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

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.

Conditions

• Obesity

Interventions

DRUG

Caffeine

Patients are randomised to 30-day treatment with either EC (200/20mg t.i.d.) or placebo. The EC administration starts with an initial dose of 100/10 mg t.i.d. for the first week and then proceeds with the full dose of 200/20 mg t.i.d. Patients are hospitalised during the whole treatment period, at the metabolic unit of San Giuseppe Hospital-Istituto Auxologico Italiano at Piancavallo (VB, Italy). During the treatment period all patients are fed a hypocaloric diet (total energy content of \~70% of energy expenditure, as measured by indirect calorimetry), and containing 20% proteins, 55% carbohydrates, 25% fat half of which was monounsaturated, and 35 g/day fibres.

DRUG

Placebo

Patients are randomised to 30-day treatment with either EC (200/20mg t.i.d.) or placebo. The EC administration starts with an initial dose of 100/10 mg t.i.d. for the first week and then proceeds with the full dose of 200/20 mg t.i.d. Patients are hospitalised during the whole treatment period, at the metabolic unit of San Giuseppe Hospital-Istituto Auxologico Italiano at Piancavallo (VB, Italy). During the treatment period all patients are fed a hypocaloric diet (total energy content of \~70% of energy expenditure, as measured by indirect calorimetry), and containing 20% proteins, 55% carbohydrates, 25% fat half of which was monounsaturated, and 35 g/day fibres.

DRUG

Ephedrine

Patients are randomised to 30-day treatment with either EC (200/20mg t.i.d.) or placebo. The EC administration starts with an initial dose of 100/10 mg t.i.d. for the first week and then proceeds with the full dose of 200/20 mg t.i.d. Patients are hospitalised during the whole treatment period, at the metabolic unit of San Giuseppe Hospital-Istituto Auxologico Italiano at Piancavallo (VB, Italy). During the treatment period all patients are fed a hypocaloric diet (total energy content of \~70% of energy expenditure, as measured by indirect calorimetry), and containing 20% proteins, 55% carbohydrates, 25% fat half of which was monounsaturated, and 35 g/day fibres.

OTHER

Hypocaloric diet

Patients are randomised to 30-day treatment with either EC (200/20mg t.i.d.) or placebo. The EC administration starts with an initial dose of 100/10 mg t.i.d. for the first week and then proceeds with the full dose of 200/20 mg t.i.d. Patients are hospitalised during the whole treatment period, at the metabolic unit of San Giuseppe Hospital-Istituto Auxologico Italiano at Piancavallo (VB, Italy). During the treatment period all patients are fed a hypocaloric diet (total energy content of \~70% of energy expenditure, as measured by indirect calorimetry), and containing 20% proteins, 55% carbohydrates, 25% fat half of which was monounsaturated, and 35 g/day fibres.

Sponsors & Collaborators

• University of Milan

  collaborator OTHER

• Università Politecnica delle Marche

  collaborator OTHER

• Istituto Auxologico Italiano

  lead OTHER

Principal Investigators

• Maria L Petroni, MD · Istituto Auxologico Italiano

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

55 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2000-02-29

Primary Completion

2001-01-31

Completion

2007-11-30

Countries

• Italy

Study Locations