Intensive Weight Loss Intervention Versus Usual Care for Adults With Severe and Complex Obesity (LightWAY)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Obesity
• Intervention / Treatment: Behavioral: Usual care; Behavioral: Intensive weight loss intervention

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.

• Study Type: Interventional
• Enrollment (Estimated): 600
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Carsten Dirksen, Ass. Prof.; Phone Number: +45 29425320; Email: carsten.dirksen@regionh.dk
• Study Contact Backup: Name: Susan Jebb, Professor; Phone Number: +44 (0) 1865 617 831; Email: lightcom@phc.ox.ac.uk

Study Locations

• Denmark
  • Frederiksberg, Denmark, 2000
    • Not yet recruiting
    • Frederiksberg kommune: Social-, Sundheds- og Arbejdsmarkedsområdet
    • Contact: Addie J Frederiksen
  • Frederiksberg, Denmark, 2000
    • Not yet recruiting
    • The Parker Institute, Copenhagen University Hospital - Bispebjerg and Frederiksberg
    • Contact: Sofus C Larsen
  • Hvidovre, Denmark, 2650
    • Recruiting
    • The Department of Medicine and the Gastro Unit, Copenhagen University Hospital - Amager and Hvidovre
    • Contact: Carsten Dirksen
  • Hvidovre, Denmark, 2650
    • Not yet recruiting
    • Hvidovre kommune: Center for Sundhed og Ældre, Hvidovre Sundhedscenter, Sundhed og Forebyggelse
    • Contact: Maria Bleiback Clausen
  • Søborg, Denmark, 2860
    • Not yet recruiting
    • Gladsaxe kommune: Social- og Sundhedsforvaltningen, Sundhed og Rehabilitering
    • Contact: Julie Borgen Braget
• United Kingdom
  • Oxford, United Kingdom
    • Not yet recruiting
    • IHR CRN: Thames Valley and South Midlands
    • Contact: Susan Jebb

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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, coeliac disease, 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intensive weight loss intervention; The intensive weight loss intervention (IWL) includes total dietary replacements, behavioural support, and weight loss medication. The intervention consists of three phases: induction, weight loss continuation, maintenance, and it will lasts two years in total.	Behavioral: Intensive weight loss intervention; Intensive weight loss intervention, incl. total meal replacements, behavioural support, and weight loss medication.
Active Comparator: Usual care; Denmark: usual care offered by the GP or local municipality. The UK: tier 3 weight management services.	Behavioral: Usual care; Usual care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight	Weight (kg)	104 weeks after randomisation
MetS-Z	Metabolic syndrome severity Z-score (scale from -4 to 4, mean is 0, higher scores indicate a worse outcome)	104 weeks after randomisation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gait speed	4-metre gait speed (m/s)	104 weeks after randomisation
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
Weight loss (20%)	Proportion of participants with weight loss ≥20%	104 weeks after randomisation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Labour market attachment - days of sick leave	Self-reported number of days sick leave during follow-up	104 weeks after randomisation
Health economy: Within-trial cost-effectiveness analysis - costs	24-month costs, DKK	104 weeks after randomisation
Health economy: Within-trial cost-effectiveness analysis - QALY	Incremental cost per quality-adjusted-life-year (QALY) gained, DKK	104 weeks after randomisation
Health economy: Model-based cost-effectiveness analysis - QALY	Predicted lifetime QALYs gained	104 weeks after randomisation
Health economy: Model-based cost-effectiveness analysis - healthcare costs	Predicted lifetime healthcare costs, DKK	104 weeks after randomisation
Health economy: Model-based cost-effectiveness analysis - cost effectiveness ratios	Long-term incremental cost effectiveness ratios	104 weeks after randomisation
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
SAE	Proportion of participants with at least one serious adverse event during the intervention period (according to ICH-GCP guidelines)	104 weeks after randomisation
Incident eating disorders	Proportion of participants with incident eating disorders during the intervention period	104 weeks after randomisation
Body composition - waist circumference	Waist circumference (cm)	104 weeks after randomisation
Body composition - fat percentage	Body fat percentage; Visceral fat percentage; Subcutaneous fat percentage	104 weeks after randomisation
Body composition - weight loss (10%)	Proportion of participants with weight loss ≥10%	104 weeks after randomisation
Physical functioning - SENS	Objectively measured moderate to vigorous physical activity (MVPA) using SENS Motion accelerometers (hours/day)	104 weeks after randomisation
Physical functioning - SF-36	Short Form 36 (SF-36) physical component score (scale from 0-100, higher scores indicate better physical health)	104 weeks after randomisation
Physical functioning - sit to stand test	Number of sit to stands completed in the 30 Second Sit to Stand test	104 weeks after randomisation
Sleep	Sleep duration using SENS Motion accelerometers (hours/day)	104 weeks after randomisation
Medications during the intervention period	Proportion of participants prescribed glucose-lowering medications (number, type); Proportion of participants prescribed lipid-lowering medications (number, type); Proportion of participants prescribed blood pressure-lowering medications (number, type); Proportion of participants prescribed medication for pain relief (number, type); Proportion of participants prescribed use of medications for psychiatric disorders (number, type)	104 weeks after randomisation
Metabolic health - blood pressure	Systolic and diastolic blood pressure (mmHg)	104 weeks after randomisation
Metabolic health - pulse	Pulse rate (beats per minute)	104 weeks after randomisation
Metabolic health - Hb1Ac	Haemoglobin A1c (mmol/mol)	104 weeks after randomisation
Metabolic health - insulin	Fasting insulin concentration (pmol/L)	104 weeks after randomisation
Metabolic health - HOMA2-IR	HOMA2-IR (calculated from glucose and C-peptide concentration) (ratio)	104 weeks after randomisation
Metabolic health - lipids	Fasting lipid profile (HDL, LDL and triglycerides) (mmol/L)	104 weeks after randomisation
Metabolic health - eGFR	Estimated Glomerular Filtration Rate (eGFR), creatinine (µmol/L), calculated from creatinine, sex and years	104 weeks after randomisation
Metabolic health - hsCRP	High-sensitivity C-reactive protein (hsCRP), mg/L	104 weeks after randomisation
Metabolic health - Fib4	Fib-4 (ALT/AST/platelets) (ratio)	104 weeks after randomisation
Metabolic health - proteinuria	Proteinuria, measured as urine albumin/creatinine (ratio)	104 weeks after randomisation
Metabolic health - TSH	Thyroid-stimulating hormone (IU/L)	104 weeks after randomisation
Mental health - MDI	Major Depression Inventory (MDI) (scale from 0-50, higher scores indicate more symptoms of depression)	104 weeks after randomisation
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
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
Genetic profiles' (using comprehensive genetic mapping) association with the metabolic and/or weight loss response to IWL vs usual care	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
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
Long-term effects - 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
Long-term effects - fracture risk	Proportion of participants with major osteoporotic fracture (hip, spine, wrist); Proportion of participants with any fracture	5, 10 and 20 years after randomisation
Long-term effects - health economic and labour market attachment, employment status	Employment status for each participant	5, 10 and 20 years after randomisation
Long-term effects - health economic and labour market attachment, salary	Salary for each participant	5, 10 and 20 years after randomisation
Long-term effects - health economic and labour market attachment, absence	Number of absence days	5, 10 and 20 years after randomisation
Long-term effects - health economic and labour market attachment, sick leave	Proportion of participants with any sick leave	5, 10 and 20 years after randomisation
Long-term effects - 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
Bone mineral density (BMD) assessed by DXA	Bone mineral density (g/cm²) of hip (total hip and femoral neck),; Bone mineral density (g/cm²) of lumbar region	104 weeks after randomisation
Health economy: Within-trial cost-effectiveness analysis - quality of life, index score	Quality of life (measured using the 5-level EQ-5D version, EQ-5D-5L index score (score between -1 and 1, higher scores indicate better health)	104 weeks after randomisation
Health economy: Within-trial cost-effectiveness analysis - quality of life, VAS	Quality of life (measured using the 5-level EQ-5D version, EQ-5D-5L VAS score (scale from 0-100, higher scores indicate better health)	104 weeks after randomisation

Collaborators and Investigators

• Sponsor: Carsten Dirksen
• Collaborators: University of Copenhagen; University of Oxford; University of Bristol; University of Southern Denmark; Copenhagen Trial Unit, Center for Clinical Intervention Research
• Investigators: Study Chair: Carsten Dirksen, Department of Medicine, Copenhagen University Hospital - Amager and Hvidovre

Publications and helpful links

Helpful Links

• LightCOM website

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2048

Study Registration Dates

• First Submitted: March 13, 2024
• First Submitted That Met QC Criteria: March 19, 2024
• First Posted (Actual): March 20, 2024

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Body Weight Changes; Obesity; Weight Loss
• Other Study ID Numbers: LightWAY

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After the results have been published, the aim is to make a depersonalised dataset publicly available on e.g. ClinicalTrials.gov and/or the European Union (EU) Zenodo database (https://zenodo.org/). The final choice will reflect which platform(s) that are compliant with current legislation at that time.
• IPD Sharing Time Frame: When the results have been published
• IPD Sharing Access Criteria: Researchers with a protocol for their planned study
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No