Dynamic Connectivity Under Metabolic Constraints

Healthy Clinical Trial

Official title:

Dynamic Connectivity Under Metabolic Constraints

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04106882
• Other study ID #: 2017D001434
• Status: Recruiting
• Phase: Phase 4
• Start date: June 19, 2015
• Est. completion date: September 2022

Study information

• Verified date: September 2019
• Source: Stony Brook University
• Contact: Lilianne Mujica-Parodi, PhD
• Phone: 631-371-4413
• Email: lilianne.strey[@]stonybrook.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators are studying the impact of insulin resistance on the acceleration of brain aging and testing whether increased neuron insulin resistance can be counteracted by utilization of alternate metabolic pathways (e.g., ketones rather than glucose). This study has three Arms, which together provide synergistic data. For all three Arms, subjects are tested in a within-subjects design that consists of 2-3 testing sessions, 1-14 days apart, and counter-balanced for order. Impact of fuel (glucose in one session, ketones in the other) on brain metabolism and associated functioning is measured during each session. For Arms 1-2, the primary experimental measure is functional magnetic resonance imaging (fMRI), which is used to trace the self-organization of functional networks following changes in energy supply and demand. Arm 1 tests the impact of endogenous ketones produced by switching to a low carbohydrate diet, while Arm 2 tests the impact of exogenous ketones consumed as a nutritional supplement. For Arm 3, simultaneous magnetic resonance spectroscopy/positron-emission tomography (MR/PET) is used to quantify the impact of exogenous ketones on production of glutamate and GABA, key neurotransmitters.

Subjects will be given the option to participate in more than one of the Arms, but doing so is not expected nor required.

Prior to scans, subjects will receive a clinician-administered History and Physical (H&P), which includes vital signs, an oral glucose tolerance test (OGTT), and the comprehensive metabolic blood panel. These will be used to assess diabetes, kidney disease, and electrolytes. If subjects pass screening, they will be provided the option to participate in one or more Arms, which include neuroimaging. To provide a quantitative measure of time-varying metabolic activity throughout the scan, based upon quantitative models of glucose and ketone regulation, as well as to be able to implement safety stopping rules (see below), the investigators will obtain pin-prick blood samples three times: prior to the scan, following consumption of the glucose or ketone drink, and following completion of the scan. To assess effects of increased metabolic demand, the investigators measure brain response to cognitive load, transitioning from resting-state to spatial reasoning through a spatial navigation video task. To assess effects of increased metabolic supply, the investigators measure brain response to glucose or ketone bolus.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: September 2022
• Est. primary completion date: September 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

Exclusion Criteria:

• claustrophobia

• history of neurological disease, heart attack, stroke, kidney disease, or myxedema

• chronic usage of alcohol

• current usage of psychotropic medication

• Type 1 diabetes mellitus

• Regular consumption of insulin, Metformin® or other medications (statins, NSAIDs, beta-blockers, glucocorticoids) that affect glucose and/or insulin utilization.

• difficulty swallowing

• pregnancy

• breastfeeding

• For PET: research imaging-related radiation exposure that exceeds current MGH Radiology Radiation Safety Commitee guidelines.

Inclusion Criteria:

• BMI < 30

• MRI compatible

• For PET with Optional 150 ml Blood Sampling Only: Must weigh at least 110 lbs to minimize risks per PHRC guidelines.

• 20/20 vision or correctable to 20/20 with contact lenses

Related Conditions & MeSH terms

• Aging
• Diet Modification
• Healthy
• Insulin Resistance

Intervention

Drug:
• Ketones
Supplement administered mid-scan.
• Glucose
Supplement administered mid-scan.

Locations

Country	Name	City	State
United States	Martinos Center for Biomedical Research, Building 149	Charlestown	Massachusetts
United States	Bioengineering Building , Stony Brook University	Stony Brook	New York

Sponsors (2)

Lead Sponsor	Collaborator
Stony Brook University	Martinos Center for Biomedical Imaging

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Diet related changes in brain network stability will be assessed by fMRI BOLD measurements.	Changes in BOLD signal measurements will be observed between baseline and during a glycolytic, fasting, or ketotic state.	Within two weeks of enrollment completion
Primary	Glucose uptake will be measured by PET, with and without ketone supplement	Continuous FDG PET infusion is used as a measure of glucose uptake during rest and task, with and without the ketone supplement.	Within two weeks of enrollment completion
Primary	Neurotransmitter production with and without ketone supplement will be measured by magnetic resonance spectroscopy	Changes in neurotransmitter concentration under metabolic demands (i.e., task vs resting-state) with and without ketone supplement will be assessed by magnetic resonance spectroscopy.	Within two weeks of enrollment completion
Secondary	Cognitive performance will be assessed by Mini Mental State Exam (MMSE).	All subjects will undergo cognitive testing prior to MRI scanning using the MMSE exam.	Within two weeks of enrollment completion
Secondary	Cognitive performance will be assessed by CNS Vital Signs.	All subjects will undergo cognitive testing prior to MRI scanning using the CNS Vital Signs exam.	Within two weeks of enrollment completion
Secondary	Insulin resistance will be assessed by HbA1C.	All subjects will be tested for insulin resistance prior to MRI scanning using veinous blood collected and tested for HbA1C.	Within two weeks of enrollment completion
Secondary	Insulin resistance will be assessed by blood insulin level.	All subjects will be tested for insulin resistance prior to MRI scanning using veinous blood collected and tested for insulin during a 2-hour Oral Glucose Tolerance Test (OGTT).	Within two weeks of enrollment completion
Secondary	Insulin resistance will be assessed by blood glucose level.	All subjects will be tested for insulin resistance prior to MRI scanning using veinous blood collected and tested for glucose during a 2-hour Oral Glucose Tolerance Test (OGTT).	Within two weeks of enrollment completion