Manchester Intermittent Diet in Gestational Diabetes Acceptability Study

Study Overview
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Brief Summary
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A two-arm non-blinded randomised feasibility protocol trial designed to assess the feasibility, safety, and acceptability of an intermittent low energy diet (ILED) vs best National Health Service (NHS) care in women with gestational diabetes and obesity in Greater Manchester.

Detailed Description
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Overall aim: The aim of this trial is to test the safety, feasibility, and acceptability of an ILED in GDM to inform a future large-scale RCT. Background: Up to 16% of pregnant women in the United Kingdom develop GDM with rising rates due to increasing rates of obesity and maternal age. GDM affects both maternal and neonatal outcomes and is a high burden to patients and the NHS through frequent clinic visits, monitoring, and costly medications such as insulin. The National Institute for Health and Care Excellence (NICE) guidelines advocate healthy diet (with increased physical activity [PA]) as first-line therapy for GDM with approximately 30% progressing to metformin and/or insulin treatment. Our Patient and Public Involvement and Engagement work demonstrates that women with GDM are keen for alternative dietary interventions to reduce their need for medications. It has been shown that intermittent low energy diets improve glycaemic control in type-2 diabetes. The investigators wish to test the utility of ILED in GDM. Primary Aim: to test the safety, feasibility, and acceptability of an ILED in GDM to inform a future large-scale RCT. Primary Objectives: Uptake rate Recruitment rate Retention rate Adherence to the dietary interventions Completion of self-assessed glucose and ketone readings Safety outcomes: Percentage of women following ILED/best NHS care with hypoglycaemia (episodes of blood glucose of <3.0mmol/mol) Percentage of women who develop significant ketonaemia in both groups (defined as ≥1.0mmol/L) Percentage of neonatal hypoglycaemic episodes requiring intervention, neonatal birth weight, gestational age at delivery, hyperbilirubinaemia/jaundice, and/or admission to Special Care Baby Unit or neonatal intensive care, and stillbirths The incidence and rate of other adverse events (e.g. headaches, lethargy, constipation, or complications requiring hospital admission) between the start of the trial intervention and delivery. Secondary outcomes Completeness of collection of trial endpoints Fidelity of delivery of the interventions Qualitative analysis of the acceptability and implementation of the interventions Exploratory outcomes The following outcomes will be explored without statistical inference. Maternal outcomes: The percentage of women requiring metformin and/or insulin Four-point capillary glucose profiles during third trimester Change in fasting blood test results between baseline measurements, 36-37 weeks' gestation, and 12 weeks post-delivery Mode of delivery, development of preeclampsia, polyhydramnios (maximum liquor volume pool depth ≥8 cm) Quality of life and health status questionnaires (WHOQoL-BREF and SF-36 questionnaires) Foetal outcomes: Foetal weight Gestational age at delivery Method: We aim to recruit 48 women with GDM diagnosed between 24-30 weeks gestation from antenatal clinics at Wythenshawe and St Mary's hospitals, Manchester Foundation Trust, over 13 months starting in November 2022. Participants will be randomised (1:1) to ILED (2 low-energy diet days/week of 1000kcal and 5 days/week of the best NHS care healthy diet and physical activity advice) or best NHS care 7 days/week until delivery of their baby. Primary outcomes include uptake and retention of participants to the trial, and adherence to both dietary interventions. Safety outcomes will include birthweight, gestational age at delivery, neonatal hypoglycaemic episodes requiring intervention, neonatal hyperbilirubinaemia, admission to special care baby unit or neonatal intensive care unit, stillbirths, the percentage of women with hypoglycaemic episodes requiring third-party assistance, and significant maternal ketonaemia (defined as ≥1.0mmol/L) Secondary outcomes will assess the fidelity of delivery of the interventions, and qualitative analysis of participant and healthcare professionals' experiences of the diet. Exploratory outcomes include the number of women requiring metformin and/or insulin. Qualitative evaluation: Investigators will undertake qualitative analysis of the experiences and thoughts of approximately 5 participants per group and healthcare professionals delivering the interventions. Anticipated impact and dissemination: This study will inform the feasibility and design of a definitive RCT of ILED versus best NHS care in GDM. Findings will be disseminated to health professionals and patients through published articles, conference presentations and patient networks in collaboration with the patient and public involvement and engagement panel.

Official Title
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MIDDAS-GDM: A Two-Arm Randomised Feasibility Protocol Trial of an Intermittent Low-Energy Diet (ILED) in Women With Gestational Diabetes and Obesity in Greater Manchester

Conditions
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Gestational Diabetes, Gestational Diabetes Mellitus in Pregnancy, Intermittent Fasting, Pregnancy Related, Diabetes, Diabetes in Pregnancy

Intervention / Treatment
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* Other: Best NHS Care
* Other: Intermittent Low Energy Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women ≥18 years BMI of ≥27.5kg/m2 or a BMI ≥25 kg/m2 in high risk minority ethnic group (i.e. South Asian, Black African, African Caribbean) and <50 kg/m2 at booking appointment (8-12 weeks' gestation) Newly diagnosed GDM according to local diagnostic criteria (fasting glucose ≥5.3mmol/l and/or 2-hour postprandial glucose ≥8.5mmol/l in a 75g OGTT) scheduled to receive first line diet and physical activity (best NHS care) 24-30 weeks pregnant at screening appointment Exclusion Criteria: Pregestational type 1 or type 2 diabetes. Fasting glucose of ≥7 or 2-hour postprandial of ≥11 on OGTT (immediate intervention with medication would be required in this group of women) Current multiple pregnancy Maturity Onset Diabetes of the Young (MODY) Significant comorbid disease that in PI's opinion would preclude participation in the study e.g. chronic kidney disease, significant cardiac disease, history of disordered eating or severe psychological problems. Current participation in a GDM medication treatment trial People who are not capable of providing informed consent or adhering to the monitoring and safety protocols People who have previously had bariatric surgery for weight loss including gastric bypass and sleeve gastrectomy, and/or those prescribed weight loss medications (e.g. orlistat). Medications at the time of the OGTT that may interfere with results (e.g. high dose oral steroids, immunosuppressants) Previous history of intrauterine growth restriction Women who have lost more than 5% of their weight from booking appointment to screening appointment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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
Interventional Model Description: Randomised two-arm feasibility trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Best NHS Care<br>Best National Health Service (NHS) Care | Other: Best NHS Care<br>* Personalised advice and support from a diabetes dietician to follow NICE healthy eating diet and physical activity recommendations for GDM.<br>|
| Experimental: Intermittent Low Energy Diet<br>Intermittent Low Energy Diet | Other: Intermittent Low Energy Diet<br>* Two non-consecutive days of a food based 1000 kcal diet and five days of the NICE healthy eating diet and physical activity recommendations for the best NHS care group.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trial recruitment rate | Uptake to trial will be measured as a percentage of eligible participants who consent to participate in the trial per month. | Duration of trial (68 weeks) | 
| Retention to the trial | Retention rate will be measured as the percentage of participants who complete all scheduled 8 visits. | Duration of trial (68 weeks) | 
| Trial uptake | Trial uptake will be measured as the percentage of eligible participants who consent to participate in the trial. | Duration of trial (68 weeks) | 
| Adherence to the interventional intermittent low-calorie diet over course of study | Self-reported adherence to the two potential low-calorie days per week expressed as a percentage of the potential low-calorie days in the intermittent low energy diet group. | From randomisation (at 24-30 weeks' gestation) to delivery. | 
| Adherence to capillary glucose and ketone measurements over course of study | The number of self-assessed glucose (4 times a day) and ketone (3 times a day on two days of the week) measurements in both groups over the course of the study. | From randomisation (at 24-30 weeks' gestation) to delivery | 
| Episodes of hypoglycaemia requiring intervention | The percentage of women with self-reported hypoglycaemia (capillary blood glucose of <3.0 mmol/l) will be measured and compared between groups. | From 24-30 weeks' gestation until delivery. | 
| Episodes of ketonaemia requiring intervention | The percentage of women with self-reported significant ketonaemia (capillary ketones >1 mmol/l) will be measured and compared between groups. | From 24-30 weeks' gestation until delivery. | 
| Rates of neonatal hyperbilirubinaemia/jaundice | Percentage of neonatal hyperbilirubinaemia/jaundice (defined as a total serum bilirubin level above 86 μmol/l) episodes will be recorded in both groups. | From delivery until final visit at 12-13 weeks' postpartum | 
| Rates of neonatal hypoglycaemia | Percentage of neonatal hypoglycaemic episodes requiring intervention (blood glucose checked 2-hours post delivery and 2-hours thereafter for 12 hours) will be recorded in both groups. | From delivery until 12 hours post-delivery | 
| Neonatal birthweight | Neonatal birth weight will be measured in kilograms and recorded in both groups. | At delivery | 
| Neonatal gestational age at delivery | Gestational age at delivery will be measured in weeks and recorded in both groups. | At delivery | 
| Gestational age at delivery | Gestational age at delivery in weeks will be recorded in both groups. | At delivery | 
| Rates of admission to special care baby unit or neonatal intensive care | Rates of admission to Special Care Baby Unit or Neonatal Intensive Care will be recorded in both groups. | From delivery until final visit at 12-13 weeks' postpartum | 
| Number of stillbirths | Number of stillbirths will be recorded in both groups. | At delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of completed scheduled patient contacts | Completion of scheduled patient contacts with the trial dietitian and gestational diabetes midwife will be recorded and compared between groups. | Duration of trial (68 weeks) | 
| Completion rates of food diaries | Participants will be asked to complete 4-day food diaries for 4 weeks of the trial at 24-28 weeks' gestation, 34-35 weeks' gestation, 36-37 weeks' gestation, and 12-13 weeks postpartum. They will also be given the option of recording diaries during the other weeks as this may help with their adherence. Completion rates of the food diaries each week across the whole intervention as a percentage of weeks in both groups will inform the utility of food diaries for tracking diet behaviour in both groups | 4 day food diaries at 24-30 weeks' gestation, 34-35 weeks' gestation, 36-37 weeks' gestation, and 12-13 weeks postpartum. | 
| Completion rates of International Physical Activity Questionnaire (IPAQ) | Participants will be asked to complete the IPAQ during 4 weeks of the trial at 24-28 weeks' gestation, 34-35 weeks' gestation, 36-37 weeks' gestation, and 12-13 weeks postpartum. Completion rates will be measured as a percentage of weeks completed in both groups. | IPAQ questionnaire at 24-30 weeks' gestation, 34-35 weeks' gestation, 36-37 weeks' gestation, and 12-13 weeks postpartum. | 
| The acceptability of the dietary interventions will be explored qualitatively | A subset of participants in both groups (approximately 5 participants from each group) will be invited to an optional qualitative substudy which will involve one semi-structured interview at the end of the intervention. Participants will be asked about their experiences and thoughts regarding the intervention. Key themes will be identified using Braun and Clarke's thematic analysis to identify key issues around the acceptability of the test intervention. | 12-13 weeks' postpartum |