Carbohydrate Beta Cell Function and Glucose Control in Children With Diabetes

Official title

Effect of Dietary Carbohydrate on Diabetes Control and Beta Cell Function in Children With Newly Diagnosed Diabetes

Overview

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.

Detailed 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.

Interventions

• Other Ketogenic diet, food delivery and education
  Meals and groceries will be delivered and participants will receive education on nutrition, meal preparation, and diabetes care strategies. Participants will consume study-prescribed foods exclusively.
• Other Standard diet, food delivery and education
  Meals and groceries will be delivered and participants will receive education on nutrition, meal preparation, and diabetes care strategies. Participants will consume study-prescribed foods exclusively.

Primary outcome measures

• Decline in Beta-cell Function [Time frame: Change over 1, 5, and 9 months, corrected for baseline]

Secondary outcome measures (12)

• Time in Range (TIR) 70-180 mg/dl [Time frame: Over 9 months and optional at 24 months]
• Duration of Clinical Diabetes Remission [Time frame: 1, 5, 9, and optional at 24 months]
• Time in low Range (TIR) <70 mg/dl [Time frame: Over 9 months and optional at 24 months]
• Time in very low Range (TIR) <55 mg/dl [Time frame: Over 9 months and optional at 24 months]
• Time in high Range (TIR) >180 mg/dl [Time frame: Over 9 months and optional at 24 months]
• Time in very high Range (TIR) >250 mg/dl [Time frame: Over 9 months and optional at 24 months]
• Average Blood Glucose [Time frame: Over 9 months and optional at 24 months]
• Coefficient of Glycemic Variation (CV) [Time frame: Over 9 months and optional at 24 months]
• Mean Amplitude of Glycemic Excursions (MAGE) [Time frame: Over 9 months and optional at 24 months]
• Total Daily Insulin Dose [Time frame: Over 9 months and optional at 24 months]
• HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) [Time frame: 1, 5, 9, and optional at 24 months]
• BMI [Time frame: 1, 5, 9, and optional at 24 months]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

United States · 1 center

• Boston Children's Hospital — Boston

Publications

• Lennerz BS, Koutnik AP, Azova S, Wolfsdorf JI, Ludwig DS. Carbohydrate restriction for diabetes: rediscovering centuries-old wisdom. J Clin Invest. 2021 Jan 4;131(1):e142246. doi: 10.1172/JCI142246. PMID 33393511
• Lennerz BS, Barton A, Bernstein RK, Dikeman RD, Diulus C, Hallberg S, Rhodes ET, Ebbeling CB, Westman EC, Yancy WS Jr, Ludwig DS. Management of Type 1 Diabetes With a Very Low-Carbohydrate Diet. Pediatrics. 2018 Jun;141(6):e20173349. doi: 10.1542/peds.2017-3349. Epub 2018 May 7. PMID 29735574

Identifiers

NCT: NCT05899166 · IRB-P00044330

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗