Clinical trial NCT06309238: Intensive Weight Loss Intervention Versus Bariatric Surgery for Adults With Severe and Complex Obesity: the LightBAR Randomised Trial
Official title: Intensive Weight Loss Intervention Versus Bariatric Surgery for Adults With Severe and Complex Obesity: the LightBAR Randomised Trial. Lighthouse Consortium on Obesity Management (LightCOM) Trial no 4
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Obesity
Lead sponsor: Copenhagen University Hospital, Hvidovre
Sponsor class: OTHER
Collaborators: name: University of Copenhagen
name: University of Southern Denmark
name: University of Oxford
name: Copenhagen Trial Unit, Center for Clinical Intervention Research
First posted: 2024-03-13
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: With this trial, the aim is to assess the benefits and harms of a non-surgical intensive weight loss intervention that includes total dietary replacements, behavioural support and weight-loss medication compared with bariatric surgery for people with severe and complex obesity. The interpretation of the results will help inform future care pathways for people with obesity in whom bariatric surgery is currently the only available effective treatment option.

Detailed description: In the LightBAR trial, an intensive weight loss (IWL) intervention will be compared with bariatric surgery. The IWL consists of three phases:

'Induction' phase (week 0-12 after randomisation): total dietary replacement (TDR) programme and behavioural support with weight loss medication (WLM) if rate of weight loss is insufficient.

'Weight loss continuation' phase (week 13-32 after randomisation): progression of dietary programme including reduction in use of TDR products, reintroduction of healthy foods, with behavioural support, introduction of physical activity, WLM (as required).

'Maintenance' phase (week 33-104 after randomisation): Continued healthy diet and physical activity with WLM (if required), with return to induction phase if weight regain occurs induction, weight loss continuation, maintenance. The IWL lasts two years, and includes total dietary replacements, behavioural support, and weight loss medication. Bariatric surgery will be standard Roux-en-Y gastric bypass or sleeve gastrectomy.

Eligibility criteria: Please note that participants need to be invited in order to take part in the trial.

Inclusion Criteria:

* Aged 18 to 60 years (inclusive) at time of screening.
* Eligible for and willing to undergo bariatric surgery, i.e., fulfilment of criteria for bariatric surgery from the respective national health authorities:

  * DK: BMI ≥ 35 kg/m2 with one or more of the following: T2D, severe hypertension, sleep apnoea requiring treatment, symptomatic arthrosis in lower extremities, female infertility related to overweight, or BMI\>40 kg/m2 with other strong medical reasons for weight loss (28). Prior to surgery, an 8% weight loss is required as well as smoking cessation.
  * UK: BMI of 35 kg/m2 to 40 kg/m2 and other significant disease (e.g., type 2 diabetes or high blood pressure), or BMI ≥40 kg/m2. Has been or is willing to receive intensive management in a specialist tier 3 obesity service (29).
* Fit for anaesthesia and surgery.
* Informed consent.

Exclusion Criteria:

* Prior bariatric or hiatal surgery, not including intragastric balloons or duodenal-jejunal bypass sleeve (Endobarrier™ or similar) if the device has been removed \>1 year before screening.
* Use of any WLM (including liraglutide and semaglutide for diabetes) within last 3 months.
* Conditions that contraindicate or complicate total diet replacement (including type 1 diabetes or other diabetes requiring basal bolus insulin therapy or insulin pump therapy (for Denmark) and any diabetes requiring insulin therapy (for UK), phenylketonuria, or other conditions requiring strict adherence to special diets).
* Conditions that contraindicate or complicate treatment with GLP-1 receptor analogues (including history of pancreatitis or known allergies).
* Conditions that contraindicate or complicate bariatric surgery (GI motility disorders, large abdominal wall hernia, large hiatus hernia (\>5cm), Crohn's disease, liver cirrhosis, or other conditions preventing laparoscopic bariatric surgery e.g. multiple previous abdominal surgery).
* Conditions that contraindicate or complicate study adherence and bariatric surgery (mental disorder, unstable psychiatric disease, recent history of alcohol/medication abuse, cancer treatment within 5 years).
* Pregnant or planning pregnancy in the next two years or currently breast feeding.
* Not achieving a 5% weight loss within 12 weeks prior to randomisation.
* People taking part in other research involving multidisciplinary obesity treatment that would compromise their participation in this trial.
* Another member of the household enrolled in the trial.
* Diagnosis of or treatment for severe eating disorder within the last 6 months.

Primary outcomes:
measure: MetS-Z
timeFrame: 104 weeks after randomisation
Secondary outcomes:
measure: Weight
timeFrame: 104 weeks after randomisation
measure: Gait speed
timeFrame: 104 weeks after randomisation
measure: Short-Form-36, mental component score
timeFrame: 104 weeks after randomisation
Other outcomes:
measure: SAE
timeFrame: 104 weeks after randomisation
measure: Proportion of participants with at least one adverse events (AE) of special interest. Each of the AE will also be assessed individually exploratorily.
timeFrame: 104 weeks after randomisation
measure: Cardiometabolic health - metabolic syndrome
timeFrame: 104 weeks after randomisation
measure: Cardiometabolic health - blood pressure
timeFrame: 104 weeks after randomisation
measure: Cardiometabolic health - pulse
timeFrame: 104 weeks after randomisation
measure: Cardiometabolic health - glucose
timeFrame: 104 weeks after randomisation
measure: Cardiometabolic health - Hb1Ac
timeFrame: 104 weeks after randomisation
measure: Cardiometabolic health - insulin
timeFrame: 104 weeks after randomisation
measure: Cardiometabolic health - HOMA2-IR
timeFrame: 104 weeks after randomisation
measure: Cardiometabolic health - lipids
timeFrame: 104 weeks after randomisation
measure: Cardiometabolic health - eGFR
timeFrame: 104 weeks after randomisation
measure: Cardiometabolic health - hsCRP
timeFrame: 104 weeks after randomisation
measure: Cardiometabolic health - Fib-4
timeFrame: 104 weeks after randomisation
measure: Cardiometabolic health - proteinuria
timeFrame: 104 weeks after randomisation
measure: Cardiometabolic health - TSH
timeFrame: 104 weeks after randomisation
measure: Weight and body composition - weight loss
timeFrame: 104 weeks after randomisation
measure: Weight and body composition - waist circumference
timeFrame: 104 weeks after randomisation
measure: Weight and body composition - body fat and lean body mass
timeFrame: 104 weeks after randomisation
measure: Physical functioning - sedentary and active
timeFrame: 104 weeks after randomisation
measure: Physical functioning - sit to stand test
timeFrame: 104 weeks after randomisation
measure: Medication use
timeFrame: 104 weeks after randomisation
measure: Micronutrient status, assessed as proportion of participants with deficiency
timeFrame: During follow-up until 104 weeks after randomisation
measure: Bone mineral density (BMD) assessed by DXA
timeFrame: 104 weeks after randomisation
measure: Sleep - ESS
timeFrame: 104 weeks after randomisation
measure: Sleep - sleep and wake time
timeFrame: 104 weeks after randomisation
measure: Sleep - sleep movement
timeFrame: 104 weeks after randomisation
measure: Health-related quality of life and mental health - EQ-5D-5L, index score
timeFrame: 104 weeks after randomisation
measure: Health-related quality of life and mental health - EQ-5D-5L, VAS
timeFrame: 104 weeks after randomisation
measure: Health-related quality of life and mental health - SF-36
timeFrame: 104 weeks after randomisation
measure: Health-related quality of life and mental health - EDE-Q
timeFrame: 104 weeks after randomisation
measure: Health-related quality of life and mental health - WBIS-M
timeFrame: 104 weeks after randomisation
measure: Health-related quality of life and mental health - MDI
timeFrame: 104 weeks after randomisation
measure: Labour market attachment - WPAI
timeFrame: 104 weeks after randomisation
measure: Labour market attachment - days of sick leave
timeFrame: 104 weeks after randomisation
measure: Continuous glucose monitoring - hypoglycaemic range
timeFrame: 104 weeks after randomisation:
measure: Continuous glucose monitoring - hypoglycaemic events
timeFrame: 104 weeks after randomisation:
measure: Continuous glucose monitoring - glucose variability
timeFrame: 104 weeks after randomisation:
measure: Continuous glucose monitoring - hypoglycaemic symptoms
timeFrame: 104 weeks after randomisation:
measure: Pending additional funding: Genetic profiles' (using comprehensive genetic mapping) association with the metabolic and/or weight loss response to IWL vs bariatric surgery
timeFrame: 104 weeks after randomisation
measure: Health economy: Within-trial cost-effectiveness analysis - quality of life
timeFrame: 104 weeks after randomisation
measure: Health economy: Within-trial cost-effectiveness analysis - costs
timeFrame: 104 weeks after randomisation
measure: Health economy: Within-trial cost-effectiveness analysis - QALY
timeFrame: 104 weeks after randomisation
measure: Health economy: Model-based cost-effectiveness analysis - QALY
timeFrame: 104 weeks after randomisation
measure: Health economy: Model-based cost-effectiveness analysis - healthcare costs
timeFrame: 104 weeks after randomisation
measure: Health economy: Model-based cost-effectiveness analysis - cost effectiveness ratios
timeFrame: 104 weeks after randomisation
measure: Long-term effects - mortality and major cardiovascular disease (CVD)
timeFrame: 5, 10 and 20 years after randomisation
measure: Long-term effects - prescription patterns
timeFrame: 5, 10 and 20 years after randomisation
measure: Long-term effect - incident cancer
timeFrame: 5, 10 and 20 years after randomisation
measure: Long-term effect - surgical procedures
timeFrame: 5, 10 and 20 years after randomisation
measure: Long-term effect - fracture risk
timeFrame: 5, 10 and 20 years after randomisation
measure: Long-term effect - health economic and labour market attachment, employment status
timeFrame: 5, 10 and 20 years after randomisation
measure: Long-term effect - health economic and labour market attachment, salary
timeFrame: 5, 10 and 20 years after randomisation
measure: Long-term effect - health economic and labour market attachment, absence
timeFrame: 5, 10 and 20 years after randomisation
measure: Long-term effect - health economic and labour market attachment, sick leave
timeFrame: 5, 10 and 20 years after randomisation
measure: Long-term effect - health economic and labour market attachment, long-term sick leave
timeFrame: 5, 10 and 20 years after randomisation
Locations:
city: Aarhus
country: Denmark
facility: Steno Diabetes Center Aarhus, Aarhus Universitets Hospital
city: Esbjerg
country: Denmark
facility: The Department of Medicine and Department of Surgery, University Hospital of South West Jutland
city: Hvidovre
country: Denmark
facility: The Department of Medicine and the Gastro Unit, Copenhagen University Hospital - Amager and Hvidovre
city: Viborg
country: Denmark
facility: Department of Surgery, Viborg Regional Hospital
city: Truro
country: United Kingdom
facility: The Royal Cornwall Hospital
state: Cornwall
city: Cosham
country: United Kingdom
facility: Queen Alexandra Hospital
state: Portsmouth
city: Chichester
country: United Kingdom
facility: St Richard's Hospital
state: Sussex
city: Bristol
country: United Kingdom
facility: Southmead Hospital, North Bristol NHS Trust
city: Taunton
country: United Kingdom
facility: Musgrove Park Hospital, Somerset Foundation NHS Trust
Study officials:
affiliation: Department of Medicine, Copenhagen University Hospital - Amager and Hvidovre
name: Carsten Dirksen, Ass Professor
role: STUDY_CHAIR
References: