Effects of Ketosis on Brain Function in Patients With T1DM

NCT04219709 | Recruiting DMC

• 1 other identifier: IRB-P00030039_2
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Type1diabetes

Keywords

nutrition; very low carbohydrate diet; ketogenic diet; nutritional ketosis; cognitive function; brain; metabolism; ketones; ketosis

Outcome Measures

Primary Outcomes (1)

• 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

  Diet week 5-12

Secondary Outcomes (7)

• Resting brain activation changes in brain areas related to cognition during hypoglycemia

  Diet week 5-12

• Task-related brain activation changes during hypoglycemia in brain areas related to cognition

  Diet week 5-12

• Functional connectivity changes in brain areas related to cognition during hypoglycemia

  Diet week 5-12

• Response time changes during hypoglycemia

  Diet week 5-12

• Cognitive performance during hypoglycemia

  Diet week 5-12

Study Arms (2)

Very low carbohydrate diet

EXPERIMENTAL

Dietary Intervention, food delivery

Other: Very low carbohydrate diet

Standard diet

ACTIVE COMPARATOR

Dietary Intervention, food delivery

Other: Standard carbohydrate diet

Interventions

Very low carbohydrate diet OTHER

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.

Very low carbohydrate diet

Standard carbohydrate diet OTHER

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.

Standard diet

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Males and females with T1D for at least 1 year
• Age 18 to 40 years
• Tanner stage ≥ IV
• BMI 18.5-35 kg/m2
• Stable glycemic control (HbA1c 6.5-9%)
• Use of a continuous glucose monitor (CGM)
• Use of an insulin pump
• Attendance of at least 1 diabetes care visit over the past 12 months (including virtual)

You may not qualify if:

• Ketoacidosis or severe hypoglycemia with seizure or coma in the past 6 months
• Dietary restrictions or intolerances that are incompatible with the planned food deliveries, e.g. celiac disease, gastroparesis, certain food allergies
• Following a weight-loss or otherwise restrictive diet
• Vigorous exercise \>2 hours on \>3 days a week
• History of an eating disorder or at risk for eating disorder, assessed by the Eating Disorders Diagnostic Scale (EDDS)
• Major medical illness or use of medications other than insulin and metformin that could interfere with metabolic or glycemic variables
• Significant psychiatric illness
• Smoking, use of recreational drugs, or excessive alcohol consumption
• Pregnancy or breastfeeding
• Anemia
• For participants who undergo MRI:
• Irregular menses
• Use of psychotropic medication other than SSRIs or other mild antidepressant or anxiety medications (unless these medications are safe to be held for several days to allow for the acquisition of MRI data).

Sponsors & Collaborators

• Boston Children's Hospital: lead
• Beth Israel Deaconess Medical Center: collaborator

Study Sites (1)

Boston Childrens Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

MeSH Terms

Conditions

Ketosis

Condition Hierarchy (Ancestors)

Acidosis; Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Belinda Lennerz, MD PhD

CONTACT

+1 617 355 7476; belinda.lennerz@childrens.harvard.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Instructor in Pediatric Endocrinology

Model Details: 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.

Study Record Dates

• First Submitted: January 3, 2020
• First Posted: January 7, 2020
• Study Start: January 3, 2020
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: December 18, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)