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Trial registered on ANZCTR


Registration number
ACTRN12618000623291
Ethics application status
Approved
Date submitted
17/04/2018
Date registered
20/04/2018
Date last updated
16/07/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Neural mechanisms of lisdexamfetamine in binge eating disorder.
Scientific title
Understanding the neural mechanisms of Lisdexamfetamine dimesylate (LDX) pharmacotherapy in binge-eating disorder.
Secondary ID [1] 294610 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Binge-Eating Disorder 307442 0
Condition category
Condition code
Mental Health 306528 306528 0 0
Eating disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Drug name: Lisdexamfetamine dimesylate
Mode of administration: oral tablet
Dose and duration of administration: Intervention is planned to be titrated. All binge-eating disorder patients will commence with 30mg once daily for 2 weeks, then increase to 50mg once daily for the next 2 weeks following a blood pressure check. At 4-weeks, all participants will receive a safety and dose check by a study clinician. The clinician will assess whether those responsive to the medication should maintain their dose of 50mg once daily for the next 4 weeks, or whether those non-responsive should increase their dose to 70mg once daily for the next 4 weeks.

Strategies used to monitor adherence to the intervention will include:
- Participant diary to be completed daily, including a checkbox for medication compliance.
- Participants will be required to return all medication blister packs (used or unused) at the follow-up session, which will be counted for compliance rate. If less than 60% of tablets have been taken at this point, this will be viewed as non-compliant.
Intervention code [1] 300913 0
Treatment: Drugs
Intervention code [2] 300914 0
Behaviour
Comparator / control treatment
The comparator/control group against which the study intervention is being compared will receive no treatment. This group will consist of healthy participants who are recruited separately from BED patients, and are matched with BED patients on age, gender and BMI.
Control group
Active

Outcomes
Primary outcome [1] 305535 0
Changes in resting-state functional connectivity between reward and inhibition networks in participants on LDX after 8 weeks of treatment, relative to pre-treatment, as assessed by MRI scans.
Timepoint [1] 305535 0
Baseline; 8 weeks after LDX treatment commencement.
Primary outcome [2] 305563 0
Changes in resting-state functional connectivity between reward and inhibition networks in participants on LDX after 8 weeks of treatment, relative to no-treatment controls, as assessed by MRI scans.
Timepoint [2] 305563 0
Baseline; 8 weeks after LDX treatment commencement.
Secondary outcome [1] 345645 0
Changes in binge-eating symptoms, as assessed by the number of binge-eating events in the past week in a self-report diary.
Timepoint [1] 345645 0
Baseline; 8 weeks after LDX treatment commencement.
Secondary outcome [2] 345781 0
Changes in functional connectivity between reward and inhibition networks.
Timepoint [2] 345781 0
Baseline; 8 weeks after LDX treatment commencement.

Eligibility
Key inclusion criteria
The key inclusion criteria for BED patients are:
- Age 18 – 40 years.
- Binge-eating disorder diagnosis, confirmed by the eating disorders module of the Structured Clinical Interview for DSM 5.
- Moderate to severe BED, defined as the presence of binge eating frequency of 3 days/week or greater in the month prior to the baseline assessment and a score of 4 or greater on the clinical global impressions severity scale.
- Body mass index of 20 – 45kg/m2.
- A study doctor has verified that it is medically and psychiatrically safe for their patient to commence LDX.
- Fluent in English.
- Have provided written informed consent.

The key inclusion criteria for control participants are:
- Age 18 – 40 years.
- Body Mass Index 20-45 kg/m2.
- Fluent in English.
- Have provided written informed consent.
Minimum age
18 Years
Maximum age
40 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
The key exclusion criteria for BED patients are:
- Current anorexia or bulimia nervosa.
- History of psychosis or mania.
- Pregnant or breast-feeding women.
- Current therapy with antipsychotics or norepinephrine reuptake inhibitors.
- Cardiovascular disease, hypertension, use of monoamine oxidase inhibitors (MAOIs), or any other contraindications for psychostimulants.
- History of substance abuse/dependence (excluding nicotine).
- Previous suicide attempts or current suicidal ideation.
- Known medical condition, disease or neurological disorder which might, in the opinion of investigator/s, interfere with the assessments to be made in the study or put BED patients at increased risk when exposed to optimal doses of the drug treatment. For example, hypertension or a diagnosis of epilepsy would exclude a patient from this trial.
- Use of a psychostimulant in the 6 months prior to the study.
- Inability to tolerate the MRI scanner due to physical or psychological factors.
- History of physical brain injury or blow to the head that resulted in loss of consciousness for at least 10 minutes.

The key exclusion criteria for control participants are:
- Current or previous diagnosis of an eating disorder or any other psychiatric diagnosis, including substance dependence.
- Pregnant or breast-feeding women.
- Inability to tolerate the MRI scanner due to physical or psychological factors.
- Known medical condition, disease or neurological disorder which might, in the opinion of investigator/s, interfere with the assessments to be made in the study or put subjects at increased risk.
- History of physical brain injury or blow to the head that resulted in loss of consciousness for at least 10 minutes.
- Prior treatment with any stimulant medication.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Pharmacodynamics
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
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

Funding & Sponsors
Funding source category [1] 299226 0
Commercial sector/Industry
Name [1] 299226 0
Shire International GmbH
Address [1] 299226 0
Zählerweg 10, CH-6300 Zug
Country [1] 299226 0
Switzerland
Primary sponsor type
University
Name
University of Sydney
Address
Camperdown, NSW, 2006
Country
Australia
Secondary sponsor category [1] 298496 0
None
Name [1] 298496 0
Not applicable
Address [1] 298496 0
Not applicable
Country [1] 298496 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300151 0
Western Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 300151 0
Ethics committee country [1] 300151 0
Australia
Date submitted for ethics approval [1] 300151 0
17/10/2017
Approval date [1] 300151 0
04/05/2018
Ethics approval number [1] 300151 0
AU RED HREC/17/WMEAD490

Summary
Brief summary
While Lisdexamfetamine dimesylate (LDX) is indicated for moderate to severe binge-eating disorder (BED) in Australia, the exact mode of its therapeutic action in BED remains unknown. This study aims to provide a comprehensive understanding of the neural mechanisms by which LDX improves symptoms of BED. We hypothesise that:
1. LDX will act by altering connectivity within and between brain circuits responsible for reward and inhibition.
2. A reduction in binge-eating behaviours will correlate with increased activity and connectivity of brain regions within reward and inhibition circuits.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 82710 0
A/Prof Michael Kohn
Address 82710 0
Department of Adolescent and Young Adult Medicine
Level 2, Westmead Hospital
Hawkesbury Road, Westmead NSW 2137
Country 82710 0
Australia
Phone 82710 0
+61288906788
Fax 82710 0
Email 82710 0
michael.kohn@health.nsw.gov.au
Contact person for public queries
Name 82711 0
Ms Jenny Yang
Address 82711 0
Westmead Institute for Medical Research
176 Hawkesbury Road, Westmead NSW 2145
Country 82711 0
Australia
Phone 82711 0
+61286273321
Fax 82711 0
Email 82711 0
wimr.bedstudy@sydney.edu.au
Contact person for scientific queries
Name 82712 0
Dr Kristi Griffiths
Address 82712 0
Westmead Institute for Medical Research
176 Hawkesbury Road, Westmead NSW 2145
Country 82712 0
Australia
Phone 82712 0
+61286273318
Fax 82712 0
Email 82712 0
kristi.griffiths@sydney.edu.au

No data has been provided for results reporting
Summary results
Not applicable