Clinical trial NCT05899166: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Diabetes Mellitus, Type 1
Keywords: carbohydrate reduced
low-carb
diabetes
keto
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
Collaborators: name: University of South Florida
name: Indiana University
First posted: 2023-06-12
Enrollment: 52
Sex: ALL
Minimum age (years): 5
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

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.

Primary outcomes:
measure: Decline in Beta-cell Function
timeFrame: Change over 1, 5, and 9 months, corrected for baseline
Secondary outcomes:
measure: Time in Range (TIR) 70-180 mg/dl
timeFrame: Over 9 months and optional at 24 months
measure: Duration of Clinical Diabetes Remission
timeFrame: 1, 5, 9, and optional at 24 months
measure: Time in low Range (TIR) <70 mg/dl
timeFrame: Over 9 months and optional at 24 months
measure: Time in very low Range (TIR) <55 mg/dl
timeFrame: Over 9 months and optional at 24 months
measure: Time in high Range (TIR) >180 mg/dl
timeFrame: Over 9 months and optional at 24 months
measure: Time in very high Range (TIR) >250 mg/dl
timeFrame: Over 9 months and optional at 24 months
measure: Average Blood Glucose
timeFrame: Over 9 months and optional at 24 months
measure: Coefficient of Glycemic Variation (CV)
timeFrame: Over 9 months and optional at 24 months
measure: Mean Amplitude of Glycemic Excursions (MAGE)
timeFrame: Over 9 months and optional at 24 months
measure: Total Daily Insulin Dose
timeFrame: Over 9 months and optional at 24 months
measure: HOMA-IR (Homeostatic Model Assessment for Insulin Resistance)
timeFrame: 1, 5, 9, and optional at 24 months
measure: BMI
timeFrame: 1, 5, 9, and optional at 24 months
measure: Lipid panel
timeFrame: 1, 5, 9, and optional at 24 months
measure: HDL to Triglyceride Ratio
timeFrame: 1, 5, 9, and optional at 24 months
measure: Lipoprotein Subfractions
timeFrame: 1, 5, 9, and optional at 24 months
measure: Inflammasome, targeted
timeFrame: 1, 5, 9, and optional at 24 months
measure: Microbiome, targeted and untargeted
timeFrame: 1, 5, 9, and optional at 24 months
measure: Metabolome, targeted and untargeted
timeFrame: 1, 5, 9, and optional at 24 months
measure: Problem Areas in Diabetes (PAID-Ped) - child
timeFrame: 1, 5, 9, and optional at 24 months
measure: Problem Areas in Diabetes (PAID-PR) - parent
timeFrame: 1, 5, 9, and optional at 24 months
measure: Pediatric Quality of Life (PEDSQL) General Module - parent
timeFrame: 1, 5, 9, and optional at 24 months
measure: Pediatric Quality of Life (PEDSQL) General Module - child
timeFrame: 1, 5, 9, and optional at 24 months
measure: Pediatric Quality of Life (PEDSQL) Diabetes Module - parent
timeFrame: 1, 5, 9, and optional at 24 months
measure: Pediatric Quality of Life (PEDSQL) Diabetes Module - child
timeFrame: 1, 5, 9, and optional at 24 months
measure: Child Eating Disorder Examination Questionnaire (ChEDE-Q8)
timeFrame: 1, 5, 9, and optional at 24 months
measure: Perceptions on Diet Management of Diabetes
timeFrame: 1, 5, 9, and optional at 24 months
measure: Qualitative patient perspectives, interview - parent
timeFrame: optional at 9 months
measure: Qualitative patient perspectives, interview - child
timeFrame: optional at 9 months
Other outcomes:
measure: Time in tight Range (TIR) 70-140 mg/dl
timeFrame: Over 9 months and optional at 24 months
measure: Time above tight Range (TIR) >140 mg/dl
timeFrame: Over 9 months and optional at 24 months
measure: BOHB (beta-hydroxybutyrate), fasting blood concentration
timeFrame: Over 9 months and optional at 24 months
measure: Growth
timeFrame: 1, 5, 9, and optional at 24 months
measure: Growth velocity
timeFrame: 1, 5, 9, and optional at 24 months
measure: Weigh-gain
timeFrame: 1, 5, 9, and optional at 24 months
measure: Confirmed Ketoacidosis
timeFrame: Over 9 months and optional at 24 months
measure: Severe Hypoglycemia
timeFrame: Over 9 months and optional at 24 months
measure: Diabetes Related Emergency Visits
timeFrame: Over 9 months and optional at 24 months
measure: Diabetes Related Hospitalizations
timeFrame: Over 9 months and optional at 24 months
measure: Study termination for disordered eating
timeFrame: Over 9 months
measure: Study termination for growth deceleration
timeFrame: Over 9 months
measure: Study termination for dyslipidemia
timeFrame: Over 9 months
Locations:
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
Study officials:
affiliation: Boston Children's Hospital
name: Belinda Lennerz
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.