This week’s issue of The Lancet writes an account of the termination of the CRESCENDO trial of Rimonabant, formerly marketed as Acomplia. The Crescendo study by, Eric J. Topol, of Scripps Translational Science Institute, assessed whether Rimonabant (a previously approved weight loss medication) improved cardiovascular risk.
Covering 42 countries and 18,695 patients, the group was split in two with half chosen to take 20mg of Rimonabant while the other half were chosen to take a placebo. Rimonabant’s function is to block the cannabinoid 1 receptors – part of the body’s not very well understood endocannabinoid system. These CB1 receptors have a role to play in appetite. By blocking the CB1 receptors, appetite is suppressed and ultimately, weight is lost. Rimonabant has also been said to maintain good glucose levels and it has been shown to have a positive effect on cholesterol levels too.
The Crescendo trial was discontinued in November 2008 (after Acomplia was withdrawn from the prescribing list in the EU) as certain local health authorities were unhappy with suicide rates among those who were taking part in clinical trials. In the Crescendo trial there were 4 suicides from those taking the Rimonabant and 1 taking the placebo.
The number taking Rimonabant and died as a result of a cardiac illness, myocardial infarction or stroke was equal to the number of fatalities among those who were being treated with the placebo. However, there was a marked effect on neuropsychiatric processes, serious psychiatric effects and gastrointestinal problems associated with the taking of Rimonabant. Contrasting the effects with those of the placebo, Rimonabant caused substantially more instances.
To avoid these harmful effects at trial stage in the future, it has been suggested that genomics might be used to test such controversial drugs. S. Matthijs Boekholdt and Ron J. G. Peters, Academic Medical Centre, Amsterdam, said that if the trial had not been suspended, a massive improvement could have been made to revolutionise cardiovascular health and with only a small risk of serious effects accompanying it. It is this small risk which impeded completion of the trials but any preventative treatment for cardiovascular risk which can result in fatality, say Boekholdt and Peters, is deemed unacceptable.