Effects of intestinal Amarasate™ (a bitter hops extract) on gut function in healthy, lean volunteers.

The intervention in this study consists of an intraduodenal bolus administration of hop extract (Amarasate) or control solution, after which gut motility, gut hormone concentrations, appetite perceptions and energy intake will be measured. Studies will be carried out at the Clinical Research Facility, Adelaide Medical School, University of Adelaide, by team members trained in the required techniques and procedures. All tests will be performed while the participant attends the Research Facility, in response to the acute interventions described below, hence, no issues with compliance with the intervention are anticipated. Subjects enrolled into the study will receive, in randomized, double blind fashion either (i) 100 mg Amarasate extract, (ii) 250 mg Amarasate extract, or (iii) Canola oil (control) on 3 separate visits. Each visit will last 5hrs in duration, and will be separated by 3-7 days. Subjects will be asked to consume a standardised dinner meal (McCain beef lasagne) the night before each visit by no later than 6pm, and then refrain from oral consumption of solids and liquids, except water, as well as any medications. This will be confirmed in the morning of the study by questioning the participant. After fasting for 14 hrs overnight and refraining from exercise and alcohol for 24 hrs, subjects will arrive at the laboratory at 8am. Upon arrival, subjects will be intubated with a 17-channel manometric catheter that will be inserted through an anaesthetised nostril and allowed to pass through the stomach and into the duodenum by peristalsis. The manometric catheter consists of 16 side holes spaced at 1.5 cm intervals, measuring pressures in the antrum, pylorus and duodenum (APD pressures). An additional channel (with the side hole positioned approx 14 cm distal to the pylorus when the catheter is in position) is used for intraduodenal administration of amarasate or control. The correct positioning of the catheter will be maintained by continuous measurement of the transmucosal potential difference (TMPD) between the most distal antral channel and the most proximal duodenal channel. All manometric channels will be perfused with degassed, distilled water, except for the two TMPD channels, which will be perfused with degassed 0.9% saline, at 0.15 ml/min. An intravenous cannula will be placed into a right forearm vein for regular blood sampling to measure plasma hormone concentrations. Once the catheter has been positioned correctly, fasting motility will be monitored continuously, and immediately after the end of phase III activity of the fasting migrating motor complex (MMC), during a period of motor quiescence (t=-10 – -1 min), a ~9 ml venous blood sample (baseline) will be taken, and the subject will complete a visual analogue scale questionnaire (VAS) to assess appetite-related perceptions (fullness, hunger, etc.) and symptoms (nausea and bloating). At t = -1 min (during phase I of the MMC), the bolus dose (either (i), (ii), or (iii) as outlined above) will be administered in ~1 min. APD pressures will be measured continually over the following 180-min period. Blood samples will be collected and VASs completed every 10 min from t = 10 to 30 min, then every 15 min from t = 30 to 60 min, and then every 30 min until t = 180 min. At t = 180 min, the manometric catheter will be removed and subjects will be presented with a cold, buffet-style meal. Subjects will be allowed 30 min to freely consume food until they are comfortably full. At t = 210 min another blood sample will be taken, and VAS administered. The intravenous cannula will then be removed and subjects will be allowed to leave the laboratory. A total of 99 ml of blood will be taken on each study day (297 ml over all study visits).