None listed
Conditions
Brief summary
Emerging evidence of preclinical studies suggests that bitter substances in the gut can reduce appetite and slow the emptying of meals from the stomach, by stimulating GI hormone release. The purpose of this study is to determine whether stimulation of intestinal bitter taste receptors (BTRs) by non-caloric BTR agonists induces GI hormone secretion in humans and, if so, whether probenecid acts as an effective BTR antagonist. In this trial, we wish to investigate whether rectal infusion of a BTR agonist, denatonium benzoate (DB), stimulates the secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) and antagonism of BTR signalling by probenecid attenuates the GLP-1 and PYY responses induced by rectal administration of bitter tastants (i.e. DB and taurocholic acid (TCA, which is known to stimulate GLP-1 and PYY secretion humans and therefore will serve as a positive control).
Interventions
Following a screening visit, each subject will be studied on 5 occasions, separated by at least 7 days, in a double-blinded randomised order.
On each study day, an intravenous cannula will be inserted into a forearm vein for repeated blood sampling. The subject will then be positioned in the left lateral decubitus position, and the 20mL aqueous gel (1% carboxymethyl cellulose) containing DB (30mg), DB (30mg) + probenecid (456mg), TCA (3500mg), TCA (3500mg) + probenecid (456mg), or vehicle only,
Following a screening visit, each subject will be studied on 5 occasions, separated by at least 7 days, in a double-blinded randomised order. On each study day, an intravenous cannula will be inserted into a forearm vein for repeated blood sampling. The subject will then be positioned in the left lateral decubitus position, and the 20mL aqueous gel (1% carboxymethyl cellulose) containing DB (30mg), DB (30mg) + probenecid (456mg), TCA (3500mg), TCA (3500mg) + probenecid (456mg), or vehicle only, will be infused into the rectum via a soft catheter by a medically qualified investigator within 2 min and then be removed.
Sponsors
University of Adelaide
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy male and females aged 18 – 55 years Body mass index (BMI) 19 - 25 kg/m2 Haemoglobin above the lower limit of the normal range (ie. >135g/L for men and 115g/L for women), and ferritin above the lower limit of normal (ie. >30ng/mL for men and >20mg/mL for women)
Exclusion criteria
Use of any medication that may influence gastrointestinal motor function, body weight or appetite (e.g. antihypertensive drugs, domperidone and cisapride, anticholinergic drugs (e.g. atropine), metoclopramide, erythromycin, hyoscine, orlistat, green tea extracts, Astragalus, St. John's Wort etc.) Evidence of drug abuse, consumption of more than 20 g alcohol or 10 cigarettes on a daily basis History of gastrointestinal disease, including significant upper or lower gastrointestinal symptoms, pancreatitis, or previous gastrointestinal surgery (other than uncomplicated appendicectomy or cholecystectomy) Other significant illness, including epilepsy, cardiovascular or respiratory disease Impaired renal or liver function (as assessed by calculated creatinine clearance < 90 mL/min or abnormal liver function tests (> 2 times upper limit of normal range)) Donation of blood within the previous 3 months Participation in any other research studies within the previous 3 months Inability to give informed consent Female participants who are pregnant or planning for pregnancy, or are lactating Vegetarians
Outcome results
None listed