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Dynamic Connectivity Under Metabolic Constraints

25 septembre 2019 mis à jour par: 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.

Aperçu de l'étude

Statut

Inconnue

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Anticipé)

80

Phase

  • Phase 4

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • États-Unis
    • Massachusetts
      • Charlestown, Massachusetts, États-Unis, 02129
        • Recrutement
        • Martinos Center for Biomedical Research, Building 149
    • New York
      • Stony Brook, New York, États-Unis, 11794
        • Recrutement
        • Bioengineering Building , Stony Brook University
        • Chercheur principal:
          • Lilianne Mujica-Parodi, PhD

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 79 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Science basique
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation croisée
  • Masquage: Seul

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 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).
Médicament: Glucose
Supplement administered mid-scan.
Expérimental: 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).
Médicament: Glucose
Supplement administered mid-scan.
Médicament: Ketones
Supplement administered mid-scan.
Expérimental: 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.
Médicament: Glucose
Supplement administered mid-scan.
Médicament: Ketones
Supplement administered mid-scan.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Diet related changes in brain network stability will be assessed by fMRI BOLD measurements.
Délai: 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
Délai: 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
Délai: 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

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Cognitive performance will be assessed by Mini Mental State Exam (MMSE).
Délai: 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.
Délai: 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.
Délai: 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.
Délai: 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.
Délai: 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

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Stony Brook University

Collaborateurs

Martinos Center for Biomedical Imaging

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

19 juin 2015

Achèvement primaire (Anticipé)

1 septembre 2022

Achèvement de l'étude (Anticipé)

1 septembre 2022

Dates d'inscription aux études

Première soumission

17 septembre 2019

Première soumission répondant aux critères de contrôle qualité

25 septembre 2019

Première publication (Réel)

27 septembre 2019

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

27 septembre 2019

Dernière mise à jour soumise répondant aux critères de contrôle qualité

25 septembre 2019

Dernière vérification

1 septembre 2019

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • 2017D001434

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Oui

Étudie un produit d'appareil réglementé par la FDA américaine

Non

produit fabriqué et exporté des États-Unis.

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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