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Trial registered on ANZCTR


Registration number
ACTRN12622001190796
Ethics application status
Approved
Date submitted
19/08/2022
Date registered
6/09/2022
Date last updated
13/02/2023
Date data sharing statement initially provided
6/09/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigating the effect of continuous theta burst stimulation (cTBS) on the brain's response to food cues in adults with obesity: a pilot study
Scientific title
A pilot study of continuous theta burst stimulation to modulate neural functional connectivity underpinning food craving in adults with obesity
Secondary ID [1] 307760 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obesity 327333 0
Food cravings 327334 0
Condition category
Condition code
Diet and Nutrition 324465 324465 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A single-blind, active sham-controlled cross-over design will be used. Participants will undertake two experimental sessions based at the Monash Biomedical Imaging facility, with a six-to-eight day washout period separating these sessions. During each session, participants will receive a single session of continuous theta burst stimulation, a form of non-invasive repetitive transcranial magnetic stimulation (cTBS-rTMS). In each session, participants will either receive real cTBS (active condition, 45 minute session) or placebo cTBS (sham condition, 45 minute session), with the order of these conditions randomised across participants.

Continuous theta burst stimulation will be administered using a figure-of-eight Cool-B65 A/P coil attached to a MagVenture MagPro X100 stimulator (MagVenture, Farum, Denmark). A neuronavigation system will be used to monitor coil placement and personalise the stimulation site based on inter-individual morphological differences (Brainsight, Rogue Research). Resting motor threshold (RMT) will be computed as the minimum stimulator intensity required to evoke a motor evoked potential on 50% of trials from a contralateral hand muscle when stimulating the primary motor cortex.

Stimulation will be applied to the left medial prefrontal cortex, using the left frontal pole (Fp1) coordinates detailed in Scrivener et al. (2022) (MNI coordinates: x = -24.54, y = 66.41, z = 11.97) to guide positioning of the coil. Participants will receive two trains of continuous theta burst stimulation over this site, separated by a 10 minute inter-train interval (one train = 40 s; three pulse bursts at 50 Hz repeated at 5 Hz; 600 pulses/train). Stimulation intensity will be set to 70% RMT for each participant, adjusted for scalp-to-cortex distance.

Both sessions of rTMS-cTBS will be administered by research staff accredited to operate rTMS-cTBS and who hold a current Provide First Aid certificate. Participants’ adherence to the intervention (i.e., attendance of both sessions) will be recorded using a session attendance form. To assess unintended effects of rTMS-cTBS and awareness of sham/active condition, participants will complete Section IV of the TMSens_Q (Giustiniani et al., 2022).

Immediately before and after the stimulation procedure, participants will also receive functional magnetic resonance imaging (fMRI). Specifically, participants will undergo a pre-stimulation scan (45 minutes) and a post-stimulation scan (45 minutes) in each session. During this scan, participants will complete an fMRI compatible food go/no-go task (adapted from He et al., 2015).

Giustiniani, A., et al. A questionnaire to collect unintended effects of Transcranial Magnetic Stimulation: A consensus based approach. Clinical Neurophysiology (2022). https://doi.org/10.1016/j.clinph.2022.06.008

He, Q., Xiao, L., Xue, G. et al. Poor ability to resist tempting calorie rich food is linked to altered balance between neural systems involved in urge and self-control. Nutr J 13, 92 (2014). https://doi.org/10.1186/1475-2891-13-92
Intervention code [1] 324224 0
Treatment: Devices
Comparator / control treatment
Sham or placebo continuous theta burst stimulation: The sham intervention will use the same device and procedures as the active intervention, but with the coil flipped so that the placebo side is facing the scalp and no stimulation is applied. Skin surface electrodes will be placed on the participant's forehead around the stimulation site, to simulate the sensations of active stimulation. A condition check survey will be administered to participants following their second session, to assess whether they were able to tell the difference between the active and sham protocols.
Control group
Placebo

Outcomes
Primary outcome [1] 332271 0
Food go/no-go task evoked changes in brain functional connectivity indicated by functional magnetic resonance imaging (fMRI). The food go/no-go task (He et al., 2015) involves the rapid presentation of a series of visual food stimuli, and participants are asked to enact (“go”) or inhibit (“no-go”) motor responses in response to these stimuli. fMRI functional connectivity analyses will measure signal covariance between the medial prefrontal cortex (the site of the stimulation) and the rest of the brain while participants engage in the food go/no-go task.

He, Q., Xiao, L., Xue, G. et al. Poor ability to resist tempting calorie rich food is linked to altered balance between neural systems involved in urge and self-control. Nutr J 13, 92 (2014). https://doi.org/10.1186/1475-2891-13-92
Timepoint [1] 332271 0
Task-related functional connectivity data will be collected during a magnetic resonance imaging scan held immediately before and after each continuous theta burst stimulation session (active and sham).
Primary outcome [2] 332272 0
Food go/no-go task evoked changes in brain functional activation indicated by functional magnetic resonance imaging (fMRI).
Timepoint [2] 332272 0
Task-related activation data will be collected during a magnetic resonance imaging (MRI) scan held immediately before and after each continuous theta burst stimulation session (active and sham).
Primary outcome [3] 332273 0
The subjective intensity of food cravings will be measured using a 10-point, single-item, visual analogue scale, with responses ranging from "1" (no craving) to "10" (high craving).
Timepoint [3] 332273 0
The visual analogue scale will be administered at four timepoints during each experimental session: (1) at baseline (prior to resting motor thresholding), (2) immediately following the first MRI scan, (3) immediately following cTBS, and (4) immediately following the second MRI scan.
Secondary outcome [1] 412780 0
Changes in food cravings, assessed using an ecological momentary assessment survey hosted on the smartphone application, SEMA3.
Timepoint [1] 412780 0
Participants will complete the ecological momentary assessment survey at three timepoints following each session: (1) during the afternoon following the session, (2) during the evening on the day of the session, and (3) during the next morning after the session.
Secondary outcome [2] 412783 0
Changes in behavioural responses on the food go/no-go task (i.e., response inhibition and habitual responding towards high- or low-calorie food images).
Timepoint [2] 412783 0
This task will be completed in the MRI scanner immediately before and after each continuous theta burst stimulation session (active and sham).

Eligibility
Key inclusion criteria
• Aged between 18 and 55 years old
• Body mass index (BMI) equal to or exceeding 30 kg/m2
• Able to read and converse in English
• Weigh less than 200 kg
• No current diagnosis of neurological, endocrine, or metabolic disorder affecting brain function
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Body weight of more than 200 kg
• Contraindications to brain stimulation identified by the TMS safety screening form, a history of seizures, frequent migraine headaches, or any other diagnosed neurological, endocrine, or metabolic condition affecting brain function
• Diagnosis of schizophrenia or psychosis
• MRI contraindications indicated by MRI screening procedures
• Currently pregnant or breastfeeding
• No smartphone device

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)
Treatment allocation concealment will be achieved by using a password-protected computer program, implemented by a member of the research team who will inform the principal investigator of the outcome via email. The person who will determine the eligibility of the participants will be unaware of which stimulation will be given in each of the two treatment weeks.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e., computerised sequence generation).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
20/10/2022
Actual
20/10/2022
Date of last participant enrolment
Anticipated
12/09/2023
Actual
20/01/2023
Date of last data collection
Anticipated
23/09/2023
Actual
27/01/2023
Sample size
Target
20
Accrual to date
Final
10
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 312068 0
Other Collaborative groups
Name [1] 312068 0
Turner Institute for Brain and Mental Health
Country [1] 312068 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Turner Institute for Brain and Mental Health
Address
Turner Institute for Brain and Mental Health
Monash University
Level 5, 18 Innovation Walk
Clayton VIC 3800
Country
Australia
Secondary sponsor category [1] 313526 0
None
Name [1] 313526 0
Address [1] 313526 0
Country [1] 313526 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311445 0
Monash University Human Research Ethics Committee
Ethics committee address [1] 311445 0
Monash University
Wellington Rd
Clayton VIC 3800
Ethics committee country [1] 311445 0
Australia
Date submitted for ethics approval [1] 311445 0
Approval date [1] 311445 0
16/08/2022
Ethics approval number [1] 311445 0

Summary
Brief summary
Obesity is a leading contributor to preventable mortality in Australia. While the causes of obesity are multifaceted, epidemiological studies suggest that overconsumption of highly rewarding energy-dense and ultra-processed food is a leading driver of rising obesity rates. Our team has previously shown that obesity is associated with abnormal communication between the brain regions involved in reward responses to food (i.e., the medial prefrontal cortex [mPFC], striatum and insula), and those involved in energy regulation (i.e., the hypothalamus). These regions and their connections have also been linked to food cravings which are a known driver of overconsumption. Therefore, interventions that can modulate neural connectivity between cortico-striatal-hypothalamic regions are promising candidates to reduce food cravings in people with obesity. The connectivity between these brain regions can be modulated using non-invasive brain stimulation, namely a form of repetitive transcranial magnetic stimulation (rTMS) known as continuous theta burst stimulation (cTBS). rTMS is an FDA approved treatment for depression and is being trialled for multiple psychiatric and neurodegenerative diseases. In this trial we will test if rTMS-cTBS can reduce abnormally increased connections between brain regions involved in food reward responses in obesity. We expect that rTMS-cTBS over the mPFC will reduce abnormally increased connectivity (i.e. neural communication) between the mPFC and regions of the brain reward circuit involved in food cravings.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 121118 0
Prof Antonio Verdejo-García
Address 121118 0
Turner Institute for Brain and Mental Health
Monash University
Level 5, 18 Innovation Walk
Clayton VIC 3800
Country 121118 0
Australia
Phone 121118 0
+61 3 9905 5374
Fax 121118 0
Email 121118 0
[email protected]
Contact person for public queries
Name 121119 0
Antonio Verdejo-García
Address 121119 0
Turner Institute for Brain and Mental Health
Monash University
Level 5, 18 Innovation Walk
Clayton VIC 3800
Country 121119 0
Australia
Phone 121119 0
+61 3 9905 5374
Fax 121119 0
Email 121119 0
[email protected]
Contact person for scientific queries
Name 121120 0
Antonio Verdejo-García
Address 121120 0
Turner Institute for Brain and Mental Health
Monash University
Level 5, 18 Innovation Walk
Clayton VIC 3800
Country 121120 0
Australia
Phone 121120 0
+61 3 9905 5374
Fax 121120 0
Email 121120 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
Consent not obtained for this use.


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.