking less than 5 cigarettes per day

Exclusion Criteria:

• pregnancy

• ischaemic heart disease

• cardiac failure

• high blood pressure requiring drug treatment

• tachyarrhythmia

• sick sinus syndrome

• atrioventricular block

• two-bundle ventricular block

• cerebrovascular diseases

• occlusive peripheral artery disease

• renal failure

• current treatment with drugs that might affect metabolic rate (e.g. β-adrenergic blockers, thyroid hormones).