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Trial registered on ANZCTR


Registration number
ACTRN12616000134426
Ethics application status
Approved
Date submitted
2/02/2016
Date registered
5/02/2016
Date last updated
5/02/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
Gastric emptying and gut hormone secretion in anorexia nervosa: effects of refeeding
Scientific title
Effects of an oral mixed-nutrient meal on gastrointestinal hormone release, gastric emptying and appetite perceptions over a 3-week refeeding period in adolescent anorexia nervosa
Secondary ID [1] 288465 0
Nil known
Universal Trial Number (UTN)
U1111-1179-1231
Trial acronym
REGAiN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anorexia nervosa 297497 0
Starvation 297498 0
Condition category
Condition code
Mental Health 297686 297686 0 0
Eating disorders
Diet and Nutrition 297687 297687 0 0
Other diet and nutrition disorders
Metabolic and Endocrine 297688 297688 0 0
Normal metabolism and endocrine development and function

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Adolescent participants with anorexia nervosa (AN) (age 12-19 years) will be recruited during their inpatient admission at the Children’s Hospital at Westmead and Westmead Hospital. They will be studied on 3 separate occasions during their nutritional rehabilitation, at baseline (within 5 days of admission), and one and two weeks post-baseline. Their results will be compared to age-matched healthy-weight adolescent control participants assessed on one occasion. On each study day, participants in both the AN and control groups will undergo indirect calorimetry to assess energy expenditure. After this, they will receive an oral test meal of 2 Weetbix with 150mL full cream milk, an apple and a 250 mL full cream milk drink (2002kJ, 65.16g CHO, 19.12g protein, 14.92g fat) , following which, GI hormones and appetite perceptions will be measured. Gastric emptying will also be measured on all study days.
Intervention code [1] 293799 0
Not applicable
Comparator / control treatment
Healthy age-match control group will also be studied undertaking the same assessments.
Control group
Active

Outcomes
Primary outcome [1] 297224 0
Rate of gastric emptying, as determined by 13C-Octanoic acid breath test in response to a mixed nutrient test meal.
Timepoint [1] 297224 0
Measured over 2 hours, every 5 minutes in the first hour, and every 15 minutes in the second hour, at the baseline assessment, and 1 and 2 weeks post-baseline.
Primary outcome [2] 297225 0
Blood glucose response to a mixed nutrient test meal
Timepoint [2] 297225 0
Measured at t=0, 30, 60 and 120 minutes after the test meal, at the baseline study assessment as well as 1 and 2 weeks post-baseline.
Primary outcome [3] 297226 0
PYY concentration in response to a mixed nutrient test meal.
Timepoint [3] 297226 0
Measured at t=0, 30, 60 and 120 minutes after the test meal, at the baseline study assessment as well as 1 and 2 weeks post-baseline.
Secondary outcome [1] 320396 0
Appetite perceptions in response to the mixed nutrient test meal, measured via visual analogue scales.
Timepoint [1] 320396 0
Measured at t=0, 30, 60 and 120 minutes after the test meal, at the baseline study assessment as well as 1 and 2 weeks post-baseline.
Secondary outcome [2] 320397 0
Multiplex analysis of gastrointestinal hormone concentrations (insulin, glucagon, 3-OMG, ghrelin, GLP-1, GIP, C-Peptide, CCK) as a composite analysis in response to the mixed nutrient test meal.
Timepoint [2] 320397 0
Measured at t=0, 30, 60 and 120 minutes after the test meal, at the baseline study assessment as well as 1 and 2 weeks post-baseline.
Secondary outcome [3] 320398 0
Basal metabolic rate and respiratory quotient measured via indirect calorimetry, as a composite outcome,
Timepoint [3] 320398 0
Measured at baseline study assessment as well as 1 and 2 weeks post-baseline.
Secondary outcome [4] 320399 0
Gastrointestinal symptoms in response to the mixed nutrient test meal, measured via the Gastrointestinal Symptom Score.
Timepoint [4] 320399 0
Measured at t=0, 30, 60 and 120 minutes after the test meal, at the baseline study assessment as well as 1 and 2 weeks post-baseline.
Secondary outcome [5] 320400 0
State anxiety levels in response to the mixed nutrient test meal, measured via the State & Trait Anxiety Inventory (STAI)
Timepoint [5] 320400 0
Measured at t=0, 30, 60 and 120 minutes after the test meal, at the baseline study assessment as well as 1 and 2 weeks post-baseline.
Secondary outcome [6] 320401 0
Food fear levels, measured by the Food Fear Show and Food Phobia Scale.
Timepoint [6] 320401 0
Measured at the baseline study assessment as well as 1 and 2 weeks post-baseline.

Eligibility
Key inclusion criteria
Participants will include 30 adolescent females with AN (restricting sub-type) (age: 12-19 years) admitted to the Departments of Adolescent Medicine at the CHW and Westmead Hospital, as well as 30 healthy-weight (BMI between 25th and 75th percentiles), aged-matched adolescent female controls. Potential AN participants will meet the diagnosis of anorexia nervosa as per the Diagnostic and Statistical Manual of Mental Health Disorders (4th edition) criteria, and will only be studied once medically stable (i.e. Heart rate >50bpm overnight). Adolescent females must have also reached Tanner stage 3 of development.
Minimum age
12 Years
Maximum age
19 Years
Gender
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1) significant GI disease or previous surgery
2) current medical instability
3) current use of any medications which may affect GI function, weight or appetite
4) diabetes mellitus
5) epilepsy
6) pre-existing cardiovascular/respiratory disease
7) any other significant illness as assessed by the investigator
8) pregnancy or lactation
9) current use of contraceptive medication (e.g. Depo-Provera, Norplant, hormone releasing IUD’s)
11) intake of > 20 g alcohol per day
12) smokers (cigarettes, cigars, marijuana)
13) donation of blood in the 12 weeks prior to enrolment in the study, and participants will also be instructed to abstain from donating blood for 12 weeks after study completion.
14) high performance athletes
15) unable to comprehend study protocol
16) participation in any other research project within the last 3 months
18) abnormal liver function tests
19) have iron or haemoglobin levels below the normal range, as assessed with a screening blood test on admission, and in the week prior to each study day, conducted as part of routine clinical care.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
With regards to gastrointestinal function, we focused on two key parameters in our power calculations: upper gastric motor function (gastric emptying), which is known to respond very quickly to changes in energy intake, and PYY, to represent gastrointestinal hormone function, with research suggesting this is a major factor regulating energy intake. Currently, there is little research investigating the other related gastrointestinal hormones. Between-group comparisons of patients and controls on gastric emptying half-time and PYY concentrations at t = 120 minutes after nutrient ingestion were used in the power calculations. These were selected due to the availability of published data to estimate the magnitude of the differences expected and the amount of variation (estimated standard deviations) for both patients and controls, although the published literature does not provide adequate precedents for the effects of refeeding on gastric hormone release and gastric emptying. As we hypothesise that these values will return to control/healthy levels after refeeding, we expect that our power calculations between patients and controls would allow such an effect from refeeding to be seen.

Calculations were based on between-group comparisons between patients and controls, using the formula for a two-sample t-test at 5% significance level and 80% power. Using estimates of the expected variation in outcomes from previous studies, the detectable difference between groups was calculated for a range of sample sizes to assess the feasibility of the study. A sample size of 30 per group was shown to be adequately powered for both gastric emptying (difference in GE half time 28.3 min) and PYY concentration (difference in PYY at 120 min of 13.8 mmol/L). While there are no reference ranges for these outcome variables in the anorexic population, nor are they used as clinical markers, we believe, based on results in other patient and healthy populations, that these effect sizes are likely to be of clinical relevance.

Data will be analysed statistically using repeated measures ANOVAs to compare variables across time points on each study day and independent samples t-tests to compare the AN and healthy control groups. Repeated measures ANOVAs will also be used to compare variables in AN patients across the three study days in the refeeding period. Post-hoc paired comparisons, corrected for multiple comparisons, will be performed if ANOVAs reveal significant effects. Statistical significance will be accepted at P < 0.05.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment postcode(s) [1] 12691 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 292809 0
Hospital
Name [1] 292809 0
Royal Adelaide Hospital Research Fund
Address [1] 292809 0
North Terrace, Adelaide SA 5000
Country [1] 292809 0
Australia
Primary sponsor type
University
Name
University of Adelaide
Address
Discipline of Medicine
University of Adelaide
Lvl 6 Eleanor Harrald Building
North Terrace
Adelaide SA 5000
Country
Australia
Secondary sponsor category [1] 291547 0
Hospital
Name [1] 291547 0
Royal Adelaide Hospital
Address [1] 291547 0
Discipline of Medicine
Lvl 6 Eleanor Harrald Building
North Terrace
Adelaide SA 5000
Country [1] 291547 0
Australia
Secondary sponsor category [2] 291548 0
Hospital
Name [2] 291548 0
The Children's Hospital at Westmead
Address [2] 291548 0
Adolescent Medicine
Cnr Hawkesbury Road and Hainsworth Street
Westmead 2145 NSW
Country [2] 291548 0
Australia
Other collaborator category [1] 278800 0
Hospital
Name [1] 278800 0
Westmead Hospital
Address [1] 278800 0
Adolescent Medicine
Westmead Hospital
Westmead 2145 NSW
Country [1] 278800 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294309 0
Sydney Children's Hospitals Network Human Research Ethics Committee
Ethics committee address [1] 294309 0
Locked Bag 4001
Westmead NSW 2145
Ethics committee country [1] 294309 0
Australia
Date submitted for ethics approval [1] 294309 0
23/05/2011
Approval date [1] 294309 0
26/09/2011
Ethics approval number [1] 294309 0
11/CHW/88
Ethics committee name [2] 294310 0
Royal Adelaide Hospital Research Ethics Committee
Ethics committee address [2] 294310 0
Royal Adelaide Hosital
North Terrace
Adelaide SA 5000
Ethics committee country [2] 294310 0
Australia
Date submitted for ethics approval [2] 294310 0
02/11/2011
Approval date [2] 294310 0
18/11/2011
Ethics approval number [2] 294310 0
111021

Summary
Brief summary
We propose a comprehensive investigation of the effects of a standardised, intensive refeeding regime on GI function in adolescent patients with restrictive AN, which will form the fundamental basis for subsequent acute investigative and longer-term intervention studies. The study aims to examine whether gastrointestinal (GI) hormone and appetite responses to, and gastric emptying of, a mixed-nutrient oral test meal in anorexia nervosa (AN) patients are modified in response to changes in nutrient exposure and energy expenditure occurring during the refeeding period. Thirty adolescent participants with AN (age 12-19 years) will be recruited during their inpatient admission at the Children’s Hospital at Westmead and Westmead Hospital. They will be studied on 3 separate occasions during their nutritional rehabilitation, and their results compared to thirty age-matched healthy-weight adolescent control participants assessed on one occasion. On each study day, participants in both the AN and control groups will undergo indirect calorimetry to assess energy expenditure. After this, they will receive an oral test meal, following which, GI hormones and appetite perceptions will be measured. Gastric emptying will also be measured on all study days.
Specific hypotheses: (1) In comparison with healthy, age-matched controls, adolescents with AN will have exaggerated ‘anorexigenic’ gut hormone secretion and delayed gastric emptying in response to an intragastric mixed-nutrient test meal. (2) With increased GI nutrient exposure during refeeding over 2 weeks, gut hormone concentrations, blood glucose and gastric emptying will return towards healthy levels. Outcome measures: Gut hormone concentrations, gastric emptying, appetite perceptions, blood glucose, GI symptoms.
Study implications: GI hormone, blood glucose and gastric emptying disturbances in AN will be comprehensively characterised before, during and after treatment, identifying possible GI mechanisms underlying the starvation condition and potential treatment interventions.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 63250 0
Prof Christine Feinle-Bisset
Address 63250 0
Discipline of Medicine
University of Adelaide
Lvl 6 Eleanor Harrald Building
North Terrace
Adelaide SA 5000
Country 63250 0
Australia
Phone 63250 0
+61882225247
Fax 63250 0
+6188223 3870
Email 63250 0
christine.feinle@adelaide.edu.au
Contact person for public queries
Name 63251 0
Ms Gabriella Heruc
Address 63251 0
Discipline of Medicine
University of Adelaide
Lvl 6 Eleanor Harrald Building
North Terrace
Adelaide SA 5000
Country 63251 0
Australia
Phone 63251 0
+61411770111
Fax 63251 0
+6188223 3870
Email 63251 0
gabriella.heruc@adelaide.edu.au
Contact person for scientific queries
Name 63252 0
Ms Gabriella Heruc
Address 63252 0
Discipline of Medicine
University of Adelaide
Lvl 6 Eleanor Harrald Building
North Terrace
Adelaide SA 5000
Country 63252 0
Australia
Phone 63252 0
+61411770111
Fax 63252 0
+6188223 3870
Email 63252 0
gabriella.heruc@adelaide.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary