Clinical trial NCT06321458: Intensive Weight Loss Intervention Versus Usual Care for Adults With Severe and Complex Obesity
Official title: Intensive Weight Loss Intervention Versus Usual Care for Adults With Severe and Complex Obesity: the LightWAY Randomised Trial: Lighthouse Consortium on Obesity Management (LightCOM) Trial no 3
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: 2024-03-20
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Due to the nature of the interventions, it will not be possible to blind the participants or the healthcare providers administering the interventions. In all other aspects of the trial, blinding will be employed. Outcome assessors will be blinded to group allocation. Participants will also be requested not to disclose their allocation when outcomes are assessed.

Statisticians and investigators drawing conclusions will be fully blinded. The statistical analyses will be conducted with the intervention groups coded as e.g., 'A' and 'B'. The Steering Committee will write two abstracts while the blinding is intact; one assuming the experimental intervention group is 'A' and the control intervention group is 'B', and one assuming the opposite. After these two abstracts have both obtained consensus, the code will be broken by the data manager.
Primary purpose: TREATMENT

Brief summary: In this trial, the aim is to assess the clinical benefits and harms, as well as cost-effectiveness of an intensive weight loss (IWL) intervention that includes total dietary replacements, behavioural support and weight-loss medication compared with existing weight management programmes within primary care for people with severe and complex obesity.

Detailed description: In the LightWAY trial, an intensive weight loss (IWL) intervention will be compared with with usual care. The IWL lasts two years, and includes total dietary replacements, behavioural support, and weight loss medication in 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.

Usual care will differ between the two countries (Denmark and the United Kingdom).

In Denmark, participants will receive a pamphlet on current obesity management guidelines from the Danish National Board of Health, and will be advised to contact their GP for potential referral to local municipality-based obesity management programmes. Furthermore, a notification will be sent to the participant's GP, informing that the participant has been enrolled in the trial and is randomised to usual care. The availability and structure of current obesity programmes varies between municipalities.

In the United Kingdom, participants are eligible for referral into an NHS Tier 3 weight management service. These services are commissioned by integrated care boards, and can therefore differ slightly across the 42 regions within the UK. These are specialist weight management clinics that provide non-surgical, intensive medical management with a multidisciplinary approach to care. These clinics often consist of specialist doctors, nurses, dieticians and physiotherapists/exercise therapists, and include psychological support.

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

Inclusion Criteria:

1. Age ≥18 years and ≤60 years old at screening.
2. Has severe and complex obesity i.e. BMI\>35 or \>32.5 in people with South Asian, Chinese, other Asian, Middle Eastern, Black African or African-Caribbean family backgrounds and with one or more of these specific adiposity-related chronic diseases of cardiovascular disease, type 2 diabetes, hypertension, non-alcoholic steatosis, or sleep apnoea.
3. Provides informed consent.

Exclusion Criteria:

1. Intending to become pregnant in the next two years or pregnant or breastfeeding.
2. Use of WLM or GLP-1 agonist treatment within the last three months.
3. Currently being treated for cancer other than oestrogen antagonist therapy or non-melanoma skin cancer.
4. Prior bariatric surgery, not including laparoscopic gastric banding, intragastric balloons or duodenal-jejunal bypass sleeve (Endobarrier™ or similar) if the device has been removed \>1 year before screening.
5. Diagnosis of or treatment for severe eating disorder within the last 6 months.
6. Any other disease that markedly compromises the participant's ability to adhere to the treatment programme or follow-up or is likely to mean that weight loss will not improve the person's length or quality of life, such as conditions limiting life expectancy.
7. Conditions that contraindicate or complicate TDR (including type 1 diabetes or other diabetes requiring insulin therapy, phenylketonuria, or other conditions requiring special diets).
8. Conditions that contraindicate or complicate GLP-1 treatment (including history of pancreatitis)
9. Taking part in other research involving multidisciplinary obesity treatment would compromise participation in this trial.
10. Another member of the household enrolled in the trial.

Primary outcomes:
measure: MetS-Z
timeFrame: 104 weeks after randomisation
measure: Weight
timeFrame: 104 weeks after randomisation
Secondary outcomes:
measure: Short-Form-36, mental component score
timeFrame: 104 weeks after randomisation
measure: Gait speed
timeFrame: 104 weeks after randomisation
measure: Weight loss (20%)
timeFrame: 104 weeks after randomisation
Other outcomes:
measure: SAE
timeFrame: 104 weeks after randomisation
measure: Incident eating disorders
timeFrame: 104 weeks after randomisation
measure: Bone mineral density (BMD) assessed by DXA
timeFrame: 104 weeks after randomisation
measure: Body composition - waist circumference
timeFrame: 104 weeks after randomisation
measure: Body composition - fat percentage
timeFrame: 104 weeks after randomisation
measure: Body composition - weight loss (10%)
timeFrame: 104 weeks after randomisation
measure: Physical functioning - SENS
timeFrame: 104 weeks after randomisation
measure: Physical functioning - SF-36
timeFrame: 104 weeks after randomisation
measure: Physical functioning - sit to stand test
timeFrame: 104 weeks after randomisation
measure: Sleep
timeFrame: 104 weeks after randomisation
measure: Medications during the intervention period
timeFrame: 104 weeks after randomisation
measure: Metabolic health - blood pressure
timeFrame: 104 weeks after randomisation
measure: Metabolic health - pulse
timeFrame: 104 weeks after randomisation
measure: Metabolic health - Hb1Ac
timeFrame: 104 weeks after randomisation
measure: Metabolic health - insulin
timeFrame: 104 weeks after randomisation
measure: Metabolic health - HOMA2-IR
timeFrame: 104 weeks after randomisation
measure: Metabolic health - lipids
timeFrame: 104 weeks after randomisation
measure: Metabolic health - eGFR
timeFrame: 104 weeks after randomisation
measure: Metabolic health - hsCRP
timeFrame: 104 weeks after randomisation
measure: Metabolic health - Fib4
timeFrame: 104 weeks after randomisation
measure: Metabolic health - proteinuria
timeFrame: 104 weeks after randomisation
measure: Metabolic health - TSH
timeFrame: 104 weeks after randomisation
measure: Mental health - MDI
timeFrame: 104 weeks after randomisation
measure: Mental health - WBIS-M
timeFrame: 104 weeks after randomisation
measure: Mental health - EDE-Q
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: Genetic profiles' (using comprehensive genetic mapping) association with the metabolic and/or weight loss response to IWL vs usual care
timeFrame: 104 weeks after randomisation
measure: Health economy: Within-trial cost-effectiveness analysis - quality of life, index score
timeFrame: 104 weeks after randomisation
measure: Health economy: Within-trial cost-effectiveness analysis - quality of life, VAS
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 effects - incident cancer
timeFrame: 5, 10 and 20 years after randomisation
measure: Long-term effects - fracture risk
timeFrame: 5, 10 and 20 years after randomisation
measure: Long-term effects - health economic and labour market attachment, employment status
timeFrame: 5, 10 and 20 years after randomisation
measure: Long-term effects - health economic and labour market attachment, salary
timeFrame: 5, 10 and 20 years after randomisation
measure: Long-term effects - health economic and labour market attachment, absence
timeFrame: 5, 10 and 20 years after randomisation
measure: Long-term effects - health economic and labour market attachment, sick leave
timeFrame: 5, 10 and 20 years after randomisation
measure: Long-term effects - health economic and labour market attachment, long-term sick leave
timeFrame: 5, 10 and 20 years after randomisation
Locations:
city: Frederiksberg
country: Denmark
facility: Frederiksberg kommune: Social-, Sundheds- og Arbejdsmarkedsområdet
city: Frederiksberg
country: Denmark
facility: The Parker Institute, Copenhagen University Hospital - Bispebjerg and Frederiksberg
city: Hvidovre
country: Denmark
facility: Hvidovre kommune: Center for Sundhed og Ældre, Hvidovre Sundhedscenter, Sundhed og Forebyggelse
city: Hvidovre
country: Denmark
facility: The Department of Medicine and the Gastro Unit, Copenhagen University Hospital - Amager and Hvidovre
city: Søborg
country: Denmark
facility: Gladsaxe kommune: Social- og Sundhedsforvaltningen, Sundhed og Rehabilitering
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
city: Derby
country: United Kingdom
facility: University Hospitals of Derby and Burton NHS Foundation Trust
city: Ipswich
country: United Kingdom
facility: East of England RRDN
city: Leeds
country: United Kingdom
facility: Yorkshire and Humber RRDN (Leeds, Sheffield and Hull)
city: Powys
country: United Kingdom
facility: Powys Teaching Health Board
Study officials:
affiliation: Department of Medicine, Copenhagen University Hospital - Amager and Hvidovre
name: Carsten Dirksen
role: STUDY_CHAIR
References: