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Dynamic Connectivity Under Metabolic Constraints

25 september 2019 bijgewerkt door: Stony Brook University

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.

Studie Overzicht

Toestand

Onbekend

Conditie

Interventie / Behandeling

Studietype

Ingrijpend

Inschrijving (Verwacht)

80

Fase

  • Fase 4

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Verenigde Staten
    • Massachusetts
      • Charlestown, Massachusetts, Verenigde Staten, 02129
        • Werving
        • Martinos Center for Biomedical Research, Building 149
    • New York
      • Stony Brook, New York, Verenigde Staten, 11794
        • Werving
        • Bioengineering Building , Stony Brook University
        • Hoofdonderzoeker:
          • Lilianne Mujica-Parodi, PhD

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar tot 79 jaar (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Fundamentele wetenschap
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Crossover-opdracht
  • Masker: Enkel

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Arm 1: Metabolic Manipulation via Diet fMRI
All subjects are tested three times, each in a different diet-induced metabolic state: glycolytic (glucose burning), fasting (8 hours no food), and ketotic (fat burning). While having their brains scanned with MRI, subjects are initially tested at rest, and then perform a task. Midway through the session, subjects are removed from the scanner and drink up to 75g glucose. Data analyses quantify network reorganization in response to changing energy constraints (i.e., cognitive demand, fuel).
Geneesmiddel: Glucose
Supplement administered mid-scan.
Experimenteel: Arm 2: Metabolic Manipulation via Ketone Supplement fMRI
All subjects are tested twice, both times in a fasting condition (8 hours no food, unrestricted water). While having their brains scanned with MRI, subjects are initially tested at rest, and then perform a task. Midway through the session, subjects are removed from the scanner and drink either of two fuel sources. In the ketotic (ketone burning) session they will drink a ketone sports drink dosed at 395mg/kg. During the glycolytic (glucose burning) session the same subjects will drink a bolus of glucose, calorie-matched to the ketones. Data analyses quantify network reorganization in response to changing energy constraints (i.e., cognitive demand, fuel).
Geneesmiddel: Glucose
Supplement administered mid-scan.
Geneesmiddel: Ketones
Supplement administered mid-scan.
Experimenteel: Arm 3: Metabolic Manipulation via Ketone Supplement MR/PET
All subjects are tested twice, both times in a fasting condition (8 hours no food, unrestricted water). For both sessions, the investigators will intravenously administer the FDG radioisotope continuously throughout the scan. Thus, PET will map glucose uptake across the brain, while MRS is simultaneously used to measure production of the neurotransmitters glutamine and GABA. While having their brains scanned with MR/PET, subjects are initially tested at rest, and then perform a task. Subjects will drink a ketone sports drink dosed at 395mg/kg. During the glycolytic (glucose burning) session the same subjects will drink a bolus of glucose, calorie-matched to the ketones.
Geneesmiddel: Glucose
Supplement administered mid-scan.
Geneesmiddel: Ketones
Supplement administered mid-scan.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Diet related changes in brain network stability will be assessed by fMRI BOLD measurements.
Tijdsspanne: Within two weeks of enrollment completion
Changes in BOLD signal measurements will be observed between baseline and during a glycolytic, fasting, or ketotic state.
Within two weeks of enrollment completion
Glucose uptake will be measured by PET, with and without ketone supplement
Tijdsspanne: Within two weeks of enrollment completion
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
Neurotransmitter production with and without ketone supplement will be measured by magnetic resonance spectroscopy
Tijdsspanne: Within two weeks of enrollment completion
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

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Cognitive performance will be assessed by Mini Mental State Exam (MMSE).
Tijdsspanne: Within two weeks of enrollment completion
All subjects will undergo cognitive testing prior to MRI scanning using the MMSE exam.
Within two weeks of enrollment completion
Cognitive performance will be assessed by CNS Vital Signs.
Tijdsspanne: Within two weeks of enrollment completion
All subjects will undergo cognitive testing prior to MRI scanning using the CNS Vital Signs exam.
Within two weeks of enrollment completion
Insulin resistance will be assessed by HbA1C.
Tijdsspanne: Within two weeks of enrollment completion
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
Insulin resistance will be assessed by blood insulin level.
Tijdsspanne: Within two weeks of enrollment completion
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
Insulin resistance will be assessed by blood glucose level.
Tijdsspanne: Within two weeks of enrollment completion
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

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Stony Brook University

Medewerkers

Martinos Center for Biomedical Imaging

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

19 juni 2015

Primaire voltooiing (Verwacht)

1 september 2022

Studie voltooiing (Verwacht)

1 september 2022

Studieregistratiedata

Eerst ingediend

17 september 2019

Eerst ingediend dat voldeed aan de QC-criteria

25 september 2019

Eerst geplaatst (Werkelijk)

27 september 2019

Updates van studierecords

Laatste update geplaatst (Werkelijk)

27 september 2019

Laatste update ingediend die voldeed aan QC-criteria

25 september 2019

Laatst geverifieerd

1 september 2019

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • 2017D001434

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Ja

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

product vervaardigd in en geëxporteerd uit de V.S.

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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