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Insulin ResistancePhase 4NCT04106882

Dynamic Connectivity Under Metabolic Constraints

A Phase 4 study testing Ketones and Glucose in people with Insulin Resistance and Healthy, run by Stony Brook University at 2 sites in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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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). Read more about this study

Who is it for?
Ages 18 to 79 yearsHealthy volunteers can take part
Conditions the study is for
Insulin Resistance, Healthy, Diet Modification
What is being tested?
Ketones and Glucose
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
2 sitesUnited States
Study dates
19 Jun 2015to Sep 2022
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 79 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

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

Trial locations and contacts

2 sites in 1 country.

Lilianne Mujica-Parodi, PhD contact

631-371-4413

lilianne.strey@stonybrook.edu

Liam McMahon, BA contact

liam.mcmahon@stonybrook.edu

United States2 sites, 2 recruiting

  • Martinos Center for Biomedical Research, Building 149

    Charlestown, Massachusetts, 02129

    Recruiting

  • Bioengineering Building , Stony Brook University

    Stony Brook, New York, 11794

    Lilianne Mujica-Parodi, PhD

    Recruiting

Other trials in United States

About this study

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.

Being tested
Ketones, Glucose
Keywords
insulin resistance, exogenous ketone, glucose, diet, aging
Medical subject headings
Insulin Resistance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • KetonesDrug

    Supplement administered mid-scan.

  • GlucoseDrug

    Supplement administered mid-scan.

Study groups in NCT04106882
Study groupRoleWhat they receive
Arm 1: Metabolic Manipulation via Diet fMRIExperimentalAll 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).
Receives: Drug: Glucose
Arm 2: Metabolic Manipulation via Ketone Supplement fMRIExperimentalAll 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).
Receives: Drug: Ketones; Drug: Glucose
Arm 3: Metabolic Manipulation via Ketone Supplement MR/PETExperimentalAll 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.
Receives: Drug: Ketones; Drug: Glucose

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Within two weeks of enrollment completion

  2. 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.

    Measured: Within two weeks of enrollment completion

  3. 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.

    Measured: Within two weeks of enrollment completion

Secondary outcomes (5)

  1. 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.

    Measured: Within two weeks of enrollment completion

  2. 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.

    Measured: Within two weeks of enrollment completion

  3. 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.

    Measured: Within two weeks of enrollment completion

  4. 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).

    Measured: Within two weeks of enrollment completion

  5. 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).

    Measured: Within two weeks of enrollment completion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Sep 2019
  2. Study start19 Jun 2015
  3. Primary completionSep 2022 (estimated)
  4. Study completionSep 2022 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Crossover
Masking
Single blind
Who is masked
Participant
Enrolment
80 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04106882
Sponsor's protocol ID
2017D001434
Status last verified
Sep 2019
First submitted
17 Sep 2019
Last updated
27 Sep 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Ketones and Glucose in people with Insulin Resistance and Healthy, run by Stony Brook University at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 27 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Lilianne Mujica-Parodi, PhD (631-371-4413, lilianne.strey@stonybrook.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Diet related changes in brain network stability will be assessed by fMRI BOLD measurements. (time frame: Within two weeks of enrollment completion). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04106882.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2019; AzTrials last refreshed its copy on 2 Nov 2026.

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