An interventional study of Very low carbohydrate diet and Standard carbohydrate diet in Type1diabetes, sponsored by Boston Children's Hospital. Recruiting at 1 site in United States. Open to participants aged 18 Years to 40 Years. Per ClinicalTrials.gov, last updated 2024-12-18.
Sponsored by Boston Children's Hospital · Not applicable, Interventional, and Supportive care
The scientific goal of this study is to examine the effects of a ketogenic diet on hypoglycemia tolerance and brain function in people with type 1 diabetes mellitus (T1D) and to clarify the mechanistic role of ketones in this process. Glycemic management of T1D is typified by alternating periods of hyper- and hypo-glycemia. Because brain metabolism under usual conditions depends on glucose, acute hypoglycemia leads to immediate complications including impaired cognitive function and a counter-regulatory hormone response. Recurrent hypoglycemia is associated with functional and structural changes in the brain and contributes to the cognitive decline observed in individuals with diabetes. The state of nutritional ketosis (as it occurs during fasting or when following a ketogenic [very low carbohydrate] diet) may protect against these acute and chronic complications. As the body relies on fat metabolism, ketone bodies build up and provide an alternative fuel for the brain. Studies during hypoglycemia have shown better cognitive function and less hypoglycemia symptoms in the setting of nutritional ketosis or with ketone administration. This physiological benefit may have special relevance for people with T1D who experience hypoglycemia frequently. To date, no mechanistic studies have examined brain effects of nutritional ketosis in T1D; nor have any trials explored the potential relevance of this for diabetes care.
To test the hypothesis that a ketogenic diet increases hypoglycemia tolerance and improves brain function and cognitive performance during hypoglycemia, the researchers propose a randomized mechanistic study using insulin infusions and neuroimaging. The study will leverage an existing randomized controlled trial (RCT) in 32 young adults with T1D who will receive a ketogenic vs a standard carbohydrate diet for 12 weeks. Researchers will conduct a euglycemic-hypoglycemic insulin clamp using a continuous infusion of insulin, along with a glucose infusion that is adjusted to keep blood glucose levels normal (90 mg/dL), followed by a slow drop to hypoglycemia (50 mg/dL). Researchers will assess activation and connectivity of relevant brain areas by magnetic resonance imaging (MRI). Using continuous imaging during the gradual glycemic descent from 90 mg/dL to 50 mg/dL, the researchers will establish the glycemic threshold at which the hypothalamus becomes activated. Using a combination of MRI modalities, they will assess brain activation and connectivity changes during hypoglycemia versus euglycemia, both during rest and in relation to a cognitive task. Brain findings will be integrated with physiologic (blood levels of glucose, ketones, free fatty acids, counter-regulatory hormones) and behavioral (reaction time, cognitive task performance, hypoglycemia symptoms scale) parameters. In additional studies, researchers will give an oral ketone drink to raise blood ketone levels in participants in the standard carbohydrate diet arm. They will perform the same insulin infusion and MRI investigations to clarify the mechanistic role of ketones in mediating brain activation patterns. Comparison will be between nutritional vs no ketosis, exogenous vs no ketosis, and nutritional vs exogenous ketosis.
218 studies on the registry are indexed under Ketosis; 50 are open to participants now.
This study's planned enrollment of 24 is above the median of 20 across 190 interventional studies indexed under Ketosis.
Browse Ketosis studies →Boston Children's Hospital is the lead sponsor of 608 studies on the registry; 147 are open to participants now.
Of its 32 completed or terminated interventional studies of FDA-regulated products, 19 (59%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
For participants who undergo MRI:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Dietary Intervention, food delivery
Other: Very low carbohydrate diet
Dietary Intervention, food delivery
Other: Standard carbohydrate diet
All meals will be delivered and participants will consume study foods exclusively. Participants will receive a fiber supplement with each meal as needed to promote digestive health, and a daily multi-vitamin, magnesium and omega-3 supplement to ascertain micronutrient sufficiency. Participants will be weighed at each study visit and the diet plan will be adjusted for satiety and weight-maintenance. The diet composition will be as follows: 5% carbohydrate, 75% fat, 20% protein.
All meals will be delivered and participants will consume study foods exclusively. Participants will receive a daily multi-vitamin and omega-3 supplement to ascertain micronutrient sufficiency. Participants will be weighed at each study visit and the diet plan will be adjusted for satiety and weight-maintenance. The diet composition will be as follows: 50% carbohydrate, 30% fat, 20% protein.
Glycemic threshold for hypothalamic activation
The blood glucose level at which hypothalamic activation is detected by continuous BOLD functional MRI during a 40 min glycemic descent from 90 to 50 mg/dL
Time frame: Diet week 5-12
Resting brain activation changes in brain areas related to cognition during hypoglycemia
Resting brain activation will be measured by arterial spin labeling (ASL) during euglycemia and hypoglycemia and differences will be reported
Time frame: Diet week 5-12
Task-related brain activation changes during hypoglycemia in brain areas related to cognition
Task-related brain activation will be measured during a working memory task (n-back) by BOLD during euglycemia and hypoglycemia and differences will be reported
Time frame: Diet week 5-12
Functional connectivity changes in brain areas related to cognition during hypoglycemia
Functional connectivity activation will be measured using resting state functional MRI during euglycemia and hypoglycemia and differences will be reported
Time frame: Diet week 5-12
Response time changes during hypoglycemia
Response time to a working-memory cognitive task (n-back) will be measured during hypoglycemia and compared to the response time in euglycemia
Time frame: Diet week 5-12
Cognitive performance during hypoglycemia
Response accuracy of a cognitive task (n-back) during hypoglycemia compared to euglycemia will be reported
Time frame: Diet week 5-12
Hypoglycemia symptoms
A Hypoglycemia Symptoms Scale comprising 6 autonomic/neurogenic (sweating, palpitations, trembling, weakness, nausea, and hunger) and 5 neuroglycopenic (drowsiness, confusion, difficulty concentrating, lightheadedness, and headache) symptoms will be used to assess each symptom on a 0-4 scale (higher scores indicate more symptoms) during euglycemia and hypoglycemia. Average scores for hypoglycemia symptoms overall, autonomic/neurogenic symptoms, and neuroglycopenic symptoms will be reported for each time point.
Time frame: Diet week 5-12
Blood glucose level at which participant reports symptoms of hypoglycemia.
Participants will be instructed to push a response button when they first notice any symptoms of hypoglycemia during the glycemic descent phase.
Time frame: Diet week 5-12
Plan to share: No
No publications or documents are linked to this record.
Started Jan 2020 (actual). Primary completion is estimated for Jul 2026, 78 months after the start.
Of 99 non-industry interventional studies with no phase under Ketosis, half reached primary completion within 14 months of starting (the median), counting those still running; a quarter within 7 and three quarters within 24. This study's planned 78 months is above that.
Counting every sponsor, half of 103 studies reached it within 14 months; a quarter within 7 and three quarters within 24.
How these figures are worked out, and which studies are left out of them.
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