Inhibition Of VAP-1 by Caffeine In Healthy Human Volunteers (NOCTUA)
Research type
Research Study
Full title
A non-randomised, single centre phase I study to establish whether caffeine inhibits vascular adhesion protein-1 (VAP-1) in healthy human volunteers.
IRAS ID
147510
Contact name
David Adams
Contact email
Clinicaltrials.gov Identifier
Research summary
Worldwide, liver related morbidity and mortality continue to rise. It is the 5th commonest cause of death in the UK. Cirrhosis is the pathological process common to all causes of chronic liver disease causing scarring and leading to portal hypertension with potential to develop into cancer. Liver transplant is currently the only curative treatment for end stage chronic liver disease. Unfortunately its high demand has not been matched by an equivalent rise in liver donations and even when a transplant has occurred there are numerous lifestyle effects such as immunosuppression and kidney impairment thus outcome remains poor for many patients. Caffeine has been shown to have mortality benefit in humans and drinking two to three cups of coffee a day was clinically significant. It is known that enzymes such as vascular adhesion protein-1 (VAP-1) play an important role in mediating the interaction and binding of special immune cells called lymphocytes to liver endothelial cells. VAP-1 levels become elevated during chronic inflammation in blood vessels of the gut, tonsils, skin and synovium. Recently, soluble VAP-1 has been demonstrated to be elevated in certain liver diseases particularly alcoholic liver disease. We know from two recent papers (Olivieri and Tipton 2011, Che et al. 2012) that activity of the enzyme SSAO (Semicarbazide-sensitive amine oxidase) can be effectively blocked by caffeine. SSAO arises from the same family of enzymes as VAP-1 thus importantly shares transferable properties. Our hypothesis is that given the potential for caffeine to be used as a treatment in SSAO activity associated diseases it is important to see if the activity of SSAO can be inhibited in healthy humans too. If proven, the addition of caffeine for medicinal use would prove invaluable.
REC name
HSC REC A
REC reference
14/NI/1122
Date of REC Opinion
9 Dec 2014
REC opinion
Further Information Favourable Opinion