Carbohydrate Beta Cell Function and Glucose Control in Children With Diabetes

NCT05899166 | Recruiting DMC

• 1 other identifier: IRB-P00044330
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Diabetes Mellitus, Type 1

Keywords

carbohydrate reduced; low-carb; diabetes; keto

Outcome Measures

Primary Outcomes (1)

• Decline in Beta-cell Function

  Change in C-peptide 2-h area under the curve after a mixed-meal tolerance test (ΔCP).

  Change over 1, 5, and 9 months, corrected for baseline

Secondary Outcomes (28)

• Time in Range (TIR) 70-180 mg/dl

  Over 9 months and optional at 24 months

• Duration of Clinical Diabetes Remission

  1, 5, 9, and optional at 24 months

• Time in low Range (TIR) <70 mg/dl

  Over 9 months and optional at 24 months

• Time in very low Range (TIR) <55 mg/dl

  Over 9 months and optional at 24 months

• Time in high Range (TIR) >180 mg/dl

  Over 9 months and optional at 24 months

Other Outcomes (13)

• Time in tight Range (TIR) 70-140 mg/dl

  Over 9 months and optional at 24 months

• Time above tight Range (TIR) >140 mg/dl

  Over 9 months and optional at 24 months

• BOHB (beta-hydroxybutyrate), fasting blood concentration

  Over 9 months and optional at 24 months

Study Arms (2)

ketogenic diet

EXPERIMENTAL

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.

Other: Ketogenic diet, food delivery and education

standard diet

ACTIVE COMPARATOR

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.

Other: Standard diet, food delivery and education

Interventions

Ketogenic diet, food delivery and education OTHER

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.

ketogenic diet

Standard diet, food delivery and education OTHER

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.

standard diet

Eligibility Criteria

• Age: 5 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Boston Children's Hospital: lead
• University of South Florida: collaborator
• Indiana University: collaborator

Study Sites (1)

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Related Publications (2)

• 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 BACKGROUND

• 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 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus

Interventions

Diet, Ketogenic; Educational Status

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Diet, Carbohydrate-Restricted; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Socioeconomic Factors; Population Characteristics

Study Officials

• Belinda Lennerz

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Belinda Lennerz, MD PhD

CONTACT

857-218-3896; belinda.lennerz@childrens.harvard.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor in Pediatrics

Study Record Dates

• First Submitted: February 1, 2023
• First Posted: June 12, 2023
• Study Start: May 31, 2024
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): April 30, 2029
• Last Updated: April 24, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Study protocol and statistical analysis plan will be shared prior to enrollment of the first participant. De-identified data will be shared upon manuscript publication.
• Access Criteria: Data will be downloadable.

Locations

US (1)