P1vital CNS Experimental Medicine : UNIVERSAL EATING MONITOR

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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 John Wilding, Dr Jason Halford and Prof Tim Kirkham 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. A validation study with the UEM has recently been completed using the licensed appetite-suppressant: the serotonin- and noradrenaline-reuptake inhibitor, sibutramine.

The study was an outpatient, double-blind, placebo-controlled trial, utilising a randomised within-subject design to evaluate the effects of sibutramine (at doses of 10 and 15mg given for 7 days) on food intake and energy expenditure in 30 obese women (BMI >30). Data collected by UEM were 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 were collected using the Deltratrac metabolic monitor. At day 7, sibutramine 10 mg and 15 mg reduced food intake by 16.6% and 22.3%, respectively (p < 0.001), compared with placebo. Sibutramine reduced eating rate compared with placebo rather than meal length (10 mg p < 0.05; 15 mg p < 0.001). In addition, sibutramine 10 mg significantly reduced hunger later in the meal (p < 0.05) and sibutramine 15 mg increased fullness early in the meal (p < 0.01), both of which are consistent with enhanced within-meal satiation. Sibutramine had little effect on resting metabolic rate, although 15 mg did significantly reduce respiratory quotient at several time points during the test day. These results provide novel evidence that decreased consumption of a test meal induced by sibutramine is primarily because of reduced eating rate, enhancing the deceleration in cumulative food intake within a meal associated with the development of satiety. Changes in within-meal appetite ratings appear particularly sensitive to drug-induced enhancement of satiation, and may provide key indices for assessing the therapeutic potential of novel anti-obesity drugs. This study demonstrates that the UEM model, which measures the microstructure of eating behaviour, is sufficiently sensitive to detect hypophagic and satiety-enhancing effects of novel compounds. Moreover, in this model of eating behaviour, changes were detected at doses not previously reported to affect food intake and eating behaviour, but that have shown weight loss efficacy. The effects of sibutramine on eating behaviour in this UEM study provide a reference standard against which novel, appetite-reducing, anti-obesity compounds can be assessed. We believe that drug induced changes in food intake and appetite measured by the UEM are a valid indicator of potential weight-reducing efficacy and that the potential for compound failure in later clinical phases could be significantly reduced by the use of the UEM model in early clinical studies of novel anti-obesity agents.