Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000503921
Ethics application status
Approved
Date submitted
8/04/2020
Date registered
23/04/2020
Date last updated
1/07/2021
Date data sharing statement initially provided
23/04/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects of intestinal Amarasate™ (a bitter hops extract) on gut function in healthy, lean volunteers.
Scientific title
Effects of intragastric Amarasate™ extract (bitter agonist), on upper gastrointestinal (GI) functions and energy intake in healthy, lean volunteers.
Secondary ID [1] 300893 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 Diabetes 316826 0
Healthy human gastrointestinal physiology
 316827 0
Obesity
 316828 0
Condition category
Condition code
Diet and Nutrition 315035 315035 0 0
Obesity
Oral and Gastrointestinal 315036 315036 0 0
Normal oral and gastrointestinal development and function
Metabolic and Endocrine 315037 315037 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention in this study consists of an intragastric bolus administration of either 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 Amarasate, at a dose of 250 mg, or Canola oil (control) on 2 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 six antral channels, a 4.5-cm pyloric sleeve sensor with two channels situated on the back, and seven duodenal channels, with all side holes positioned at 1.5-cm intervals, measuring pressures in the antrum, pylorus and duodenum. The most proximal antral channel is used for intragastric administration. 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 gastrointestinal symptoms (nausea and bloating). At t = -1 min (during phase I of the MMC), Amarasate or control will be administered, within 1 min. Antropyloroduodenal (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 (198 ml over all study visits).
Intervention code [1] 317216 0
Treatment: Other
Comparator / control treatment
Canola oil
Control group
Placebo

Outcomes
Primary outcome [1] 323339 0
Plasma concentrations of gastrointestinal hormones, e.g. CCK, GLP-1, PYY and ghrelin, will be assessed by Enzyme-linked Immunosorbent Assay (ELISA) or Radio Immunosorbent Assay (RIA).

This intervention is of an exploratory nature to characterise the effects of amarasate, at dose of 250 mg. As such, it is unknown which plasma concentrations of gastrointestinal hormones may prove to be of importance. Hence these have been grouped into one composite primary outcome.
Timepoint [1] 323339 0
At t = -10 min, 10 minute intervals from t= 10- 30 min, 15 min intervals from t= 30 - 60 min, 30 min intervals from t= 60 - 180 min, and at t= 210 min.
Primary outcome [2] 323340 0
Antropyloroduodenal pressures will be measured using a 17-channel manometric assembly (Dentsleeve, Mui Scientific).
Timepoint [2] 323340 0
Baseline (t = -10 - 0 min) and after intragastric administration (t = 0 - 180 min).
Secondary outcome [1] 381610 0
Energy intake at the buffet meal. The weight of the foods will be recorded before and after being offered to the subjects and energy intake and macronutrient composition calculated subsequently using commercially available software (Foodworks, Xyris Software, Highgate Hill, QLD, Australia).
Timepoint [1] 381610 0
180 min after the intragastric administration, for 30 minutes (t=180-210min).
Secondary outcome [2] 381611 0
Appetite sensations (hunger, fullness, desire to eat, amount of food the subject thinks they could eat) and gastrointestinal symptoms (nausea, bloating) will be measured using a 100mm Visual Analogue Scale (VAS) questionnaire. This questionnaire has been extensively employed in published studies conducted by the investigator.

This intervention is of an exploratory nature to characterise the effects of amarasate, at dose of 250 mg. As such, it is unknown which appetite sensations and gastrointestinal symptoms may prove to be of importance. Hence these have been grouped into one composite secondary outcome.
Timepoint [2] 381611 0
At t = -10 min, 10 minute intervals from t= 10- 30 min, 15 min intervals from t= 30 - 60 min, 30 min intervals from t= 60 - 180 min, and at t= 210 min.
Secondary outcome [3] 381612 0
Plasma concentrations of Insulin, Glucagon, C-peptide will be assessed by Enzyme-linked Immunosorbent Assay (ELISA) or Radio Immnunosorbent Assay (RIA).

This intervention is of an exploratory nature to characterise the effects of amarasate, at dose of 250 mg. As such, it is unknown which plasma concentrations of hormones may prove to be of importance. Hence these have been grouped into one composite secondary outcome.
Timepoint [3] 381612 0
At t = -10 min, 10 minute intervals from t= 10- 30 min, 15 min intervals from t= 30 - 60 min, 30 min intervals from t= 60 - 180 min, and at t= 210 min.

Eligibility
Key inclusion criteria
A total of 12 healthy, lean (BMI 19-25 kg/m2) male subjects, aged between 18 - 60 years will be included. Subjects will be required to be weight stable (ie <5% fluctuation) at study entry, which will be ascertained by a stable body weight in the preceding 4 weeks.
Minimum age
18 Years
Maximum age
60 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
Significant GI symptoms, disease or surgery
Use of prescribed or non-prescribed medications (including vitamins and herbal Supplements) which may affect energy metabolism, GI function, body weight or appetite (eg domperidone, cisapride, anticholinergic drugs (eg atropine), metoclopramide, erythromycin, hyoscine, orlistat, green tea extracts, Astragalus, St Johns Wort etc.)
Lactose intolerance/other food allergy(ies), including hops allergy, diagnosed idiopathic anaphylaxis or occupational exposure to hops (hops pickers, brewers)
Current gallbladder or pancreatic disease
Cardiovascular or respiratory diseases
Individuals with low ferritin levels (<30 ng/mL), or who have donated blood in the 12 weeks prior to taking part in the study
Any other illnesses as assessed by the investigator (including chronic illnesses not explicitly listed above)
High performance athletes
Current intake of > 2 standard drinks on > 5 days per week
Current smokers of cigarettes/cigars/marijuana
Recreational drug use
Current intake of any illicit substance
Vegetarians
Inability to tolerate nasogastric tube
Inability to comprehend study protocol
Restrained eaters (score >12 on the 3-factor eating questionnaire)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation involves contacting the holder of the randomisation table (study assistant) to inform them of the next subjects details and study dates. The unblinded study assistant is therefore responsible for allocating a randomly generated treatment sequence to the subject and preparing the intragastric bolus for administration on each study day.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation is generated using a randomization plan generator available at www.randomization.com
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Pharmacodynamics
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
28/04/2020
Actual
4/05/2020
Date of last participant enrolment
Anticipated
7/09/2020
Actual
7/07/2020
Date of last data collection
Anticipated
7/10/2020
Actual
20/07/2020
Sample size
Target
12
Accrual to date
Final
11
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 305344 0
Government body
Name [1] 305344 0
National Health and Medical Research Council (NHMRC)
Country [1] 305344 0
Australia
Primary sponsor type
Individual
Name
Professor Christine Feinle-Bisset
Address
Adelaide Medical School | Faculty of Health and Medical Sciences
The University of Adelaide
Level 5, Adelaide Health and Medical Sciences Building
Cnr North Terrace and George Street
Adelaide
South Australia 5005
Country
Australia
Secondary sponsor category [1] 305712 0
Individual
Name [1] 305712 0
Professor Michael Horowitz
Address [1] 305712 0
Adelaide Medical School | Faculty of Health and Medical Sciences
The University of Adelaide
Level 6, Adelaide Health and Medical Sciences Building
Cnr North Terrace and George Street
Adelaide
South Australia 5005
Country [1] 305712 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305677 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 305677 0
Ethics committee country [1] 305677 0
Australia
Date submitted for ethics approval [1] 305677 0
17/02/2020
Approval date [1] 305677 0
10/03/2020
Ethics approval number [1] 305677 0
CALHN Reference number: R20180631, HREC reference number: HREC/18/CALHN/416

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 101194 0
Prof Christine Feinle-Bisset
Address 101194 0
Adelaide Medical School | Faculty of Health and Medical Sciences
The University of Adelaide
Level 5, Adelaide Health and Medical Sciences Building
Cnr North Terrace and George Street
Adelaide
South Australia 5005
Country 101194 0
Australia
Phone 101194 0
+61 8 8313 6053
Fax 101194 0
Email 101194 0
[email protected]
Contact person for public queries
Name 101195 0
Christine Feinle-Bisset
Address 101195 0
Adelaide Medical School | Faculty of Health and Medical Sciences
The University of Adelaide
Level 5, Adelaide Health and Medical Sciences Building
Cnr North Terrace and George Street
Adelaide
South Australia 5005
Country 101195 0
Australia
Phone 101195 0
+61 8 8313 6053
Fax 101195 0
Email 101195 0
[email protected]
Contact person for scientific queries
Name 101196 0
Christine Feinle-Bisset
Address 101196 0
Adelaide Medical School | Faculty of Health and Medical Sciences
The University of Adelaide
Level 5, Adelaide Health and Medical Sciences Building
Cnr North Terrace and George Street
Adelaide
South Australia 5005
Country 101196 0
Australia
Phone 101196 0
+61 8 8313 6053
Fax 101196 0
Email 101196 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.