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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
52
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.
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.
Boston Children's Hospital
Boston, Massachusetts, United States
RECRUITINGDecline in Beta-cell Function
Change in C-peptide 2-h area under the curve after a mixed-meal tolerance test (ΔCP).
Time frame: Change over 1, 5, and 9 months, corrected for baseline
Time in Range (TIR) 70-180 mg/dl
From continuous glucose monitoring (CGM) - percent time spent in the specified glycemic target range will be computed throughout study participation in 2-week increments.
Time frame: Over 9 months and optional at 24 months
Duration of Clinical Diabetes Remission
Calculated based on percent children with insulin dose corrected HbA1c (IDAA1c) \<9.
Time frame: 1, 5, 9, and optional at 24 months
Time in low Range (TIR) <70 mg/dl
From CGM - percent time spent in the specified glycemic target range will be computed throughout study participation in 2-week increments.
Time frame: Over 9 months and optional at 24 months
Time in very low Range (TIR) <55 mg/dl
From CGM - percent time spent in the specified glycemic target range will be computed throughout study participation in 2-week increments.
Time frame: Over 9 months and optional at 24 months
Time in high Range (TIR) >180 mg/dl
From CGM - percent time spent in the specified glycemic target range will be computed throughout study participation 2-week increments.
Time frame: Over 9 months and optional at 24 months
Time in very high Range (TIR) >250 mg/dl
From CGM - percent time spent in the specified glycemic target range will be computed throughout study participation in 2-week increments.
Time frame: Over 9 months and optional at 24 months
Average Blood Glucose
From CGM - will be computed throughout study participation in 2-week increments.
Time frame: Over 9 months and optional at 24 months
Coefficient of Glycemic Variation (CV)
From CGM - will be computed by dividing glucose standard deviation by glucose average throughout study participation in 2-week increments.
Time frame: Over 9 months and optional at 24 months
Mean Amplitude of Glycemic Excursions (MAGE)
From CGM - will be computed using published formula throughout study participation in 2-week increments.
Time frame: Over 9 months and optional at 24 months
Total Daily Insulin Dose
From insulin administration device uploads - will be computed in units per kg throughout study participation in 2-week increments.
Time frame: Over 9 months and optional at 24 months
HOMA-IR (Homeostatic Model Assessment for Insulin Resistance)
Calculated from fasting blood draw \[fasting insulin (µU/ml) × fasting plasma glucose (mg/dl)\]/405.
Time frame: 1, 5, 9, and optional at 24 months
BMI
Weight divided by height squared.
Time frame: 1, 5, 9, and optional at 24 months
Lipid panel
Fasting blood - total, LDL and HDL cholesterol, and triglycerides.
Time frame: 1, 5, 9, and optional at 24 months
HDL to Triglyceride Ratio
Fasting blood
Time frame: 1, 5, 9, and optional at 24 months
Lipoprotein Subfractions
Fasting blood
Time frame: 1, 5, 9, and optional at 24 months
Inflammasome, targeted
Interleukins 1β, 17, 23, 6, 10; high sensitivity c-reactive protein; tumor necrosis factor α, interferon gamma
Time frame: 1, 5, 9, and optional at 24 months
Microbiome, targeted and untargeted
Extraction and sequencing will be performed by Qiagen PowerSoil DNA extraction using Qiagen's DNeasy 96 PowerSoil Pro QIAcube HT Kit (480), followed by whole genome sequencing (WGS) using a miniaturized version of the NEBNext Ultra FS II method.
Time frame: 1, 5, 9, and optional at 24 months
Metabolome, targeted and untargeted
Blood samples will be processed using liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR). The LC-MS analyses will be carried out on a Sciex triple quadrupole mass spectrometer couple to an Exion ultra-performance LC system. The targeted analysis will utilize the Biocrates Q500 targeted metabolomics assay which quantifies more than 500 metabolites over 26 chemical classes (Biocrates Inc., Innsbruck, Austria). Data processing to yield metabolite concentrations in micromolar units will utilize the Biocrates MetIDQ software. The NMR data will be acquired on a Bruker Avance NEO 700 MHz NMR equipped with a TCI cryoprobe and a SampleXPress automatic sample changer. The data will be processed using the Chenomx NMR Processor and Profiler packages (Chenomx, Edmonton, CA) to yield quantitative data in millimolar units.
Time frame: 1, 5, 9, and optional at 24 months
Problem Areas in Diabetes (PAID-Ped) - child
Validated questionnaire, scored according to published standards. Scores range 0-100, higher scores indicate greater burden.
Time frame: 1, 5, 9, and optional at 24 months
Problem Areas in Diabetes (PAID-PR) - parent
Validated questionnaire, scored according to published standards. Scores range 0-100, higher scores indicate greater burden.
Time frame: 1, 5, 9, and optional at 24 months
Pediatric Quality of Life (PEDSQL) General Module - parent
Validated questionnaire, scored according to published standards. Scores range 0-100, higher scores indicate better quality of life.
Time frame: 1, 5, 9, and optional at 24 months
Pediatric Quality of Life (PEDSQL) General Module - child
Validated questionnaire, scored according to published standards. Scores range 0-100, higher scores indicate better quality of life.
Time frame: 1, 5, 9, and optional at 24 months
Pediatric Quality of Life (PEDSQL) Diabetes Module - parent
Validated questionnaire, scored according to published standards. Scores range 0-100, higher scores indicate less problems.
Time frame: 1, 5, 9, and optional at 24 months
Pediatric Quality of Life (PEDSQL) Diabetes Module - child
Validated questionnaire, scored according to published standards. Scores range 0-100, higher scores indicate less problems.
Time frame: 1, 5, 9, and optional at 24 months
Child Eating Disorder Examination Questionnaire (ChEDE-Q8)
Validated questionnaire, scored according to published standards. Scores range 0-42, higher scores are worse.
Time frame: 1, 5, 9, and optional at 24 months
Perceptions on Diet Management of Diabetes
Questionnaire to assess participants' and caregivers' perceptions of the influence of the diet on their diabetes management.
Time frame: 1, 5, 9, and optional at 24 months
Qualitative patient perspectives, interview - parent
Interviews will be held with children and caregivers separately after implementation and completion of the intervention.
Time frame: optional at 9 months
Qualitative patient perspectives, interview - child
Interviews will be held with children and caregivers separately after implementation and completion of the intervention.
Time frame: optional at 9 months
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