P1vital
CNS Experimental Medicine : OBESITY
Background
The WHO, governmental
and health agencies have publicised the global obesity epidemic,
affecting children, adolescents and adults, as one of the
principal health concerns facing the world’s population
today. Indeed, by 2025, the WHO estimates that obesity will
emerge as a more serious world problem than malnutrition.
Obesity is defined as a condition of abnormal or excessive
fat accumulation and increases the risk of developing type
II diabetes, coronary heart disease, hypertension, osteoarthritis
and some cancers. The fundamental cause of obesity is the
excess of energy intake over energy expenditure. Classification
of obesity is determined through measurement of the body mass
index (BMI), which is calculated by dividing body weight (kg)
by height squared (m2). A value in excess of 30 indicates
that the patient is obese.
It is estimated that over 250 million people suffer from obesity
worldwide. The US has the greatest prevalence of obesity with
up to 35% of the population defined as obese, and 54% defined
as overweight. The UK has one of the highest rates of obesity
in Europe, with 20% of the population defined as obese and
over 50% defined as overweight.
The development of safe and effective therapeutic interventions
is imperative, with the aim to achieve weight losses which
can be sustained sufficiently to reduce major health risks.
One of the effective means to help loss of weight, as part
of a comprehensive programme, is to prescribe drug treatments
designed specifically to reduce appetite and food consumption,
without significant side-effects.
At present drug treatment for obesity is limited to two products
that have recently entered the market. Orlistat is a lipase
inhibitor that works by preventing the breakdown and, therefore,
absorption of fat in the intestinal system. However, its utility
is limited by side effect problems including sudden faecal
urgency. Sibutramine is a serotonin-noradrenaline reuptake
inhibitor that affects brain mechanisms of satiety; however,
the drug also affects the cardiovascular system which limits
its utility.
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Universal Eating Monitor Model
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Despite new drug approvals, there is still a medical
need for improved therapies for obesity. Similarly, a need
exists for human experimental model systems which enable novel
drug therapies (already demonstrated to be safe in Phase 1
trials) to be rapidly screened for efficacy. P1vital
in collaboration with the University of Liverpool has established
a laboratory for the study of human ingestive behaviour and
has developed an automated method to measure food intake and
subjective ratings of food palatability, hunger and fullness.
P1vital is working
with Prof Steve Cooper and Prof John Wilding who have extensive
expertise in measurement of ingestive behaviour, metabolic
rate and energy expenditure, access to obese patients and
clinical trial experience with anti-obesity drugs. Together
we have developed a customized programme (Universal Eating
Monitor (UEM) model) which provides a robust, objective measure
of anti-obesity treatment interventions, ideally suited to
the evaluation of novel drug therapies. Studies are currently
underway to validate the UEM model with the licensed appetite-suppressant:
the serotonin- and noradrenaline-reuptake inhibitor, sibutramine.
The initial sibutramine study is an outpatient, double-blind,
placebo-controlled study, utilising a randomised within-subjects
design to evaluate the effects of sibutramine (at doses of
10 and 15mg) versus placebo control in terms of food intake
and energy expenditure in 36 obese female patients (BMI >30).
Data collected by UEM will be analysed to determine the effects
of the two sibutramine treatments on total food intake (energy)
in the test meal, the rate of consumption throughout the meal,
the duration of eating, and subjective ratings of palatability,
hunger and fullness. Simultaneous measurements of metabolic
rate will be collected using the Deltratrac metabolic monitor.
Effects on energy intake and expenditure will be evaluated
in relation to concentrations of active sibutramine metabolites
measured in blood samples. These data will provide a more
complete characterisation of sibutramine's anti-obesity effects
than currently available and will provide a standard set of
measures against which to compare potential novel anti-obesity
drugs in an appropriate laboratory setting. Successful completion
of this study (which is scheduled for 2Q 2006) will demonstrate
the utility, specificity and sensitivity of our automated,
quantitative measurement approach using the UEM |
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For more information on
the UEM model or to discuss obesity studies contact Info@p1vital.com
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