ARIADNE: A Study of Weight Loss for Diabetes Treatment and Wellbeing

Study Overview
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Brief Summary
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The NHS has started a trial-run of a weight loss programme replacing food with 800-calorie shakes and soups for 3 months, offered to people with newly diagnosed type 2 diabetes (T2D) to lose weight and put their diabetes into remission. Some healthcare professionals and charities are sceptical about the programme's effect on people's mental health. They fear it may trigger people to have a negative relationship with food (disordered eating). Some studies show indirectly that these programmes are somewhat safe; however it is not known for sure if it could affect people's relationship with food for the worse. Investigators will invite 56 people with T2D and disordered eating (picked up by questionnaires they will fill in) to participate in a trial. Of these participants, 28 will get TDR and the rest will get their standard care. Investigators will then measure how their scores of disordered eating change at 1, 3, 4, 6 and 12 months. Investigators also plan to analyse the recorded sessions to better understand participants' experiences using TDR and their thoughts about eating and body image. This study will help shed light on how safe this type of diet is for people with disordered eating. It may lead to screening for eating disorders if TDR becomes standard care. If concerns are unfounded, it can reassure people with type 2 diabetes and healthcare professionals.

Official Title
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The Impact of Low-energy totAl Diet Replacement With Behavioural Support for remIssion of Type 2 DIAbetes on disordEred eatiNg: the ARIADNE Randomised Non-inferiority Controlled Trial

Conditions
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Type2diabetes, Disordered Eating, Obesity, Overweight and Obesity, Diet Habit

Intervention / Treatment
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* Behavioral: Low calorie total diet replacement
* Other: Usual care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to give informed consent, can communicate in English Age between 18 and 65 years inclusive Live in England BMI ≥27 kg/m2 or higher (adjusted to ≥25 kg/m2 for people of Black, Asian and minority ethnic origin) Diagnosed with T2D within 6 years prior to the day of screening Global EDE-Q scores ≥2.67 To have an HbA1c taken in the last 12 months Latest HbA1c ≥43 mmol/mol (6.1%) and ≤87 mmol/mol (10%) if on diabetes medication OR latest hbA1c ≥ 48 mmol/mol (6.5%) and ≤87 mmol/mol (10%), if not on diabetes medication. If diagnosed with type 2 diabetes more than 1 year since day of screening, the participant must have attended their GP surgery for monitoring/ diabetes review when last offered Commit to continue annual reviews with their GP, even if T2D remission is achieved Exclusion Criteria: The participant must not enter the study if ANY of the following apply: Current or previous clinical diagnosis of an eating disorder Combination of EDE-Q ≥4 AND a CIA score ≥16 at screening Currently participating in a structured weight loss programme or self-reporting that they have lost >10% of their body weight in the last 3 months Insulin use Known kidney disease of stage 3/4/5 or eGFR <60 mls/min/1.73 m2 within the last 12 months Active substance use disorder Active cancer other than skin cancer Known proliferative retinopathy that has not been treated Porphyria Undergone or is awaiting bariatric surgery Myocardial infarction or stroke within previous 6 months Severe heart failure defined as equivalent to the New York Heart Association (NYHA) grade 3 or 4 Active liver disease (not including non-alcoholic fatty liver disease) Pregnant, breastfeeding, or planning to become pregnant during the course of the study Soy or milk or fish allergy, lactose intolerance, or following a vegan diet People currently participating in another study or clinical trial of a CTIMP/non-CTIMP

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention- Low calorie diet/ Total diet replacement<br>Participants in the intervention group will be offered a dietitian-delivered intervention over 6 months, similar to the NHS pilot of low calorie diets for type 2 diabetes remission. The intervention starts with 12 weeks of low-energy total diet replacement (approx. 860 kcal/day) in a nutritionally replete package of soups, shakes, and bars. It continues with stepped food reintroduction (maximum 6 weeks) as a low-calorie, nutrient-rich diet personalised to the individual participant circumstances and preferences, and weight maintenance (6 weeks). | Behavioral: Low calorie total diet replacement<br>* Summary Weeks 1-12: TDR phase Weeks 13-14: Food reintroduction phase I Weeks 15-16: Food reintroduction phase II Weeks 17 till 20: Food reintroduction phase III Weeks 21 till 24: Maintenance phase<br>|
| Other: Control- usual care<br>Participants allocated to the control group will be offered and continue benefiting from standard care. Participants will not be stopped from pursuing any behavioural weight management programme but if they do, this will be recorded. Participants will be offered an invitation to a 30-45' 1:1 session with the research dietitian at the end of the study to provide help and signposting as required for the management of their diabetes. | Other: Usual care<br>* Participants allocated to the control group will be offered and continue benefiting from standard care. Participants will not be stopped from pursuing any behavioural weight management programme but if they do, this will be recorded.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global score of disordered eating psychopathology | Between group difference in scores of disordered eating psychopathology, as measured by the global score of the self-administered Eating Disorders Examination questionnaire (EDE-Q). Scores range from 0 to 6, with higher scores indicating more severe eating disorders psychopathology. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global score of disordered eating psychopathology | Between group difference in scores of disordered eating psychopathology, as measured by the global score of the self-administered Eating Disorders Examination questionnaire (EDE-Q). Scores range from 0 to 6, with higher scores indicating more severe eating disorders psychopathology. | 4, 12, 16, and 52 weeks | 
| Subscales of disordered eating psychopathology | Between group difference in sub-scale scores of disordered eating, assessed by the subscale scores of Eating Disorders Examination questionnaire (EDE-Q): Restraint, Eating concern, Shape concern, Weight concern. Subscale scores reflect the severity of the specific characteristics of disordered eating. Higher scores in each subgroup indicate more severe psychopathology. | 4, 12, 16, 24 and 52 weeks | 
| Psychosocial impairment | Between group difference in psychosocial impairment, assessed by the self-administered clinical impairment assessment (CIA) questionnaire. The CIA measures the severity of psychosocial impairment due to eating disorder features, and scores range from o to 48, with higher scores indicating more severe impairment. | 4, 12, 16, 24 and 52 weeks | 
| Weight | Changes between group, assessed by self-weighing | 12, 24 and 52 weeks |