The Impact of a Moderate Carbohydrate Diet in Children With Type 1 Diabetes on Hybrid Closed-loop Therapy (COMBINE1)

The Impact of Carbohydrate Restriction on Glycemic Control in Children and Adolescents With Type 1 Diabetes Using a Hybrid Closed-loop Insulin Delivery System: a Randomized Cross-over Study

In the past, carbohydrate restriction was indicated as a treatment for people with type 1 diabetes when exogenous insulin was not available. Now it is mainly used as an added treatment for people with type 1 diabetes on top of standard insulin administration and glucose monitoring. Despite previous studies, the impact of carbohydrate restriction on glycemic control and quality of life is still not clear. Furthermore, few studies exist on carbohydrate restriction in children with type 1 diabetes and combined with the use of hybrid closed-loop insulin delivery. Therefore this study will determine the impact on glycemic control and the feasability of a moderate carbohydrate diet compared to a traditional diet in children (7-17 years) with type 1 diabetes on top of using a hybrid closed-loop system. In this randomized, crossover study, 28 children will follow a moderate carbohydrate diet (four weeks) and a traditional diet (four weeks) in randomized order. With a run-in period (two weeks) prior to the first diet and a wash-out period (six weeks) between the two diets, the children will participate in the study for a total of 16 weeks. The primary endpoint is the difference of time spent in target range (defined as a sensor glucose value between 70 and 180 mg/dL) between the four-week moderate carbohydrate diet and the four-week traditional diet.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus, Type 1
• Intervention / Treatment: Other: Moderate carbohydrate diet; Other: Traditional diet

• Study Type: Interventional
• Enrollment (Estimated): 28
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kristina Casteels, Prof; Phone Number: +3216343811; Email: kristina.casteels@uzleuven.be
• Study Contact Backup: Name: Laura Valgaerts; Phone Number: +3216343890; Email: laura.valgaerts@uzleuven.be

Study Locations

• Belgium
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • Recruiting
      • UZ Leuven
      • Contact: Kristina Casteels, Prof; Phone Number: +3216343811; Email: kristina.casteels@uzleuven.be
      • Contact: Laura Valgaerts; Phone Number: +3216343890; Email: laura.valgaerts@uzleuven.be

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Signed informed consent (ICF) (both children/adolescents and parents)
• ≥7 and ≤17 years old at moment of ICF signature
• ≥6 months type 1 diabetes diagnosis at moment of ICF signature
• ≥3 months use of the hybrid closed-loop system Medtronic MiniMedTM 780G, Tandem t:slim X2 Control-IQTM or Mylife Ypsopump with CamAPS algorithm at moment of ICF signature
• Ability to understand, read, write and speak Dutch, French or English at moment of ICF signature

Exclusion Criteria:

• <7 or >17 years old at moment of ICF signature
• <6 months type 1 diabetes diagnosis at moment of ICF signature
• <3 months use of the advanced hybrid closed-loop system Medtronic MiniMedTM 780G, Tandem t:slim X2 Control-IQTM or Mylife Ypsopump with CamAPS algorithm at moment of ICF signature
• Any other insulin therapy than advanced hybrid closed-loop system Medtronic MiniMedTM 780G , Tandem t:slim X2 Control-IQTM or Mylife Ypsopump with CamAPS algorithm at moment of ICF signature
• Failure to understand, read, write or speak Dutch, French or English at moment of ICF signature

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: 1st Traditional diet, 2nd Moderate carbohydrate diet; The group that starts with the traditional diet in the first 4-week diet period. After wash-out, this group will start with the moderate carbohydrate diet in the second 4-week diet period.	Other: Moderate carbohydrate diet; During the moderate carbohydrate diet, participants will be asked to limit his/her carbohydrate intake to no more than 30% of their total energy intake.; Other: Traditional diet; During the traditional diet, participants do not follow any diet, however their carbohydrate intake must be at least 50% of their total energy intake.
Experimental: Group 2: 1st Moderate carbohydrate diet, 2nd Traditional diet; The group that starts with the traditional diet in the first 4-week diet period. After wash-out, this group will start with the moderate carbohydrate diet in the second 4-week diet period.	Other: Moderate carbohydrate diet; During the moderate carbohydrate diet, participants will be asked to limit his/her carbohydrate intake to no more than 30% of their total energy intake.; Other: Traditional diet; During the traditional diet, participants do not follow any diet, however their carbohydrate intake must be at least 50% of their total energy intake.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time in range	Difference of time spent in range (70-180 mg/dL) between the moderate carbohydrate diet and the traditional diet.	4 weeks moderate carbohydrate diet and 4 weeks traditional diet

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time in tight range	Difference of time spent in range (70-140 mg/dL) between the moderate carbohydrate diet and the traditional diet.	4 weeks moderate carbohydrate diet and 4 weeks traditional diet
Time below range	Difference of time spent below range (<70 mg/dL) between the moderate carbohydrate diet and the traditional diet.	4 weeks moderate carbohydrate diet and 4 weeks traditional diet
Time in level 2 hypoglycemia	Difference of time spent below range of 54 mg/dL between the moderate carbohydrate diet and the traditional diet.	4 weeks moderate carbohydrate diet and 4 weeks traditional diet
Time above range	Difference of time spent above range (>180 mg/dL) between the moderate carbohydrate diet and the traditional diet.	4 weeks moderate carbohydrate diet and 4 weeks traditional diet
Time in level 2 hyperglycemia	Difference of time spent above range of 250 mg/dL between the moderate carbohydrate diet and the traditional diet.	4 weeks moderate carbohydrate diet and 4 weeks traditional diet
Hemoglobin A1c	Difference of hemoglobin A1c between the moderate carbohydrate diet and the traditional diet.	4 weeks moderate carbohydrate diet and 4 weeks traditional diet
Mean blood glucose	Difference of mean blood glucose between the moderate carbohydrate diet and the traditional diet.	4 weeks moderate carbohydrate diet and 4 weeks traditional diet
Glycemic variability: standard deviation and coefficient of variation	Difference of glycemic variability, in terms of standard deviation (SD) and coefficient of variation (CV) of blood glucose levels between the moderate carbohydrate diet and the traditional diet.	4 weeks moderate carbohydrate diet and 4 weeks traditional diet
Daily insulin dose	Difference of insulin doses (total, basal and bolus) between the moderate carbohydrate diet and the traditional diet.	4 weeks moderate carbohydrate diet and 4 weeks traditional diet
Number of severe hypoglycemic events	Difference in the frequency of severe hypoglycemic events between the moderate carbohydrate diet and the traditional diet.	4 weeks moderate carbohydrate diet and 4 weeks traditional diet
Number of diabetic ketoacidosis	Difference in the frequence of diabetic ketoacidosis between the moderate carbohydrate diet and the traditional diet.	4 weeks moderate carbohydrate diet and 4 weeks traditional diet
Body weight	Difference in body weight between the moderate carbohydrate diet and the traditional diet.	4 weeks moderate carbohydrate diet and 4 weeks traditional diet
Body mass index	Difference in body mass index between the moderate carbohydrate diet and the traditional diet.	4 weeks moderate carbohydrate diet and 4 weeks traditional diet
Blood lipids (total cholesterol, triglycerides, high density lipoprotein and low density lipoprotein concentrations)	Difference in blood lipids (total cholesterol, triglycerides, high density lipoprotein and low density lipoprotein concentrations) between the moderate carbohydrate diet and the traditional diet.	4 weeks moderate carbohydrate diet and 4 weeks traditional diet
Satisfaction with the diet in the context of diabetes treatment	Difference in the satisfaction with the diet (Diabetes treatment satisfaction questionnaire - DTSQs) between the moderate carbohydrate diet and the traditional diet. The DTSQs has a scale of 0-48 and a higher score is associated with a higher treatment satifaction.	4 weeks moderate carbohydrate diet and 4 weeks traditional diet
Bioelectrical impedance analysis	Difference in bioelectrical impedance analysis between the moderate carbohydrate diet and the traditional diet.	4 weeks moderate carbohydrate diet and 4 weeks traditional diet
Carb ratio	Difference in carb ratio between the moderate carbohydrate diet and the traditional diet.	4 weeks moderate carbohydrate diet and 4 weeks traditional diet
Active insulin time	Difference in active insulin time between the moderate carbohydrate diet and the traditional diet.	4 weeks moderate carbohydrate diet and 4 weeks traditional diet
Number of people who use glucose target 100 mg/dL, 110 mg/dL and 120 mg/dL	Difference in umber of people who use glucose target 100 mg/dL, 110 mg/dL and 120 mg/dL between the moderate carbohydrate diet and the traditional diet.	4 weeks moderate carbohydrate diet and 4 weeks traditional diet
Consumed carbohydrates	Difference in consumed carbohydrates between the moderate carbohydrate diet and the traditional diet.	4 weeks moderate carbohydrate diet and 4 weeks traditional diet
Meal composition	Difference in meal composition a between the moderate carbohydrate diet and the traditional diet.	4 weeks moderate carbohydrate diet and 4 weeks traditional diet

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Investigators: Principal Investigator: Kristina Casteels, Prof, UZ Leuven

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: August 14, 2024
• First Submitted That Met QC Criteria: August 20, 2024
• First Posted (Actual): August 22, 2024

Study Record Updates

• Last Update Posted (Actual): August 22, 2024
• Last Update Submitted That Met QC Criteria: August 20, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: S68499

Drug and device information, study documents

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