Intensive Weight Loss Intervention Versus Bariatric Surgery for Adults With Severe and Complex Obesity: the LightBAR Randomised Trial

Obesity Clinical Trial

— LightBAR  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06309238
• Other study ID #: LightBAR
• Status: Recruiting
• Phase: N/A
• Start date: May 2024
• Est. completion date: December 2048

Study information

• Verified date: May 2024
• Source: Copenhagen University Hospital, Hvidovre
• Contact: Kirstine N Bojsen-Møller, MD, PhD
• Phone: +45 3862 3862
• Email: kirstine.nyvold.bojsen-moeller[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: December 2048
• Est. primary completion date: December 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Obesity
• Weight Loss

Intervention

Behavioral:
• Intensive weight loss intervention
Intensive weight loss intervention, incl. total meal replacements, behavioural support, and weight loss medication

Procedure:
• Bariatric surgery
Roux-en-Y Gastric Bypass (RYGB) or Sleeve Gastrectomy (SG)

Locations

Country	Name	City	State
Denmark	Steno Diabetes Center Aarhus, Aarhus Universitets Hospital	Aarhus
Denmark	The Department of Medicine and Department of Surgery, University Hospital of South West Jutland	Esbjerg
Denmark	The Department of Medicine and the Gastro Unit, Copenhagen University Hospital - Amager and Hvidovre	Hvidovre
Denmark	The Department of Medicine and the Department of Surgery, Zealand University Hospital Køge	Køge
Denmark	Department of Surgery, Viborg Regional Hospital	Viborg
United Kingdom	Southmead Hospital, North Bristol NHS Trust	Bristol
United Kingdom	Southampton General Hospital, University Hospital Southampton NHS Foundation Trust	Southampton
United Kingdom	Musgrove Park Hospital, Somerset Foundation NHS Trust	Taunton

Sponsors (6)

Lead Sponsor	Collaborator
Carsten Dirksen	Copenhagen Trial Unit, Center for Clinical Intervention Research, University of Bristol, University of Copenhagen, University of Oxford, University of Southern Denmark

Countries where clinical trial is conducted

Denmark,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	SAE	Proportion of participants with at least one serious adverse event (according to ICH-GCP guidelines)	104 weeks after randomisation
Other	Proportion of participants with at least one adverse events (AE) of special interest. Each of the AE will also be assessed individually exploratorily.	Anaemia (haemoglobin <6.8 mmol/L (<110 g/L)); Severe and persistent/recurrent gastrointestinal symptoms (i.e.: reflux, nausea/vomiting, constipation, diarrhoea, abdominal pain - defined according to a modification of Rome IV criteria).; Symptomatic hypotension (episode with loss of consciousness, seizures, or other severe mental impairments due to suspected orthostatic hypotension).; Hypoglycaemia (episode with loss of consciousness, seizures or other severe mental impairments requiring third party assistance (level 3) or documented glucose concentration <3.0 mmol/l (level 2) or initiation of medication related to documented reactive hypoglycaemia).; Incident alcohol abuse, other addictive disorder, self-inflicted harm, or eating disorders (Initiation of treatment (behavioural or pharmacological) for addictive disorders or documented self-inflicted harm not requiring hospitalisation (outpatient visits to emergency rooms, GP etc).	104 weeks after randomisation
Other	Cardiometabolic health - metabolic syndrome	Proportion of participants with metabolic syndrome	104 weeks after randomisation
Other	Cardiometabolic health - blood pressure	Systolic and diastolic blood pressure (mmHg)	104 weeks after randomisation
Other	Cardiometabolic health - pulse	Pulse rate (beats per minute)	104 weeks after randomisation
Other	Cardiometabolic health - glucose	Fasting glucose concentration (mmol/l)	104 weeks after randomisation
Other	Cardiometabolic health - Hb1Ac	Haemoglobin A1c (mmol/mol)	104 weeks after randomisation
Other	Cardiometabolic health - insulin	Fasting insulin concentration (pmol/L)	104 weeks after randomisation
Other	Cardiometabolic health - HOMA2-IR	HOMA2-IR (calculated from glucose and C-peptide concentration) (ratio)	104 weeks after randomisation
Other	Cardiometabolic health - lipids	Fasting lipid profile (HDL, LDL and triglycerides) (mmol/L)	104 weeks after randomisation
Other	Cardiometabolic health - eGFR	Estimated Glomerular Filtration Rate (eGFR), creatinine (µmol/L), calculated from creatinine, sex and years	104 weeks after randomisation
Other	Cardiometabolic health - hsCRP	High-sensitivity C-reactive protein (hsCRP), mg/L	104 weeks after randomisation
Other	Cardiometabolic health - Fib-4	Fib-4 (ALT/AST/platelets) (ratio)	104 weeks after randomisation
Other	Cardiometabolic health - proteinuria	Proteinuria, measured as urine albumin/creatinine (ratio)	104 weeks after randomisation
Other	Cardiometabolic health - TSH	Thyroid-stimulating hormone (IU/L)	104 weeks after randomisation
Other	Weight and body composition - weight loss	Proportion of participants with body weight loss of =20% and =15%	104 weeks after randomisation
Other	Weight and body composition - waist circumference	Waist circumference (cm)	104 weeks after randomisation
Other	Weight and body composition - body fat and lean body mass	Body fat (%) and lean body mass (%) assessed by DXA	104 weeks after randomisation
Other	Physical functioning - sedentary and active	Time spent sedentary and active (moderate to vigorous physical activity) estimated by SENS activity tracker (minutes/day)	104 weeks after randomisation
Other	Physical functioning - sit to stand test	Number of sit to stands completed 30 Second Sit to Stand test	104 weeks after randomisation
Other	Medication use	Glucose-lowering medications (number, type); Lipid-lowering medications (number, type); Blood pressure-lowering medications (number, type); Medication for pain relief (number, type); Weight loss medication (number, type); Medication used for psychiatric disorders (antidepressants, anxiolytics, antipsychotics) (number, type)	104 weeks after randomisation
Other	Micronutrient status, assessed as proportion of participants with deficiency	Iron; B12; Folate; Vitamin D; Hyperparathyroidism	During follow-up until 104 weeks after randomisation
Other	Bone mineral density (BMD) assessed by DXA	BMD of weight bearing regions: hip (total hip and femoral neck) and lumbar region; BMD of non-weight bearing region: forearm of non-dominant hand (ultradistal and 1/3 distal radius)	104 weeks after randomisation
Other	Sleep - ESS	Epworth Sleepiness Scale Questionnaire Score (scale from 0-24, higher scores indicate more sleepiness)	104 weeks after randomisation
Other	Sleep - sleep and wake time	Estimated sleep and wake time (minutes/day)	104 weeks after randomisation
Other	Sleep - sleep movement	Movement during sleep estimated by SENS.	104 weeks after randomisation
Other	Health-related quality of life and mental health - EQ-5D-5L, index score	EQ-5D-5L, index score (score between -1 and 1, higher scores indicate better health)	104 weeks after randomisation
Other	Health-related quality of life and mental health - EQ-5D-5L, VAS	EQ-5D-5L, VAS score (scale from 0-100, higher scores indicate better health)	104 weeks after randomisation
Other	Health-related quality of life and mental health - SF-36	Short-Form-36, physical component score (scale from 0-100, higher scores indicate better physical health)	104 weeks after randomisation
Other	Health-related quality of life and mental health - EDE-Q	Eating Disorder Examination Questionnaire (EDE-Q) score (scale from 0 to 6, higher scores indicate higher degree of eating disorder)	104 weeks after randomisation
Other	Health-related quality of life and mental health - WBIS-M	Weight Bias Internalization Scale (WBIS-M) score (scale from 1-7, higher scores indicate higher degree of internalised weight bias)	104 weeks after randomisation
Other	Health-related quality of life and mental health - MDI	Major Depression Inventory (MDI) (scale from 0-50, higher scores indicate more symptoms of depression)	104 weeks after randomisation
Other	Labour market attachment - WPAI	Work productivity and impairment (WPAI) score points (scale from 0-100, higher scores indicate more limitations in ability to work and lower productivity)	104 weeks after randomisation
Other	Labour market attachment - days of sick leave	Self-reported number of days sick leave during follow-up	104 weeks after randomisation
Other	Continuous glucose monitoring - hypoglycaemic range	Time spent in level 1 hypoglycaemic range (interstitial fluid glucose (IFG) <3.9 mmol/L)	104 weeks after randomisation:
Other	Continuous glucose monitoring - hypoglycaemic events	Number of hypoglycaemic events (15 minutes of IFG<3 mmol/L)	104 weeks after randomisation:
Other	Continuous glucose monitoring - glucose variability	Glucose variability (CV)	104 weeks after randomisation:
Other	Continuous glucose monitoring - hypoglycaemic symptoms	Self-reported hypoglycaemic symptoms as recorded in hypoglycaemic symptom diary (reported descriptively)	104 weeks after randomisation:
Other	Pending additional funding: Genetic profiles' (using comprehensive genetic mapping) association with the metabolic and/or weight loss response to IWL vs bariatric surgery	Common gene variants with low to moderate effect on the phenotype for the construction of aggregate genetic risk scores; Rare variants with potential functional effects in genes known to harbour high-impact obesity variants e.g. MC4R, LEP, LEPR, POMC, PCSK1, SIM1, NTRK2, MC3R, MRAP2, BDNF, SH2B1, KSR2	104 weeks after randomisation
Other	Health economy: Within-trial cost-effectiveness analysis - quality of life	Quality of life (measured using EQ-5D-5L)	104 weeks after randomisation
Other	Health economy: Within-trial cost-effectiveness analysis - costs	24-month costs, DKK	104 weeks after randomisation
Other	Health economy: Within-trial cost-effectiveness analysis - QALY	Incremental cost per quality-adjusted-life-year (QALY) gained, DKK	104 weeks after randomisation
Other	Health economy: Model-based cost-effectiveness analysis - QALY	Predicted lifetime QALYs gained	104 weeks after randomisation
Other	Health economy: Model-based cost-effectiveness analysis - healthcare costs	Predicted lifetime healthcare costs, DKK	104 weeks after randomisation
Other	Health economy: Model-based cost-effectiveness analysis - cost effectiveness ratios	Long-term incremental cost effectiveness ratios	104 weeks after randomisation
Other	Long-term effects - mortality and major cardiovascular disease (CVD)	Proportion of participants who die from any cause; Proportion of participants with a major CVD outcome consisting of any of the following (each of the components will be assessed exploratively): myocardial infarction, stroke, hospitalisation for angina, coronary-artery bypass grafting, percutaneous coronary intervention, hospitalisation for heart failure, peripheral vascular disease	5, 10 and 20 years after randomisation
Other	Long-term effects - prescription patterns	Proportion of participants on glucose-lowering medications; Proportion of participants on lipid-lowering medications; Proportion of participants on blood pressure-lowering medications; Proportion of participants on medication for pain relief; Proportion of participants on weight loss medication; Proportion of participants on medication used for psychiatric disorders (antidepressants, anxiolytics, antipsychotics)	5, 10 and 20 years after randomisation
Other	Long-term effect - incident cancer	Proportion of participants with any diagnosis of cancer; Proportion of participants with cancers known to be associated with obesity: GI tract including liver and kidney and reproduction organs (including breast for women and prostate for men)	5, 10 and 20 years after randomisation
Other	Long-term effect - surgical procedures	Proportion of participants with any surgical procedure related to bariatric surgery: revisional surgery for late complications eg internal hernia, stomal ulcer; and conversion surgery eg change of operation from index procedure to another for weight regain or complications; or new bariatric procedures; Proportion of participants with surgical procedures related to obesity and/or weight loss: eg cholecystectomy, body contouring surgery, elective arthroplasty	5, 10 and 20 years after randomisation
Other	Long-term effect - fracture risk	Proportion of participants with any fracture; Proportion of participants with major osteoporotic fracture (hip, spine, wrist, humerus)	5, 10 and 20 years after randomisation
Other	Long-term effect - health economic and labour market attachment, employment status	Employment status each participant	5, 10 and 20 years after randomisation
Other	Long-term effect - health economic and labour market attachment, salary	Salary for each participant	5, 10 and 20 years after randomisation
Other	Long-term effect - health economic and labour market attachment, absence	Number of absence days	5, 10 and 20 years after randomisation
Other	Long-term effect - health economic and labour market attachment, sick leave	Proportion of participants with any sick leave	5, 10 and 20 years after randomisation
Other	Long-term effect - health economic and labour market attachment, long-term sick leave	Proportion of participants with long-term sick leave (more than 4 weeks continuous sickness absence)	5, 10 and 20 years after randomisation
Primary	MetS-Z	Metabolic syndrome severity Z-score	104 weeks after randomisation
Secondary	Weight	Weight (kg)	104 weeks after randomisation
Secondary	Gait speed	4-metre gait speed (m/s)	104 weeks after randomisation
Secondary	Short-Form-36, mental component score	Quality of life, SF36-mental component score (scale from 0-100, higher scores indicate better mental health)	104 weeks after randomisation

External Links

•   LightCOM website