Carbohydrate Beta Cell Function and Glucose Control in Children With Diabetes

Boston Children's Hospital

Status: Enrolling

Conditions: Diabetes Mellitus, Type 1

Treatments: Other: Standard diet, food delivery and education; Other: Ketogenic diet, food delivery and education

Study type: Interventional

Funder types: Other

Identifiers

NCT05899166

IRB-P00044330

Details and patient eligibility

About

The goal of this clinical trial is to test the effects of a ketogenic diet on the progression and control of type 1 diabetes in children with newly diagnosed diabetes. The main questions to answer are:

• Does a ketogenic diet prolong the honeymoon period of type 1 diabetes?
• Does a ketogenic diet improve diabetes control?
• Is a ketogenic diet safe, acceptable and sustainable in children with newly diagnosed diabetes?
• What are the microbiome, inflammatory and metabolic changes linking diet to β-cell function?

Participants will receive a combination of free meals, groceries, micronutrient supplements, and intensive diet and diabetes education for 9 months.

• Diabetes care devices will be connected for cloud-based data collection.
• Bi-weekly data downloads and remote check-ins will assess dietary intake, satisfaction with diet and study procedures, and possible safety concerns.
• During four study visits held at at baseline, 1, 5, and 9 months, an intravenous catheter (IV) will be placed for collection of 5 blood samples before and up to 2 hours after a liquid test meal (protein shake) to assess insulin response. A stool sample will also be collected to assess microbiome changes.
• Children and their caregivers may be invited to participate in a semi-structured interview, and online questionnaires to assess their experience with the diet and diabetes care, general well-being and quality of life.
• Children and their caregivers may be invited to participate in a follow-up visit to evaluate long-term effects after 24 months.

Comparison will be made between a ketogenic vs standard diet.

Full description

Type I diabetes is caused by an autoimmune destruction of insulin producing β-cells in the pancreas, resulting in absolute insulin deficiency. In the first months after diagnosis, a small number of β-cells typically remain and, by producing insulin, significantly improve diabetes control and reduce disease burden.

Preliminary data suggest that this early disease stage entitled the "honeymoon period" might be extended by a ketogenic diet, which would provide a major therapeutic advantage and may reduce chronic disease burden.

To test the hypothesis that a ketogenic vs. standard diet will extend the honeymoon period and improve diabetes control in children, the researchers are conducting a study employing education and food deliveries of a ketogenic or standard diet to children and their families. Fifty-two children aged 5 to 12 years with newly diagnosed diabetes will participate. Children will be assigned by chance (randomized) to receive either a ketogenic or a standard diet for 9 months. Chances to be assigned to either diet are 50:50 like a coin flip, and 26 children will participate in each diet arm.

Participants will receive a combination of free meals, groceries, micronutrient supplements, and intensive diet and diabetes education throughout the 9 months. Continuous glucose monitoring (CGM) and diaries will be used for cloud-based data collection. Bi-weekly data downloads and remote check-ins will be performed to assess dietary intake, satisfaction with diet and study procedures, and possible safety concerns. Participants are instructed to measure blood ketone levels with their home ketone meter anytime blood glucose levels exceed a safety threshold and to call the study physician for persistent low glucose levels or ketones above diet specific safety thresholds.

Study visits are held at at baseline, 1, 5, and 9 months to collect height, weight, stool and blood samples for hormones, metabolites and inflammatory biomarkers. At each visit, an intravenous catheter (IV) will be placed to collect fasting blood samples, followed by a liquid test meal (protein shake) and collection of four additional blood samples from the IV over the course of two hours. Prior to each visit, participants will collect stool samples at home using provided kits. In addition, participants and their families may be invited to participate in a semi-structured interview, and online questionnaires to asses their food intake, experience with the diet, diabetes care burden and complications, and general well-being and quality of life. They may also be invited to participate in a follow-up visit to evaluate long-term effects after 24 months.

Enrollment: 52 estimated patients

Sex: All

Ages: 5 to 12 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Children aged 5 to 12 years.
• Within 3 month of diabetes diagnosis.
• Insulin adjusted HbA1c ≤9 if enrolled ≥ 2 months pat diagnosis.
• Type 1 diabetes confirmed by immediate insulin requirement and any 2 of the following criteria: autoimmunity marker [glutamate decarboxylase-65, islet-antigen-2, zinc transporter-8, insulin [prior to first insulin dose]; age under 10 years, BMI <95th percentile.
• Family committed and able to participate in study education and implement dietary intervention.

Exclusion criteria

• Dietary needs or habits incompatible with the study meal plans, (e.g., vegan, major food intolerances/allergies, ketogenic).
• Eating disorders as assessed by Chede-Q8.
• Major medical illness or use of medications other than insulin that could interfere with metabolic or glycemic variables.
• Major psychiatric illness.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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52 participants in 2 patient groups

ketogenic diet

Experimental group

Description:

The diet will be high in protein and healthy fats and comprise meat, fish, fibrous vegetables, nuts, dairy, and berries. Macronutrient composition will be \~ 5% carbohydrate, 20% protein, 70% fat. Participants will receive a daily multi-vitamin, magnesium supplement, and supplemental salt (bouillon cubes) to ascertain micronutrient sufficiency and help with transition to the diet.

Treatment:

Other: Ketogenic diet, food delivery and education

standard diet

Active Comparator group

Description:

The diet will be consistent with prevailing dietary guidelines and recommendations and contain meat, fish, grains, vegetables, fruit and dairy. At least 50% of grain-based products will be whole grains. Meats will be primarily lean, and dairy products will be fat-free or low-fat. Macronutrient composition will be \~50% carbohydrate (\<10% added sugars), 20% protein, 30% fat. Participants will receive a daily multi-vitamin supplement to ascertain micronutrient sufficiency.

Treatment:

Other: Standard diet, food delivery and education