Effects of Ketosis on Brain Function in Patients With T1DM
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04219709|
Recruitment Status : Recruiting
First Posted : January 7, 2020
Last Update Posted : January 7, 2020
|Condition or disease||Intervention/treatment||Phase|
|Type1diabetes||Other: Very low carbohydrate diet Other: Standard carbohydrate diet||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Participants will be randomized in a parallel design to receive a standard carbohydrate diet versus very low carbohydrate diet. Both of diet groups will undergo euglycemic-hypoglycemic insulin clamps and MRI studies to assess brain hypoglycemia tolerance. The standard diet group will undergo an additional euglycemic-hypoglycemic insulin clamp - with and without exogenous oral ketones in random order.|
|Masking:||None (Open Label)|
|Primary Purpose:||Supportive Care|
|Official Title:||Brain Function, Cognition, and Hypoglycemia Tolerance in Patients With Type 1 Diabetes Mellitus in the Setting of Nutritional Ketosis Versus Standard Carbohydrate Diet|
|Actual Study Start Date :||January 3, 2020|
|Estimated Primary Completion Date :||December 31, 2020|
|Estimated Study Completion Date :||June 30, 2021|
Experimental: Very low carbohydrate diet
Dietary Intervention, food delivery
Other: Very low 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.
Active Comparator: Standard 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 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 [ Time Frame: Diet week 5-12 ]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
- Resting brain activation changes in brain areas related to cognition during hypoglycemia [ Time Frame: Diet week 5-12 ]Resting brain activation will be measured by arterial spin labeling (ASL) during euglycemia and hypoglycemia and differences will be reported
- Task-related brain activation changes during hypoglycemia in brain areas related to cognition [ Time Frame: Diet week 5-12 ]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
- Functional connectivity changes in brain areas related to cognition during hypoglycemia [ Time Frame: Diet week 5-12 ]Functional connectivity activation will be measured using resting state functional MRI during euglycemia and hypoglycemia and differences will be reported
- Response time changes during hypoglycemia [ Time Frame: Diet week 5-12 ]Response time to a working-memory cognitive task (n-back) will be measured during hypoglycemia and compared to the response time in euglycemia
- Cognitive performance during hypoglycemia [ Time Frame: Diet week 5-12 ]Response accuracy of a cognitive task (n-back) during hypoglycemia compared to euglycemia will be reported
- Hypoglycemia symptoms [ Time Frame: Diet week 5-12 ]A Hypoglycemia Symptoms Scale comprising 4 autonomic/neurogenic (sweating, palpitations, shaking, hunger) and 5 neuroglycopenic (drowsiness, confusion, difficulty concentrating, lightheadedness, and blurry vision) symptoms will be used to assess each symptom on a 0-10 visual analog scale (VAS) during euglycemia, hypoglycemia, and at the timepoint of participant report of hypoglycemic symptoms during the glycemic descent phase. Average scores for hypoglycemia symptoms overall, autonomic/neurogenic symptoms, and neuroglycopenic symptoms will be reported for each timepoint.
- Threshold for counter-regulatory hormone response [ Time Frame: Diet week 5-12 ]Levels of counter-regulatory hormone (epinephrine, glucagon, growth hormone, cortisol) will be measured every 10-15 minutes during the glycemic descent and hypoglycemic period and the blood glucose level at which a rise is first detected will be reported
- Levels of counter-regulatory hormones [ Time Frame: Diet week 5-12 ]Levels of counter-regulatory hormones (epinephrine, glucagon, growth hormone, cortisol) will be measured during at baseline, at the start and end of the euglycemic phase, and then every 10-15 minutes during glycemic descent and hypoglycemic period. Averages will be reported at each time point.
- Blood glucose level at which participant reports symptoms of hypoglycemia. [ Time Frame: Diet week 5-12 ]Participants will be instructed to push a response button when they first notice any symptoms of hypoglycemia during the glycemic descent phase.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04219709
|Contact: Svetlana Azova, MDemail@example.com|
|Contact: Belinda Lennerz, MD, PhDfirstname.lastname@example.org|
|United States, Massachusetts|
|Boston Children's Hospital||Recruiting|
|Boston, Massachusetts, United States, 02115|
|Contact: Svetlana C Azova, MD 617-919-6675 ext 6179196675 email@example.com|
|Contact: Belinda S Lennerz, MD PhD 8572183896 firstname.lastname@example.org|
|Principal Investigator:||Belinda Lennerz, MD, PhD||Boston Children’s Hospital|