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Trial registered on ANZCTR


Registration number
ACTRN12624001065583
Ethics application status
Approved
Date submitted
8/08/2024
Date registered
3/09/2024
Date last updated
28/10/2024
Date data sharing statement initially provided
3/09/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised controlled trial to evaluate the effects of marked weight loss combined with exercise training on metabolic, immunological, and imaging biomarkers of systemic and brain inflammation in participants undergoing bariatric surgery.
Scientific title
A randomised controlled trial to evaluate the effects of marked weight loss combined with exercise training on metabolic, immunological, and imaging biomarkers of systemic and brain inflammation in participants undergoing bariatric surgery.
Secondary ID [1] 311727 0
None.
Universal Trial Number (UTN)
Trial acronym
NeuroFit: NEUROlogical Impact of Weight Reduction and FITness Interventions
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obesity 333806 0
Neuroinflammation 333807 0
Condition category
Condition code
Diet and Nutrition 330475 330475 0 0
Obesity
Neurological 330476 330476 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
BARIATRIC SURGERY
Eligible participants will undergo either gastric bypass or gastric sleeve surgery. Either surgery results in calorie restriction and significant weight loss (>20% of body weight). The safety and appropriateness of surgery for each candidate will have been determined by health staff. Following surgery, all participants will be reviewed frequently in the acute post-operative phase by health staff and should they become ineligible for the study, this will be communicated to the research team. Provided no complications, the research team will engage with participants during their routine 6-week follow-up to commence the exercise intervention.

EXERCISE INTERVENTION:
Between weeks 6 and 18, participants will attend a supervised physical activity programme. This programme will be individualised per each participant’s baseline activity and injuries. To measure baseline activity, all participants will wear a Fitbit physical activity tracker for seven continuous days (non-dominant wrist) and will complete a Physical Activity Readiness (PAR) questionnaire prior to their 6-week visit. At this visit, they will also complete a 6-minute walk test, VO2 sub-max test, and undergo a strength assessment with an accredited exercise physiologist (AEP) who will set up a personalised programme.

The goal is for participants to work up to the below physical activity goals during the supervised period:
(1) At least 150 minutes of moderate-intensity aerobic physical activity per week, 55-70% peak heart rate (monitored via Fitbit), 4-6 on Borg's modified Rating of Perceived Exertion (RPE) scale, involving large muscle groups, over 3 to 5 days per week.
(2) Moderate-to-high intensity resistance exercises, 10-15 repetitions of each exercise, 4-6 on Borg's RPE scale, targeting large muscle groups, over 2 to 3 days per week.

Aerobic
All aerobic sessions will include a 3-minute light intensity warm-up and 2-minute cool down, equivalent to an RPE of 1-3 out of 10.. Aerobic exercises will be done via a treadmill, cycle ergometer, or land based walking as appropriate. Exercise intensity will be individualised from each participant’s percentage of their HRpeak or peak power output as measured during baseline testing. Aerobic exercise intensity will be monitored using the RPE scale and heart rate monitors, i.e., Fitbit.

Resistance
All strength sessions will be completed with a 5-minute cool down including static stretches and breathing. The resistance program will include 6 to 8 compound exercises focusing on major muscle groups to improve muscle strength and muscle mass such as squats, lunges, modified push-ups, etc. The dosage will include 1 to 3 sets of 8 to 15 repetitions performed at 55-70% of their 1 repetition maximum at baseline, with 1-2-minute rest between sets. The intensity and volume will progressively increase over the course of the 12-week program as tolerated. Technique will be closely monitored, and participants will be encouraged to perform the exercises with control.

Participants will attend 2-3 1-hour appointments per week with their AEP. The supervised sessions will be delivered either in an individual setting or in a group of up to three, as needed. Following the supervised period, participants will be given an individualised home based programme and will be monitored via the Fitbit and regular phone follow-up. An option to attend one=to-one 1-hour virtual supervised sessions will be offered. These will be done via an agreed upon video conferencing software, e.g., Zoom or Microsoft Teams. If participants are not meeting exercising as per their programme, they will be contacted using the escalating methods of email, text message or phone calls and will be invited to attend in-person supervised sessions.
Intervention code [1] 328599 0
Lifestyle
Intervention code [2] 328600 0
Behaviour
Intervention code [3] 329312 0
Treatment: Other
Comparator / control treatment
Participants will undergo bariatric surgery and receive usual clinical care which includes continued communication and reviews from their health team. Control participants will also be given a Fitbit device and have once a month phone follow-up with the AEP. The discussion will be based on current literature on exercise for bariatric surgery patients and will not be personalised.
Control group
Active

Outcomes
Primary outcome [1] 338251 0
Markers of neuroinflammation between intervention and control at 12 months after randomisation.
Timepoint [1] 338251 0
Baseline and 12 months after surgery.
Primary outcome [2] 338253 0
Markers of neuroinflammation with respect to baseline within groups.
Timepoint [2] 338253 0
Baseline and 12 months after surgery.
Secondary outcome [1] 435154 0
Brain volumes between groups and within groups at 12 months after randomisation with respect to baseline.
Timepoint [1] 435154 0
Baseline and 12 months after surgery.
Secondary outcome [2] 435155 0
Cognitive function.
Timepoint [2] 435155 0
Baseline, 6 and 12 months after surgery.
Secondary outcome [3] 435156 0
Flow-mediated dilatation (FMD; %).
Timepoint [3] 435156 0
Baseline, 4.5, 6, and 12 months after surgery.
Secondary outcome [4] 435157 0
Carotid intima-media thickness (cIMT; mm).
Timepoint [4] 435157 0
Baseline, 6 and 12 months after surgery.
Secondary outcome [5] 435158 0
Pulse wave velocity (PWV; m/s) and Augmentation Index (AI).
Timepoint [5] 435158 0
Baseline, 6 weeks, 3, 4.5, 6, and 12 months after surgery.
Secondary outcome [6] 435159 0
Peripheral and Central Blood Pressures (mmHg).
Timepoint [6] 435159 0
Baseline, 6 weeks, 4.5, 6, and 12 months after surgery.
Secondary outcome [7] 435160 0
Heart rate variability (HRV; ms2): Low Frequency (LF) and High Frequency (HF). This will be assessed as a composite outcome.
Timepoint [7] 435160 0
Baseline, 6 weeks, 3, 4.5, 6, and 12 months after surgery.
Secondary outcome [8] 435257 0
Whole body fat-free mass (%).
Timepoint [8] 435257 0
Baseline and 12 months after surgery.
Secondary outcome [9] 435261 0
Aerobic capacity.
Timepoint [9] 435261 0
Baseline, 6 weeks, 3, 4.5, 6, and 12 months after surgery.
Secondary outcome [10] 435284 0
Anthropometric measures including height (cm), body mass (kg), body mass index (BMI; kg/m2). This will be assessed as a composite outcome.
Timepoint [10] 435284 0
Baseline, 6 weeks, 3, 4.5, 6, and 12 months after surgery.
Secondary outcome [11] 435285 0
Composite metabolic control.
Timepoint [11] 435285 0
Baseline.
Secondary outcome [12] 435286 0
Glucose metabolism.
Timepoint [12] 435286 0
Baseline and 12 months after surgery.
Secondary outcome [13] 435287 0
Total sleep time (mins), sleep efficiency (%), and sleep-behaviours. This will be assessed as a composite outcome.
Timepoint [13] 435287 0
Baseline and 12 months after surgery.
Secondary outcome [14] 438167 0
Gut microbiome.
Timepoint [14] 438167 0
Baseline, 6 weeks, 3, 4.5, 6, and 12 months after surgery.
Secondary outcome [15] 438168 0
Psychosocial assessment.
Timepoint [15] 438168 0
Baseline and 12 months after surgery.
Secondary outcome [16] 438169 0
Diet quantity and quality. This will be assessed as a composite outcome.
Timepoint [16] 438169 0
Baseline and 12 months after surgery.
Secondary outcome [17] 438170 0
Metabolic biomarkers e.g., LDL Cholesterol.
Timepoint [17] 438170 0
Baseline, 6 weeks, 3, 4.5, 6, and 12 months after surgery.
Secondary outcome [18] 438172 0
Peripheral blood cell profiling e.g., WBC.
Timepoint [18] 438172 0
Baseline, 6 weeks, 3, 4.5, 6, and 12 months after surgery.
Secondary outcome [19] 438748 0
Bone mineral density (g/cm2) of the hip.
Timepoint [19] 438748 0
Baseline and 12-months after surgery.
Secondary outcome [20] 438749 0
Immune biomarkers e.g., IL-6.
Timepoint [20] 438749 0
Baseline, 6 weeks, 3, 4.5, 6, and 12 months after surgery.
Secondary outcome [21] 441069 0
Liver fat density (%).
Timepoint [21] 441069 0
Secondary outcome [22] 441070 0
Liver fat density (%).
Timepoint [22] 441070 0
Baseline and 12 months after surgery.
Secondary outcome [23] 441071 0
Adipose-derived extracellular vesicles.
Timepoint [23] 441071 0
Baseline and 12 months after surgery.
Secondary outcome [24] 441072 0
Adipose-derived extracellular vesicles.
Timepoint [24] 441072 0
At surgery.

Eligibility
Key inclusion criteria
- 18-80 years of age.
- Eligible for bariatric surgery.
- Willingness to provide informed consent and willingness to participate and comply with the study requirements
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Unable to undertake MRI due to size restrictions i.e., shoulder width more than 70 cm.
- History or clinical manifestation of any other significant metabolic, hematologic, pulmonary, cardio- vascular, gastrointestinal, neurologic, immune, hepatic, renal, urologic, muscular, and joint disorders, or cancer that, in the opinion of the investigator, would make the candidate ineligible for the study. For example, significant joint pain could interfere with adherence to the exercise program.
- Have objectively assessed cognitive impairment as assessed by the Montreal Cognitive Assessment (MoCA) i.e., total score less than 26.
- Non-MRI-compatible implanted devices or implants.
- Inability to exercise via supine ergometer.
- Claustrophobia.
- Psychiatric or behavioural problems (history of drug and alcohol abuse, eating disorder).
- Breastfeeding or pregnant women, or those intending to become pregnant before the scheduled end of the intervention.
- Unwilling to be assigned at random to the exercise or control intervention.
- Unwilling or unable to adhere to the rigors of the exercise intervention or evaluation schedule over the entire one-year period.
- Concurrent participation in any other interventional study.

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)
Participants will be randomised using computer generated random numbers, via a web-based randomisation system, i.e., central randomisation by computer. The statistician will design the randomisation schedule.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Web based randomisation system, validated by a statistician.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/01/2025
Actual
Date of last participant enrolment
Anticipated
31/12/2026
Actual
Date of last data collection
Anticipated
31/12/2027
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 26544 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 26545 0
Concord Repatriation Hospital - Concord
Recruitment hospital [3] 26546 0
Concord Private Hospital - Concord
Recruitment hospital [4] 26547 0
The Northern Beaches Hospital - Frenchs Forest
Recruitment postcode(s) [1] 42584 0
2050 - Camperdown
Recruitment postcode(s) [2] 42585 0
2139 - Concord
Recruitment postcode(s) [3] 42586 0
2086 - Frenchs Forest

Funding & Sponsors
Funding source category [1] 316057 0
Government body
Name [1] 316057 0
National Health and Medical Research Council
Country [1] 316057 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
Country
Australia
Secondary sponsor category [1] 318221 0
None
Name [1] 318221 0
Address [1] 318221 0
Country [1] 318221 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314877 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 314877 0
https://www.slhd.nsw.gov.au/rpa/research/
Ethics committee country [1] 314877 0
Australia
Date submitted for ethics approval [1] 314877 0
26/02/2024
Approval date [1] 314877 0
08/05/2024
Ethics approval number [1] 314877 0

Summary
Brief summary
This randomised controlled trial aims to evaluate the effects of marked weight loss, via bariatric surgery, combined with a personalised exercise intervention on markers of brain inflammation. This study will allow us to explore the link between excessive adiposity-induced systemic chronic inflammation, metabolic abnormalities, and neuroinflammation. We hypothesise that bariatric surgery, i.e., marked weight loss, and exercise will result in attenuated neuroinflammation (as measured by neuroimaging), improvements in cognitive function, improvements in immune-inflammatory markers, and improvements in cardiometabolic biomarkers at 12 months compared to control.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 133026 0
A/Prof Laura Piccio
Address 133026 0
Level 5 West D17 – Education and Research Hub The Charles Perkins Centre Camperdown The University of Sydney NSW 2006
Country 133026 0
Australia
Phone 133026 0
+61 2 8627 7413
Fax 133026 0
Email 133026 0
[email protected]
Contact person for public queries
Name 133027 0
Reeja Nasir
Address 133027 0
Level 2 West D17 – Education and Research Hub The Charles Perkins Centre Camperdown The University of Sydney NSW 2006
Country 133027 0
Australia
Phone 133027 0
+61 2 8627 7413
Fax 133027 0
Email 133027 0
[email protected]
Contact person for scientific queries
Name 133028 0
Laura Piccio
Address 133028 0
Level 5 West D17 – Education and Research Hub The Charles Perkins Centre Camperdown The University of Sydney NSW 2006
Country 133028 0
Australia
Phone 133028 0
+61 2 8627 7413
Fax 133028 0
Email 133028 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Non-identifiable participant data will be shared based upon the research proposal and subsequent discretion of the Principal Investigator. This will include all data.
When will data be available (start and end dates)?
Data will be available after completion of the study (2027) and there will be no end date.
Available to whom?
Researchers can contact the Principal Investigator if they have a research question. The Principal Investigator will decide to release data based upon the proposal.
Available for what types of analyses?
This will depend on the research proposal and discretion of the Principal Investigator.
How or where can data be obtained?
Contact the Principal Investigator by email ([email protected]).


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.