Diabetes Mellitus, Type 1 Clinical Trial
Official title:
Effect of Dietary Carbohydrate on Diabetes Control and Beta Cell Function in Children With Newly Diagnosed Diabetes
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 five study visits held at at baseline, 1, 5, 9 and 24 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 will 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. Comparison will be made between a ketogenic vs standard diet.
Status | Recruiting |
Enrollment | 52 |
Est. completion date | April 30, 2030 |
Est. primary completion date | April 30, 2029 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 5 Years to 12 Years |
Eligibility | Inclusion Criteria: - Children aged 5 to 12 years. - Within one month of diabetes diagnosis. - Type 1 diabetes confirmed by immediate insulin requirement with autoimmunity markers (=2 positive antibodies [glutamate decarboxylase-65, islet-antigen-2, zinc transporter-8, insulin [prior to first insulin dose]). - 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. |
Country | Name | City | State |
---|---|---|---|
United States | Boston Children's Hospital | Boston | Massachusetts |
Lead Sponsor | Collaborator |
---|---|
Boston Children's Hospital | Indiana University, University of South Florida |
United States,
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. — View 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. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Time in tight Range (TIR) 70-140 mg/dl | From CGM - percent time spent in the specified glycemic target range will be computed throughout study participation in 2-week increments. | Over 9 months and at 21 months | |
Other | Time above tight Range (TIR) >140 mg/dl | From CGM - percent time spent in the specified glycemic target range will be computed throughout study participation in 2-week increments. | Over 9 months and at 24 months | |
Other | BOHB (beta-hydroxybutyrate), fasting blood concentration | Obtained at daily increasing to weekly intervals as effect modifier of beta-cell function. | Over 9 months and at 24 months | |
Other | Growth | Safety Measure - Height standard deviation score will be calculated from serial height measurements obtained during study visits using CDC age and sex specific references. | 1, 5, 9, and 24 months | |
Other | Growth velocity | Safety Measure - Growth velocity will be calculated from serial height measurements obtained during study visits. | 1, 5, 9, and 24 months | |
Other | Weigh-gain | Safety Measure - Weight SDS and gain will be calculated from serial weight measures obtained during study visits with calibrated scale. | 1, 5, 9, 24 months | |
Other | Confirmed Ketoacidosis | Safety Measure - Defined by elevated BOHB, blood pH <7.3 and serum bicarbonate <15. Rates will be computed as total number of events divided by total patient years of follow-up. | Over 9 months | |
Other | Severe Hypoglycemia | Safety Measure - Defined as blood glucose < 55 mg/dl and requiring glucagon or resulting in seizure or coma. Rates will be computed as total number of events divided by total patient years of follow-up. | Over 9 months | |
Other | Diabetes Related Emergency Visits | Safety Measure - Rates will be computed as total number of events divided by total patient years of follow-up. | Over 9 months | |
Other | Diabetes Related Hospitalizations | Safety Measure - Rates will be computed as total number of events divided by total patient years of follow-up. | Over 9 months | |
Other | Study termination for disordered eating | Safety Measure - ChEDE-Q8 diagnostic score with clinical confirmation. Total number of events. | Over 9 months | |
Other | Study termination for growth deceleration | Safety Measure - Undesired weight loss or significant deceleration in longitudinal growth may warrant termination of study participation. Total number of events will be computed. | Over 9 months | |
Other | Study termination for dyslipidemia | Safety Measure - LDL >200 mg/dl will trigger review of additional risk factors and may prompt diet modification to lower intake of saturated fats. If persistent, study participation may be terminated. Total number of events will be computed. | Over 9 months | |
Primary | Decline in Beta-cell Function | Change in C-peptide 2-h area under the curve after a mixed-meal tolerance test (?CP). | Change over 1, 5, and 9 months, corrected for baseline | |
Secondary | 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. | Over 9 months and at 24 months | |
Secondary | Longitudinal Change in Beta-cell Function | C-peptide 2-h area under the curve after a mixed-meal tolerance test. | 1, 5, and 24 months | |
Secondary | Duration of Clinical Diabetes Remission | Calculated based on percent children with insulin dose corrected HbA1c (IDAA1c) <9. | 1, 5, 9, and 24 months | |
Secondary | 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. | Over 9 months and at 24 months | |
Secondary | 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. | Over 9 months and at 24 months | |
Secondary | 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. | Over 9 months and at 24 months | |
Secondary | 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. | Over 9 months and at 24 months | |
Secondary | Average Blood Glucose | From CGM - will be computed throughout study participation in 2-week increments. | Over 9 months and at 24 months | |
Secondary | 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. | Over 9 months and at 24 months | |
Secondary | Mean Amplitude of Glycemic Excursions (MAGE) | From CGM - will be computed using published formula throughout study participation in 2-week increments. | Over 9 months and at 24 months | |
Secondary | Total Daily Insulin Dose | From insulin administration device uploads - will be computed in units per kg throughout study participation in 2-week increments. | Over 9 months and at 24 months | |
Secondary | HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) | Calculated from fasting blood draw [fasting insulin (µU/ml) × fasting plasma glucose (mg/dl)]/405. | 1, 5, 9, and 24 months | |
Secondary | BMI | Weight divided by height squared. | 1, 5, 9, and 24 months | |
Secondary | Lipid panel | Fasting blood - total, LDL and HDL cholesterol, and triglycerides. | 1, 5, 9, and 24 months | |
Secondary | HDL to Triglyceride Ratio | Fasting blood | 1, 5, 9, and 24 months | |
Secondary | Lipoprotein Subfractions | Fasting blood | 1, 5, 9, and 24 months | |
Secondary | Inflammasome, targeted | Interleukins 1ß, 17, 23, 6, 10; high sensitivity c-reactive protein; tumor necrosis factor a, interferon gamma | 1, 5, 9, and 24 months | |
Secondary | 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. | 1, 5, 9, and 24 months | |
Secondary | 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. | 1, 5, 9, and 24 months | |
Secondary | Problem Areas in Diabetes (PAID-Ped) - child | Validated questionnaire, scored according to published standards. Scores range 0-100, higher scores indicate greater burden. | 1, 3, 5, 7, 9, and 24 months | |
Secondary | Problem Areas in Diabetes (PAID-PR) - parent | Validated questionnaire, scored according to published standards. Scores range 0-100, higher scores indicate greater burden. | 1, 3, 5, 7, 9, and 24 months | |
Secondary | 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. | 1, 3, 5, 7, 9, and 24 months | |
Secondary | 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. | 1, 3, 5, 7, 9, and 24 months | |
Secondary | Pediatric Quality of Life (PEDSQL) Diabetes Module - parent | Validated questionnaire, scored according to published standards. Scores range 0-100, higher scores indicate less problems. | 1, 3, 5, 7, 9, and 24 months | |
Secondary | Pediatric Quality of Life (PEDSQL) Diabetes Module - child | Validated questionnaire, scored according to published standards. Scores range 0-100, higher scores indicate less problems. | 1, 3, 5, 7, 9, and 24 months | |
Secondary | Child Eating Disorder Examination Questionnaire (ChEDE-Q8) | Validated questionnaire, scored according to published standards. Scores range 0-42, higher scores are worse. | 1, 3, 5, 7, 9, and 24 months | |
Secondary | Perceptions on Diet Management of Diabetes | Questionnaire to assess participants' and caregivers' perceptions of the influence of the diet on their diabetes management. | 1, 3, 5, 7, 9, and 24 months | |
Secondary | Qualitative patient perspectives, interview - parent | Interviews will be held with children and caregivers separately after implementation and completion of the intervention. | 9 months | |
Secondary | Qualitative patient perspectives, interview - child | Interviews will be held with children and caregivers separately after implementation and completion of the intervention. | 9 months |
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