Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000731493
Ethics application status
Approved
Date submitted
16/06/2025
Date registered
8/07/2025
Date last updated
8/07/2025
Date data sharing statement initially provided
8/07/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Gaining a Holistic Understanding of Eating Disorders: Phenotyping and Genotyping Illness
Scientific title
Gaining a Holistic Understanding of Eating Disorders: Phenotyping and Genotyping Illness
Secondary ID [1] 314387 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Eating Disorders 337392 0
Condition category
Condition code
Mental Health 333768 333768 0 0
Eating disorders

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
The Holistic Understanding Study is a longitudinal, multi-site, biopsychosocial phenotyping and genotyping study designed to clarify the multi-level mechanisms underpinning eating disorders (EDs), including Anorexia Nervosa (AN), Bulimia Nervosa (BN), Binge Eating Disorder (BED), Avoidant/Restrictive Food Intake Disorder (ARFID), and Other Specified Feeding or Eating Disorder (OSFED). The rationale is grounded in the limited effectiveness of current evidence-based treatments and high relapse rates, suggesting that existing models insufficiently capture the complexity of EDs. This study seeks to generate a comprehensive and integrated understanding of illness trajectory, driving and maintenance mechanisms, and individual treatment targets by collecting extensive behavioural, cognitive, neurobiological, genomic, and psychosocial data.

Participants aged 14 years and older are recruited through national ED networks, clinical services, and digital platforms. Following screening, eligible participants complete a structured assessment protocol across four timepoints: baseline (T1), 12 weeks (T2), 26 weeks (T3), and 52 weeks (T4). There will be 4 assessments conducted on separate days and completed within 7 days: (1) a two-hour online psychometric survey administered via REDCap comprising validated measures of ED symptomatology, identity, quality of life, psychopathology, and interoception, and The Self-Referential Memory Paradigm and the Connectedness: Sense of Commitment Paradigm tasks administered via Qualtrics hosted by The University of Sydney; (2) a 2 hour and 40-minute semi-structured clinical interview via Zoom, including the Eating Disorder Examination (EDE) with EDE ARFID module, Mini International Neuropsychiatric Interview (MINI), and Occupational Performance History Interview; (3) a 1.5-hour online psychometric survey administered via REDCap comprising validated measures of impulsivity, emotion regulation, and social cognition, and a Cognitive Impulsivity Suite administered via an existing platform hosted by Monash University of gamified assessment of three constructs important for understanding different processes underlying cognitive impulsivity including attentional control, information gathering, and monitoring/shifting; and (4) a three-hour in-person assessment involving collection of biological samples (blood, faeces), anthropometric and physiological measurements (weight, height, blood pressure), functional and structural MRI (including a food-choice task). Participants will be asked to wear a smart watch to measure sleep, activity, heart rate, and stress for 26 weeks.

A total 420 ‘full participants’ will complete assessments 1-4. This cohort will be selected to ensure a representative range of eating disorder diagnostic categories: Anorexia Nervosa (AN) – 56, Bulimia Nervosa (BN) – 102, Binge Eating Disorder (BED) – 102, Avoidant/Restrictive Food Intake Disorder (ARFID) – 30, Anorexia Nervosa in adults (AN adult) – 30, and Other Specified Feeding or Eating Disorder (OSFED) including Atypical Anorexia Nervosa (Atypical AN) – 100. Participants must be ‘full participants’ of the Holistic Understanding study to be eligible for a companion clinical trial for AN, OSFED Atypical AN, BN or BED. Eligible participants will be offered enrolment in a companion clinical trial. A total 256 ‘partial participants’ will complete assessment 1-3 only. Additional ‘eCohort participants’ beyond the minimum target of 676 will complete an abbreviated form of the study that is available fully online, including assessments 1 and 2 only. A modified assessment protocol will be implemented at T1, T2, T3 and T4 depending on the timepoint and whether the participant is a full, partial or eCohort participant.

All assessments are standardised and delivered individually via a hybrid model: online (REDCap), remote (Zoom/telephone), and in-person across three academic and clinical sites in NSW and Victoria. Research staff conducting interviews and sample collection are trained in assessment delivery, risk management, and biosafety procedures. Biological samples are stored and processed at a central laboratory, with blood analysed for hormonal, metabolic and inflammatory markers, and genomic data used for genomic wide association studies (GWAS) and polygenic risk score estimation. MRI data are collected using a 3T Siemens Prisma scanner and include structural, resting-state, and task-based fMRI sequences.

Data from this study will inform precision medicine approaches by enabling multivariate modelling (e.g., cluster analysis, network modelling) of latent traits and illness subtypes across ED diagnoses. The study also supports companion clinical trials by providing a detailed characterisation of participants for personalised treatment allocation, and exploration of mechanisms of change. The companion clinical trials (not covered in this registration form) include 1) A Sequential Multiple Assignment Randomised Trial (SMART) of personalised treatment for Bulimia Nervosa and Binge Eating Disorder (protocol number: X24-0273), and 2) For Me Trial: A Pragmatic N-of-1 Multiple Baseline Single-Case Experimental Design (SCED) Study to Evaluate a Personalised Package of Care for Young People with Anorexia Nervosa and their Carers (protocol number: X24-0243).
Intervention code [1] 330998 0
Not applicable
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 341350 0
Eating disorder symptoms
Timepoint [1] 341350 0
Baseline (T1), 12 weeks (T2), 26 weeks (T3), 52 weeks (T4) post-enrolment.
Primary outcome [2] 341351 0
Severity of binge eating
Timepoint [2] 341351 0
Baseline (T1), 12 weeks (T2), 26 weeks (T3), 52 weeks (T4) post -enrolment.
Primary outcome [3] 341352 0
Psychopathology symptoms
Timepoint [3] 341352 0
Baseline (T1), and 52 weeks (T4) post-enrolment.
Secondary outcome [1] 447230 0
Obsessive-compulsive symptoms
Timepoint [1] 447230 0
Baseline (T1), 12 weeks (T2), 26 weeks (T3), 52 weeks (T4) post-enrolment.
Secondary outcome [2] 447232 0
Eating disorder recovery
Timepoint [2] 447232 0
Baseline (T1), 12 weeks (T2), 26 weeks (T3), 52 weeks (T4) post-enrolment.
Secondary outcome [3] 447233 0
Perception of teasing
Timepoint [3] 447233 0
Baseline (T1), 12 weeks (T2), 26 weeks (T3), 52 weeks (T4) post-enrolment.
Secondary outcome [4] 447234 0
Self-concept and identity
Timepoint [4] 447234 0
Baseline (T1), 12 weeks (T2), 26 weeks (T3), 52 weeks (T4) post-enrolment.
Secondary outcome [5] 447235 0
Quality of life.
Timepoint [5] 447235 0
Baseline (T1), 12 weeks (T2), 26 weeks (T3), 52 weeks (T4) post-enrolment.
Secondary outcome [6] 447236 0
Autism symptoms
Timepoint [6] 447236 0
Baseline (T1), 12 weeks (T2), 26 weeks (T3), 52 weeks (T4) post-enrolment.
Secondary outcome [7] 447237 0
Interceptive awareness
Timepoint [7] 447237 0
Baseline (T1), 12 weeks (T2), 26 weeks (T3), 52 weeks (T4) post-enrolment.
Secondary outcome [8] 447238 0
Flexibility of eating disorder patterns
Timepoint [8] 447238 0
Baseline (T1), 12 weeks (T2), 26 weeks (T3), 52 weeks (T4) post-enrolment.
Secondary outcome [9] 447239 0
Perception of connectedness
Timepoint [9] 447239 0
Baseline (T1), 12 weeks (T2), 26 weeks (T3), 52 weeks (T4) post-enrolment.
Secondary outcome [10] 447240 0
Identity traits for eating disorders
Timepoint [10] 447240 0
Baseline (T1), 12 weeks (T2), 26 weeks (T3), 52 weeks (T4) post-enrolment.
Secondary outcome [11] 447241 0
Social determinants of health
Timepoint [11] 447241 0
Baseline (T1), 12 weeks (T2), 26 weeks (T3), 52 weeks (T4) post-enrolment.
Secondary outcome [12] 447242 0
Food insecurity
Timepoint [12] 447242 0
Baseline (T1), and 52 weeks (T4) post-enrolment.
Secondary outcome [13] 447243 0
Body image
Timepoint [13] 447243 0
Baseline (T1), 12 weeks (T2), 26 weeks (T3), 52 weeks (T4) post-enrolment.
Secondary outcome [14] 447244 0
Personality traits
Timepoint [14] 447244 0
Baseline (T1), 12 weeks (T2), 26 weeks (T3), 52 weeks (T4) post-enrolment.
Secondary outcome [15] 447245 0
Emotional functioning
Timepoint [15] 447245 0
Baseline (T1), 12 weeks (T2), 26 weeks (T3), 52 weeks (T4) post-enrolment.
Secondary outcome [16] 447246 0
Motivation to change
Timepoint [16] 447246 0
Baseline (T1), 12 weeks (T2), 26 weeks (T3), 52 weeks (T4) post-enrolment.
Secondary outcome [17] 447248 0
Occupational performance
Timepoint [17] 447248 0
Baseline (T1) and 26 weeks (T3) post-enrolment.
Secondary outcome [18] 447250 0
Sensory processing
Timepoint [18] 447250 0
Baseline (T1), 26 weeks (T3) post-enrolment.
Secondary outcome [19] 447251 0
Self-referential memory
Timepoint [19] 447251 0
Baseline (T1), 26 weeks (T3) post-enrolment.
Secondary outcome [20] 447252 0
Connectedness and commitment
Timepoint [20] 447252 0
Baseline (T1), 26 weeks (T3) post-enrolment.
Secondary outcome [21] 447253 0
Cognitive impulsivity
Timepoint [21] 447253 0
Baseline (T1), 26 weeks (T3) post-enrolment.
Secondary outcome [22] 447254 0
Fear of food
Timepoint [22] 447254 0
Baseline (T1), 12 weeks (T2), 26 weeks (T3), 52 weeks (T4) post-enrolment.
Secondary outcome [23] 447255 0
Impulsivity
Timepoint [23] 447255 0
Baseline (T1), 12 weeks (T2), 26 weeks (T3), 52 weeks (T4) post-enrolment.
Secondary outcome [24] 447256 0
Interpersonal problems
Timepoint [24] 447256 0
Baseline (T1), 12 weeks (T2), 26 weeks (T3), 52 weeks (T4) post-enrolment.
Secondary outcome [25] 447257 0
Emotion regulation
Timepoint [25] 447257 0
Baseline (T1), 12 weeks (T2), 26 weeks (T3), 52 weeks (T4) post-enrolment.
Secondary outcome [26] 447258 0
Avoidance tendencies
Timepoint [26] 447258 0
Baseline (T1), 12 weeks (T2), 26 weeks (T3), 52 weeks (T4) post-enrolment.
Secondary outcome [27] 447261 0
Readiness and motivation to change
Timepoint [27] 447261 0
Baseline (T1), 12 weeks (T2), 26 weeks (T3), 52 weeks (T4) post-enrolment.
Secondary outcome [28] 447263 0
Attachment
Timepoint [28] 447263 0
Baseline (T1), 12 weeks (T2), 26 weeks (T3), 52 weeks (T4) post-enrolment.
Secondary outcome [29] 447264 0
Early maladaptive thoughts and behaviours.
Timepoint [29] 447264 0
Baseline (T1), 12 weeks (T2), 26 weeks (T3), 52 weeks (T4) post-enrolment.
Secondary outcome [30] 447265 0
Genetic and metabolic assessment
Timepoint [30] 447265 0
Baseline (T1), 26 weeks (T3) post-enrolment.
Secondary outcome [31] 447266 0
Gut microbiota assessment
Timepoint [31] 447266 0
Baseline (T1), week 12 (T2) and 26 weeks (T3) post-enrolment.
Secondary outcome [32] 449073 0
Decision making
Timepoint [32] 449073 0
Baseline (T1), 26 weeks (T3) post-enrolment.
Secondary outcome [33] 449077 0
Decision making
Timepoint [33] 449077 0
Baseline (T1), 26 weeks (T3) post-enrolment.
Secondary outcome [34] 449078 0
Activity
Timepoint [34] 449078 0
Daily from baseline (T1) to 26 weeks (T3) post-enrolment.
Secondary outcome [35] 449079 0
Sleep
Timepoint [35] 449079 0
Smart watch
Secondary outcome [36] 449080 0
Heart rate and stress
Timepoint [36] 449080 0
Daily from baseline (T1) to 26 weeks (T3) post-enrolment.
Secondary outcome [37] 449093 0
Neurological assessment
Timepoint [37] 449093 0
Baseline (T1), 26 weeks (T3) post-enrolment.
Secondary outcome [38] 449094 0
Neurological assessment
Timepoint [38] 449094 0
Baseline (T1), 26 weeks (T3) post-enrolment.
Secondary outcome [39] 449095 0
Neurological assessment
Timepoint [39] 449095 0
Baseline (T1), 26 weeks (T3) post-enrolment.

Eligibility
Key inclusion criteria
1. Aged 14 years and older
2. English speaking and reading proficiency
3. Computer literacy skills
4. Satisfies DSM-5 criteria for a threshold ED (i.e., AN, BN, BED, ARFID, OSFED) or subthreshold ED
5. Willing and able to comply with all study requirements, including timing and/or nature of required assessments
Minimum age
14 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Active suicidality
2. Active psychosis
3. Pregnant

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
A target sample size of 676 participants is required to ensure adequate power for network analysis involving up to 50 nodes. All 676 will complete the full psychometric, clinical interview and cognitive testing assessment time points, with 420 participants, representative of the range of eating disorder diagnostic categories, also completing neuroimaging, additional cognitive testing and biospecimen collection. Additional participants beyond the minimum of 676 will be able to participate in an abbreviated form of the psychometric and cognitive testing that is available fully online, to extend and add to the representativeness of the sample.

Descriptive statistics will be reported for all variables measured. Statistical comparison such as ANOVA and Chi-square tests will be carried out to explore and compare background participant and sites-related characteristics. Self-reported, clinical and biological information obtained will be explored and analysed using regressions, bivariate and canonical correlations, multi-view cluster and profile analyses and network modelling. Neuroimaging data will be analysed using network-based modelling and task-based analyses, such as statistical parametric mapping. Longitudinal data will be analysed using mixed-effects repeated measures models. Statistical software (RStudio, STATA, MATLAB, and SPSS) will be used for the statistical analysis.

Semi-structured clinical interviews will be transcribed verbatim by the researchers and analysed using Interpretative Phenomenological Analysis (IPA).

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
15/07/2025
Actual
Date of last participant enrolment
Anticipated
1/07/2027
Actual
Date of last data collection
Anticipated
1/07/2028
Actual
Sample size
Target
676
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 27997 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 27998 0
Monash University - School of Psychological Sciences - Clayton
Recruitment hospital [3] 27999 0
La Trobe University - School of Psychology and Public Health - Albury-Wodonga Campus - West Wodonga
Recruitment postcode(s) [1] 44199 0
2050 - Camperdown
Recruitment postcode(s) [2] 44200 0
3168 - Clayton
Recruitment postcode(s) [3] 44201 0
3690 - West Wodonga

Funding & Sponsors
Funding source category [1] 318907 0
Government body
Name [1] 318907 0
Commonwealth Department of Health National Leadership in Mental Health Program Grant ID P051002 - 4G0TT7NX
Country [1] 318907 0
Australia
Funding source category [2] 319154 0
Other Collaborative groups
Name [2] 319154 0
Australian Eating Disorders Research and Translation Centre
Country [2] 319154 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
Country
Australia
Secondary sponsor category [1] 321368 0
Hospital
Name [1] 321368 0
Sydney Local Health DIstrict
Address [1] 321368 0
Country [1] 321368 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 317521 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 317521 0
Ethics committee country [1] 317521 0
Australia
Date submitted for ethics approval [1] 317521 0
18/06/2024
Approval date [1] 317521 0
27/06/2025
Ethics approval number [1] 317521 0
Protocol No. X24-0167 & 2024/ETH01105

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

Contacts
Principal investigator
Name 141310 0
Prof Sarah Maguire
Address 141310 0
The University of Sydney, Level 2, The Charles Perkins Centre, D17 Johns Hopkins Dr, Camperdown NSW 2050
Country 141310 0
Australia
Phone 141310 0
+61 2 86271910
Fax 141310 0
Email 141310 0
[email protected]
Contact person for public queries
Name 141311 0
Project Manager
Address 141311 0
The University of Sydney, Level 2, The Charles Perkins Centre, D17 Johns Hopkins Dr, Camperdown NSW 2050
Country 141311 0
Australia
Phone 141311 0
+61 2 8627 5690
Fax 141311 0
Email 141311 0
[email protected]
Contact person for scientific queries
Name 141312 0
Project Manager
Address 141312 0
The University of Sydney, Level 2, The Charles Perkins Centre, D17 Johns Hopkins Dr, Camperdown NSW 2050
Country 141312 0
Australia
Phone 141312 0
+61 2 8627 5690
Fax 141312 0
Email 141312 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
Yes
Will there be any conditions when requesting access to individual participant data?
Persons/groups eligible to request access:
• Data are potentially available to:
- Researchers from not-for-profit organisations
- Commercial Organisations
- Other

Based in:
- Any location

Conditions for requesting access:
• All data requests will be considered by the primary sponsor on a case-by-case basis. Requests must include a methodologically sound proposal. Specific conditions of use may apply and will be specified in a data sharing agreement (or similar) that the requester must agree to before access is granted. For further information please contact [email protected].

What individual participant data might be shared?
• All de-identified individual participant data
What types of analyses could be done with individual participant data?
• Any type of analysis, and will be assessed on a case-by-case basis

When can requests for individual participant data be made (start and end dates)?
From:
After publication of main results
To:
No end date
Where can requests to access individual participant data be made, or data be obtained directly?
• Email of trial custodian, sponsor or committee: Please contact the Signature Studies team at [email protected]

Are there extra considerations when requesting access to individual participant data?
No


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.