Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000107729p
Ethics application status
Submitted, not yet approved
Date submitted
3/09/2021
Date registered
24/01/2022
Date last updated
24/01/2022
Date data sharing statement initially provided
24/01/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of appetite suppressant treatment on hunger and rebound eating in fasting women
Scientific title
The effect of a gut targeted appetite suppressant on factors relating to appetite, craving, and rebound eating during a 24h fast in women
Secondary ID [1] 305166 0
Nil known
Universal Trial Number (UTN)
U1111-1268-8732
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obesity 323435 0
Condition category
Condition code
Diet and Nutrition 320988 320988 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Subjects will consume, in a randomized, double-blind fashion (cross-over design), gastric digestion resistant capsules (DRCaps, Capsugel) containing i) 500mg (2x250mg) super critical CO2 extract of hops flower (Amarasate), ii) 200mg (2x100mg) Amarasate, or iii) matching placebo (control). Each subject will receive half the total treatment twice during a given study day (at 10:00 hr and 14:00 hr), and treatments i, ii, and iii will occur on separate occasions. Study visits will be separated by at least 7 days. During study laboratory visits, the lead researchers will be present to closely monitor adherence to study protocol. At 18:00 hr on the evening prior to study day, participants will be instructed to not consume any food or drinks other than water, with compliance determined by participant self-report. On each study day, subjects will begin the laboratory based assessments at 10:00 hr (t=0 min) and will complete visual analogue based questionnaires relating to appetite, food cravings, side effects, and fast difficulty throughout the study day, and have blood taken for measurement of appetite related hormones (Ghrelin and LEAP-2), blood glucose and ketones, and progesterone levels. Immediately following the first questionnaire and blood sample, subjects will ingest the first treatment capsules of either (i) 250mg Amarasate (ii), 100mg Amarasate or (iii) control, with 250 ml of water, within 2 mins. VAS questionnaires will be collected 30-min intervals from 10:00 (t=0 min) to 18:00 hr (t=480min) of the study day. Blood samples will be taken at 10:00 for all blood measures, at 12:00 for blood glucose and ketones and appetite related hormones, at 14:00 hr for blood glucose and ketones, at 16:00 hr for blood glucose and ketones, and at 18:00 hr for blood glucose and ketones and appetite related hormones. At 14:00h subjects will be giving the second treatment capsule (matched to the one given at 10:00h) of either (i) 250mg Amarasate (ii), 100mg Amarasate or (iii) control, with 250 ml of water and to be consumed within 2 mins. VAS and food craving questionnaires continue as described above. At 18:00 hr, participants will be presented a high carbohydrate rice based ad libitum meal and asked to eat until comfortably full. At 18:30 hr subjects will be allowed to leave the laboratory.
Intervention code [1] 321592 0
Treatment: Drugs
Comparator / control treatment
Placebo capsules containing canola oil for within group comparison
Control group
Placebo

Outcomes
Primary outcome [1] 328798 0
Changes in subjective measures of appetite as determined by Visual Analogue Scale (VAS) for Hunger
Timepoint [1] 328798 0
VAS measures will be taken through the 16h to 24h fasting period every 30 mins. Specifically at 1000h (t=0), 1030h, 1100h, 1130h, 1200h, 1230h, 1300h, 1330h 1400h, 1430h, 1500h, 1530h, 1600h, 1630h, 1700h, 1730h and 1800h (t=480)
Primary outcome [2] 328799 0
Changes in subjective measures of appetite as determined by Visual Analogue Scale (VAS) for Fullness
Timepoint [2] 328799 0
VAS measures will be taken through the 16h to 24h fasting period every 30 mins. Specifically at 1000h (t=0), 1030h, 1100h, 1130h, 1200h, 1230h, 1300h, 1330h 1400h, 1430h, 1500h, 1530h, 1600h, 1630h, 1700h, 1730h and 1800h (t=480)
Primary outcome [3] 328800 0
Changes in subjective measures of appetite as determined by Visual Analogue Scale (VAS) for Satisfaction
Timepoint [3] 328800 0
VAS measures will be taken through the 16h to 24h fasting period every 30 mins. Specifically at 1000h (t=0), 1030h, 1100h, 1130h, 1200h, 1230h, 1300h, 1330h 1400h, 1430h, 1500h, 1530h, 1600h, 1630h, 1700h, 1730h and 1800h (t=480)
Secondary outcome [1] 400412 0
Changes in subjective measures of appetite as determined by Visual Analogue Scale (VAS) for Thoughts of Food

Note: This is a primary outcome.
Timepoint [1] 400412 0
VAS measures will be taken through the 16h to 24h fasting period every 30 mins. Specifically at 1000h (t=0), 1030h, 1100h, 1130h, 1200h, 1230h, 1300h, 1330h 1400h, 1430h, 1500h, 1530h, 1600h, 1630h, 1700h, 1730h and 1800h (t=480)
Secondary outcome [2] 400413 0
Changes in subjective measures of possible side-effects as determined by Visual Analogue Scale (VAS) for Thirst
Timepoint [2] 400413 0
VAS measures will be taken through the 16h to 24h fasting period every 30 mins. Specifically at 1000h (t=0), 1030h, 1100h, 1130h, 1200h, 1230h, 1300h, 1330h 1400h, 1430h, 1500h, 1530h, 1600h, 1630h, 1700h, 1730h and 1800h (t=480)
Secondary outcome [3] 400414 0
Changes in subjective measures of possible side-effects as determined by Visual Analogue Scale (VAS) for Energy
Timepoint [3] 400414 0
VAS measures will be taken through the 16h to 24h fasting period every 30 mins. Specifically at 1000h (t=0), 1030h, 1100h, 1130h, 1200h, 1230h, 1300h, 1330h 1400h, 1430h, 1500h, 1530h, 1600h, 1630h, 1700h, 1730h and 1800h (t=480)
Secondary outcome [4] 400415 0
Changes in subjective measures of possible side-effects as determined by Visual Analogue Scale (VAS) for Nausea
Timepoint [4] 400415 0
VAS measures will be taken through the 16h to 24h fasting period every 30 mins. Specifically at 1000h (t=0), 1030h, 1100h, 1130h, 1200h, 1230h, 1300h, 1330h 1400h, 1430h, 1500h, 1530h, 1600h, 1630h, 1700h, 1730h and 1800h (t=480)
Secondary outcome [5] 400418 0
Changes in subjective measures of possible side-effects as determined by Visual Analogue Scale (VAS) for Sickness
Timepoint [5] 400418 0
VAS measures will be taken through the 16h to 24h fasting period every 30 mins. Specifically at 1000h (t=0), 1030h, 1100h, 1130h, 1200h, 1230h, 1300h, 1330h 1400h, 1430h, 1500h, 1530h, 1600h, 1630h, 1700h, 1730h and 1800h (t=480)
Secondary outcome [6] 400419 0
Changes in subjective measures of possible side-effects as determined by Visual Analogue Scale (VAS) for Vomiting
Timepoint [6] 400419 0
VAS measures will be taken through the 16h to 24h fasting period every 30 mins. Specifically at 1000h (t=0), 1030h, 1100h, 1130h, 1200h, 1230h, 1300h, 1330h 1400h, 1430h, 1500h, 1530h, 1600h, 1630h, 1700h, 1730h and 1800h (t=480)
Secondary outcome [7] 400420 0
Changes in subjective measures of possible side-effects as determined by Visual Analogue Scale (VAS) for Bloating
Timepoint [7] 400420 0
VAS measures will be taken through the 16h to 24h fasting period every 30 mins. Specifically at 1000h (t=0), 1030h, 1100h, 1130h, 1200h, 1230h, 1300h, 1330h 1400h, 1430h, 1500h, 1530h, 1600h, 1630h, 1700h, 1730h and 1800h (t=480)
Secondary outcome [8] 400421 0
Changes in subjective measures of possible side-effects as determined by Visual Analogue Scale (VAS) for Crap/Discomfort
Timepoint [8] 400421 0
VAS measures will be taken through the 16h to 24h fasting period every 30 mins. Specifically at 1000h (t=0), 1030h, 1100h, 1130h, 1200h, 1230h, 1300h, 1330h 1400h, 1430h, 1500h, 1530h, 1600h, 1630h, 1700h, 1730h and 1800h (t=480)
Secondary outcome [9] 400422 0
Changes in subjective measures of possible side-effects as determined by Visual Analogue Scale (VAS) for Heart Burn
Timepoint [9] 400422 0
VAS measures will be taken through the 16h to 24h fasting period every 30 mins. Specifically at 1000h (t=0), 1030h, 1100h, 1130h, 1200h, 1230h, 1300h, 1330h 1400h, 1430h, 1500h, 1530h, 1600h, 1630h, 1700h, 1730h and 1800h (t=480)
Secondary outcome [10] 400424 0
Changes in subjective measures of compliance as determined by Visual Analogue Scale (VAS) for Difficulty in maintaining fast,
Timepoint [10] 400424 0
VAS measures will be taken through the 16h to 24h fasting period every 30 mins. Specifically at 1000h (t=0), 1030h, 1100h, 1130h, 1200h, 1230h, 1300h, 1330h 1400h, 1430h, 1500h, 1530h, 1600h, 1630h, 1700h, 1730h and 1800h (t=480)
Secondary outcome [11] 400427 0
Changes in subjective measures of compliance as determined by Visual Analogue Scale (VAS) for Prospective thoughts of future compliance to a fast,
Timepoint [11] 400427 0
VAS measures will be taken through the 16h to 24h fasting period every 30 mins. Specifically at 1000h (t=0), 1030h, 1100h, 1130h, 1200h, 1230h, 1300h, 1330h 1400h, 1430h, 1500h, 1530h, 1600h, 1630h, 1700h, 1730h and 1800h (t=480)
Secondary outcome [12] 400428 0
Changes in subjective measures of compliance as determined by Visual Analogue Scale (VAS) for Current thought of compliance to Fast,
Timepoint [12] 400428 0
VAS measures will be taken through the 16h to 24h fasting period every 30 mins. Specifically at 1000h (t=0), 1030h, 1100h, 1130h, 1200h, 1230h, 1300h, 1330h 1400h, 1430h, 1500h, 1530h, 1600h, 1630h, 1700h, 1730h and 1800h (t=480)
Secondary outcome [13] 400429 0
Changes in subjective measures of compliance as determined by Visual Analogue Scale (VAS) for Fast-Related Side effects
Timepoint [13] 400429 0
VAS measures will be taken through the 16h to 24h fasting period every 30 mins. Specifically at 1000h (t=0), 1030h, 1100h, 1130h, 1200h, 1230h, 1300h, 1330h 1400h, 1430h, 1500h, 1530h, 1600h, 1630h, 1700h, 1730h and 1800h (t=480)
Secondary outcome [14] 400433 0
Changes in subjective measures of food craving as determined by Visual Analogue Scale (VAS) for craving for foods (general)
Timepoint [14] 400433 0
VAS measures will be taken through the 16h to 24h fasting period every 30 mins. Specifically at 1000h (t=0), 1030h, 1100h, 1130h, 1200h, 1230h, 1300h, 1330h 1400h, 1430h, 1500h, 1530h, 1600h, 1630h, 1700h, 1730h and 1800h (t=480)
Secondary outcome [15] 400434 0
Changes in subjective measures of food craving as determined by Visual Analogue Scale (VAS) for craving for sugary (sweet) foods
Timepoint [15] 400434 0
VAS measures will be taken through the 16h to 24h fasting period every 30 mins. Specifically at 1000h (t=0), 1030h, 1100h, 1130h, 1200h, 1230h, 1300h, 1330h 1400h, 1430h, 1500h, 1530h, 1600h, 1630h, 1700h, 1730h and 1800h (t=480)
Secondary outcome [16] 400435 0
Changes in subjective measures of food craving as determined by Visual Analogue Scale (VAS) for craving for salty foods
Timepoint [16] 400435 0
VAS measures will be taken through the 16h to 24h fasting period every 30 mins. Specifically at 1000h (t=0), 1030h, 1100h, 1130h, 1200h, 1230h, 1300h, 1330h 1400h, 1430h, 1500h, 1530h, 1600h, 1630h, 1700h, 1730h and 1800h (t=480)
Secondary outcome [17] 400436 0
Changes in subjective measures of food craving as determined by Visual Analogue Scale (VAS) for craving for fatty foods
Timepoint [17] 400436 0
VAS measures will be taken through the 16h to 24h fasting period every 30 mins. Specifically at 1000h (t=0), 1030h, 1100h, 1130h, 1200h, 1230h, 1300h, 1330h 1400h, 1430h, 1500h, 1530h, 1600h, 1630h, 1700h, 1730h and 1800h (t=480)
Secondary outcome [18] 400437 0
Changes in subjective measures of food craving as determined by Visual Analogue Scale (VAS) for craving for savoury foods
Timepoint [18] 400437 0
VAS measures will be taken through the 16h to 24h fasting period every 30 mins. Specifically at 1000h (t=0), 1030h, 1100h, 1130h, 1200h, 1230h, 1300h, 1330h 1400h, 1430h, 1500h, 1530h, 1600h, 1630h, 1700h, 1730h and 1800h (t=480)
Secondary outcome [19] 400438 0
Changes in subjective measures of food craving as determined by Visual Analogue Scale (VAS) for craving for spicy foods
Timepoint [19] 400438 0
VAS measures will be taken through the 16h to 24h fasting period every 30 mins. Specifically at 1000h (t=0), 1030h, 1100h, 1130h, 1200h, 1230h, 1300h, 1330h 1400h, 1430h, 1500h, 1530h, 1600h, 1630h, 1700h, 1730h and 1800h (t=480)
Secondary outcome [20] 400439 0
Changes in subjective measures of food craving as determined by Visual Analogue Scale (VAS) for craving for bitter foods
Timepoint [20] 400439 0
VAS measures will be taken through the 16h to 24h fasting period every 30 mins. Specifically at 1000h (t=0), 1030h, 1100h, 1130h, 1200h, 1230h, 1300h, 1330h 1400h, 1430h, 1500h, 1530h, 1600h, 1630h, 1700h, 1730h and 1800h (t=480)
Secondary outcome [21] 400445 0
Blood Glucose
Timepoint [21] 400445 0
Blood measures will be taken through the 16h to 24h fasting period every 120 mins. Specifically at 1000h (t=0), 1200h, 1400h, 1600h, and 1800h (t=480).
Secondary outcome [22] 400446 0
Blood Ketone Bodies
Timepoint [22] 400446 0
Blood measures will be taken through the 16h to 24h fasting period every 120 mins. Specifically at 1000h (t=0), 1200h, 1400h, 1600h, and 1800h (t=480).
Secondary outcome [23] 400447 0
Liver-enriched antimicrobial peptide-2 (LEAP-2)
Timepoint [23] 400447 0
Blood measures will be taken three times during the 16h to 24h fasting period. Specifically at 1000h (t=0), 1200h, and 1800h (t=480).
Secondary outcome [24] 400448 0
Ghrelin
Timepoint [24] 400448 0
Blood measures will be taken through the 16h to 24h fasting period every 120 mins. Specifically at 1000h (t=0), 1200h, 1400h, 1600h, and 1800h (t=480).
Secondary outcome [25] 400449 0
Energy intake - immediate. Participants will be presented with pre-weighed plates of food and asked to eat until comfortably. Plates will then be reweighed and energy intake will be determined.
Timepoint [25] 400449 0
Energy intake at an ad libitum meal presented at the breaking of the 24h fast will be assessed
Secondary outcome [26] 400450 0
Energy intake - 24h
Timepoint [26] 400450 0
Energy intake for the 24h following the 24h fast will be assessed by food diary.

Eligibility
Key inclusion criteria
Females
Aged 18-40 years
BMI 18.5-25kg/m2
Premenopausal
Normal gross gastrointestinal tract anatomy, as ascertained by self-report
Generally healthy, as ascertained by self-report
Regularly eat breakfast and lunch and dinner, as determined by self-reporting.
Regular menstrual cycle as ascertained by self-report
Minimum age
18 Years
Maximum age
40 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Any medical conditions or medications known to affect appetite -related parameters, including depression, diabetes and glucose intolerance or supplements that regulate appetite.
Participation in an active diet program and/or loss/gain of >10% body weight within the last 6 months
Smoker or ex-smoker who quit within the last 6 months
Hypersensitivities or allergies to any ingredients included in the study capsules
Dislike and/or unwilling to consume items listed as study foods
Unwilling/unable to comply with study protocol
Conditions effecting the gastrointestinal tract
Participating in another clinical intervention trial
Abnormal hunger and meal patterns, as ascertained by self-assessment
Any medical condition that may affect ability to safely participate in a 24h fast.
Frequently take part in fasting or intermittent fasting
Trying or likely to get pregnant
Likely or planning to either start or stop taking hormonal-based contraception during the trial.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Eligible volunteers are assigned a subject number and randomised onto a treatment visit schedule based on a Latin square design balanced for order of presentation and carry-over effect. Treatments will be assigned a code and aliquoted into sealed/opaque containers with only the treatment code visible. The treatment code will be held by 2 scientist who are not responsible for treatment dispensing or data collection. The unblinded scientist(s) are responsible for allocating a random treatment position to the volunteers and preparing the study treatments for dispensing.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation plan for assigning volunteers onto the Latin square design is generated using a randomization plan generator available at https://www.randomizer.org/
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
Efficacy
Statistical methods / analysis
Subjective VAS data will be analyzed as a mixed effects model using the Glimmix procedure in SAS (SAS: PROC MIXED, SAS Institute Inc, Cary, NC). To take account of the complex cross-over design, panellist and time within panellist will be treated as random effects with an auto regressive order 1 (AR1) covariance structure specified to model the residual correlations due to repeated measurements within a session. Visit number, time, treatment, and the treatment by time interaction will be included as fixed effects and tested using Type 3 sums of squares with Kenward-Roger degrees of freedom. Predicted means will be produced and pair-wise comparisons amongst treatments within a time point will be tested if the treatment by time interaction are statistically significant at the 5% level (p < 0.05). If no statistically significant differences are present between any of the treatment groups at baseline time point for any of the primary outcome appetite measures examined, datasets will then be normalized to the baseline reading within a subject and day combination and the full set of analyses repeated. The area under the curve (AUC) for each subject and visit combination will be calculated by numerical integration using Simpson’s rule. Energy intake at the ad libitum meal, Energy intake during the 24h post fast period, and blood ghrelin and leap2 concentrations will be analysed by ANOVA (SAS).
A power analysis was performed to provide estimates of variance components using data from Deloose et al 2017 where an intra-gastric gavage of the exceedingly bitter denatonium was given and VAS or hunger and fullness were measured. Calculations were done on the primary end point of VAS for changes in hunger. In the current study it is anticipated that 24-30 participants will be required to complete the 3 treatment days. The model based upon an estimated error variance taken from Deloose et al 2017 and estimated, using power of 0.8 suggests that the number of subjects required is estimated to fall between 24-30 subjects. Given the potential for participants to withdraw from the study, recruiting 30 people will allow for 80% power even after potential withdraws.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
20/02/2022
Actual
Date of last participant enrolment
Anticipated
20/03/2022
Actual
Date of last data collection
Anticipated
30/06/2022
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment outside Australia
Country [1] 24088 0
New Zealand
State/province [1] 24088 0
Auckland

Funding & Sponsors
Funding source category [1] 309554 0
Government body
Name [1] 309554 0
Callaghan Innovation
Country [1] 309554 0
New Zealand
Primary sponsor type
Other
Name
The New Zealand Institute for Plant and Food Research
Address
Plant and Food Research
120 Mount Albert Road,
Mount Albert,
Sandringham 1025
Auckland
New Zealand
Country
New Zealand
Secondary sponsor category [1] 310600 0
None
Name [1] 310600 0
Address [1] 310600 0
Country [1] 310600 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 309334 0
Northern B Health and Disability Ethics Committee
Ethics committee address [1] 309334 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140

Street address:
133 Molesworth Street
Thorndon
Wellington 6011
Ethics committee country [1] 309334 0
New Zealand
Date submitted for ethics approval [1] 309334 0
21/09/2021
Approval date [1] 309334 0
Ethics approval number [1] 309334 0

Summary
Brief summary
Obesity is associated with increased risk of a number of diseases including diabetes, heart disease, hypertension, and cancer. Traditional lifestyle treatments for obesity have focused on diet as both a preventative and treatment option and although diet has proven to be effective, recent discoveries have suggested that an intermittent fasting diet regime potentially offers greater health benefits when compared to classically prescribed diets.
Intermittent fasting has been shown to be effective for the reduction of body weight, to decrease pro-inflammatory proteins and blood glucose levels, reduce heart rate, and to reduce blood pressure and insulin levels. However, intermittent fasting results in increased feeling of hunger during the fasting period (specifically during the 16-24h period) that may affect compliance to the intermittent fasting diet regime, and results in a certain degree of rebound eating post fast. The addition of an appetite suppressant to an intermittent fasting diet may reduce increased hunger levels and improve compliance.
We have recently demonstrated that the gastrointestinal delivery of a highly bitter, non-nutritive, hops extract can reduce subjective ratings of hunger experienced during the last 8h of a 24h water only fast in healthy men. We hypothesise that consumption of this same extract will also reduce subjective rating of hunger in females, and that this decrease will likely be linked to changes in the pro-appetite hormone ghrelin and to changes in energy substrate utilisation. To test this hypothesis 30 healthy females will be recruited into a randomised, double-blind, placebo controlled, cross-over study designed to investigate the acute effect of a twice daily (10am, 2pm) high (2 x 250 mg) or low (2 x 100 mg) dose of the extract verses a placebo (2 x vehicle control) on subjective ratings of appetite, subjective assessment of fast compliance, food cravings, blood glucose and ketone levels, ghrelin and leap-2 blood concentrations, and rebound eating.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 113802 0
Dr Edward Walker
Address 113802 0
The New Zealand Institute for Plant & Food Research.
Private Bag 92169, Auckland Mail Centre, Auckland, 1142, New Zealand
Country 113802 0
New Zealand
Phone 113802 0
+64 9 925 7050
Fax 113802 0
Email 113802 0
[email protected]
Contact person for public queries
Name 113803 0
Dr Edward Walker
Address 113803 0
The New Zealand Institute for Plant & Food Research.
Private Bag 92169, Auckland Mail Centre, Auckland, 1142, New Zealand
Country 113803 0
New Zealand
Phone 113803 0
+64 9 925 7050
Fax 113803 0
Email 113803 0
[email protected]
Contact person for scientific queries
Name 113804 0
Dr Edward Walker
Address 113804 0
The New Zealand Institute for Plant & Food Research.
Private Bag 92169, Auckland Mail Centre, Auckland, 1142, New Zealand
Country 113804 0
New Zealand
Phone 113804 0
+64 9 925 7050
Fax 113804 0
Email 113804 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
This is for two reasons.
1 That our ethical application requires all data generated will only be used only for this study. However, if required, additional consent can be sought to allow other studies to access this data.
2. There may be commercial restrictions on this data.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

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No additional documents have been identified.