Obesity and Overweight
Conditions
Keywords
Obesity, Bariatric Surgery, Exercise, Neuroinflammation, Cognitive Function
Brief summary
This study will test how significant weight loss through bariatric surgery, combined with a personalised exercise program, affects brain inflammation. Th investigators want to understand the connection between obesity-related body inflammation, metabolic issues, and brain inflammation and function.
Detailed description
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 the investigators to explore the link between excessive adiposity-induced systemic chronic inflammation, metabolic abnormalities, and neuroinflammation. The investigators 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. This study is a parallel group, randomised controlled trial. A 1:1 allocation ratio will be applied to either the intervention group (bariatric surgery and usual care with exercise) or control group (bariatric surgery and usual care). Participants in both arms will be followed over a period of 12 months after surgery. A comprehensive set of evaluations will be performed prior to the surgery, with follow-up in-person evaluations at 6 weeks and 3, 4.5, 6, and 12 months. The primary objective is to evaluate the effect of bariatric surgery and exercise on neuroinflammation compared to control at 12-months. This will be assessed via a novel neuroimaging technique. Secondary and exploratory objectives are to evaluate the effect of bariatric surgery and exercise on brain structure, cognition, immune-inflammatory markers, cardiometabolic markers, psychosocial factors, diet, and physical functioning compared to control. The investigators would also like to explore within-group differences for all the above from baseline to 12-months.
Interventions
BEHAVIORALExercise
Exercise.
Sponsors
Washington University School of Medicine
Sydney Local Health District
Northern Sydney Local Health District
University of Sydney
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Markers of neuroinflammation | Baseline and 12 months after surgery. | Between intervention and control at 12 months after surgery. Assessed via DBSI-MRI. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cognitive function | Baseline, 6 and 12 months after surgery. | This will be a composite outcome. Validated questionnaires such as Stroop Test. |
| Anthropometric measures including height (cm), body mass (kg), body mass index (BMI; kg/m2) | Baseline, 6 weeks, 3, 4.5, 6, and 12 months after surgery. | This will be assessed as a composite outcome. Assessed via a wall-mounted stadiometer and digital scales. |
| Metabolic biomarkers (e.g., LDL Cholesterol), peripheral blood cell profiling (e.g., WBC), and immune biomarkers (e.g., IL-6) | Baseline, 6 weeks, 3, 4.5, 6, and 12 months after surgery. | Venous blood collection, analysed via ELISA. |
| Brain volumes | Baseline and 12 months after surgery. | Between groups and within groups at 12 months after randomisation with respect to baseline. Assessed via T1 and T2 MRI. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Heart rate variability (HRV; ms2) | Baseline, 6 weeks, 3, 4.5, 6, and 12 months after surgery. | This will be assessed as a composite outcome. Assessed via the Human Non-Invasive Blood Pressure System. |
| Bone mineral density (g/cm2) of the hip | Baseline and 12 months after surgery. | Assessed via the Hologic Discovery W Dual Energy X-Ray (DEXA) Absorptiometry Scanner. |
| Whole body fat-free mass (%) | Baseline and 12 months after surgery. | Assessed via the Hologic Discovery W Dual Energy X-Ray (DEXA) Absorptiometry Scanner. |
| Total sleep time (mins) | Baseline and 12 months after surgery. | Assessed via the Nox-T3+ Device. |
| Sleep efficiency (%) | Baseline and 12 months after surgery. | Assessed via the Nox-T3+ Device. |
| Flow-mediated dilatation (FMD; %) | Baseline, 4.5, 6, and 12 months after surgery. | Assessed via high-resolution ultrasound and semi-automated edge detection software. |
| Composite metabolic control | Baseline. | Glucose and insulin response to oral glucose tolerance test (75g) at 0, 30, 60, 120 minutes. |
| Diet quantity and quality | Baseline, 6 and12 months after surgery. | This will be assessed as a composite outcome. This will be assessed via a 3-day Food Diary, analysed with FoodWorks. |
| Changes in health-related quality of life | Baseline and 12 months after surgery. | The Medical Outcomes Study Short-Form 36 Health Status Survey (SF-36). The scores will be standardised according to the normative values for the Australian context. |
| Changes in social-related quality of life | Baseline and 12 months after surgery. | The Australian version of the Assessment of Quality of Life (AQoL). |
| Sleep-behaviours | Baseline and 12 months after surgery. | Assessed via validated questionnaires (STOP BANG, SAGIC, and Epworth Sleepiness Scale). |
| Carotid intima-media thickness (cIMT; mm) | Baseline and 12 months after surgery. | Assessed via high-resolution ultrasound and semi-automated edge detection software. |
| Pulse wave velocity (PWV; m/s) | Baseline, 6 weeks, 3, 4.5, 6, and 12 months after surgery. | Assessed via the SphygmoCor XCEL System. |
| Augmentation Index (AI) | Baseline, 6 weeks, 3, 4.5, 6, and 12 months after surgery. | Assessed via the SphygmoCor XCEL System. |
| Peripheral and Central blood pressures (mmHg) | Baseline, 6 weeks, 3, 4.5, 6, and 12 months after surgery. | Assessed via the SphygmoCor XCEL System. |
Countries
Australia
Contacts
Primary ContactStudy Coordinator
Backup ContactCoordinating Principal Investigator
Outcome results
None listed