Insulin ResistancePhase 4NCT04840095
Dynamic Connectivity Under Metabolic Constraints
A Phase 4 study testing Ketones and Glucose in people with Insulin Resistance and Healthy, run by Massachusetts General Hospital at 2 sites in United States.
Trial summary
In this study, we investigate the impact of insulin resistance on the acceleration of brain aging, and test 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 2023
- 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
- 20/20 vision or correctable to 20/20 with contact lenses
- MRI compatible
- For PET with Optional 150 ml Blood Sampling Only: Must weigh at least 110 lbs to minimize risks per PHRC guidelines.
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.
Antoine Hone-Blanchet, PhD contact
United States2 sites, 1 recruiting
- Recruiting
Martinos Center for Biomedical Research, Building 149
Charlestown, Massachusetts, 02129
Botond Antal, MS, botond.antal@stonybrook.edu
- Active, not recruiting
Bioengineering Building , Stony Brook University
Stony Brook, New York, 11794
About this study
In this study, we investigate the impact of insulin resistance on the acceleration of brain aging, and test 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. During each session we measure the impact of fuel (glucose in one session, ketones in the other) on brain metabolism and associated functioning. For Arms 1-2, our primary experimental measure is functional magnetic resonance imaging (fMRI), which we will use 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, we use simultaneous magnetic resonance spectroscopy/positron-emission tomography (MR/PET) 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), we 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, we measure brain response to cognitive load, transitioning from resting-state to spatial reasoning through a Tetris task. To assess effects of increased metabolic supply, we measure brain response to glucose or ketone bolus.
- Conditions
- Insulin Resistance, Healthy, Diet Modification, Aging
- Being tested
- Ketones, Glucose
- Keywords
- exogenous ketone, insulin resistance, 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
Sports supplement that is administered mid-scan.
GlucoseDrug
Supplement is administered mid-scan.
| Study group | Role | What they receive |
|---|---|---|
| Metabolic Manipulation via Diet fMRI | Experimental | 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. Our data analyses quantify network reorganization in response to changing energy constraints (i.e., cognitive demand, fuel). Receives: Drug: Glucose |
| Metabolic Manipulation via Ketone Supplement fMRI | Experimental | 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. Our data analyses quantify network reorganization in response to changing energy constraints (i.e., cognitive demand, fuel). Receives: Drug: Ketones; Drug: Glucose |
| Metabolic Manipulation via Ketone Supplement MR/PET | Experimental | All subjects are tested twice, both times in a fasting condition (8 hours no food, unrestricted water). For both sessions, we will intravenously administer the FDG radioisotope continuously throughout the scan. Thus, PET will map glucose uptake across the brain, while we simultaneously use MRS 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.
fMRI stability measures: endogenous ketones vs exogenous glucose
BOLD signal measurements will be obtained at baseline and during either a glycolytic, fasting, or ketotic state. We hypothesize that ketones provide the brain with greater baseline access to energy, particularly as individuals age and become insulin resistant, and that subsequent ingestion of glucose disrupts this access. We also expect that these effects will become more pronounced when metabolic demands are higher (i.e., task vs resting-state).
Measured: Within two weeks of enrollment completion
fMRI stability measures: exogenous ketones vs exogenous glucose
BOLD signal measurements will be obtained at baseline and following either a glucose or ketone supplement. We hypothesize that ketones provide the brain with greater baseline access to energy, particularly as individuals age and become insulin resistant, and that subsequent ingestion of glucose disrupts this access. We also expect that these effects will become more pronounced when metabolic demands are higher (i.e., task vs resting-state).
Measured: Within two weeks of enrollment completion
PET: glucose uptake and neurotransmitter production with and without ketone supplement
During MR/PET scans, continuous FDG infusion will be used to measure glucose uptake both during rest and task. Magnetic resonance spectroscopy will be used to measure production of neurotransmitters. In individuals who are insulin resistant, we expect to find diminished neurotransmitter levels that will then be replenished through exogenous ketones. We also hypothesize that these effects will become more pronounced when metabolic demands are higher (i.e., task vs resting-state).
Measured: Within two weeks of enrollment completion
Secondary outcomes (1)
Cognitive performance will be assessed and correlated with brain stability values and insulin resistance levels
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.
- First posted9 Apr 2021
- Study start19 Jun 2015
- Primary completionSep 2023 (estimated)
- Study completionSep 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Insulin ResistanceStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Martinos Center for Biomedical Imaging
- Responsible party
- Principal investigator, Lilianne R. Strey, Massachusetts General Hospital
- Investigators
- Lilianne Mujica-Parodi, PhD, Principal investigator, Stony Brook University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04840095
- Sponsor's protocol ID
- 2015P000652
- Status last verified
- Jan 2023
- First submitted
- 7 Apr 2021
- Last updated
- 12 Jan 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dynamic Connectivity Under Metabolic Constraints
- ClinicalTrials.gov ID
- NCT04840095
- Acronym / sponsor ID
- 2015P000652
- Conditions
- Insulin Resistance, Healthy, Diet Modification, Aging
- Keywords
- exogenous ketone, insulin resistance, glucose, diet, aging
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Martinos Center for Biomedical Imaging
- Study start
- 19 Jun 2015 (actual)
- Primary completion
- Sep 2023 (estimated)
- Study completion
- Sep 2023 (estimated)
- First posted
- 9 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this study, we investigate the impact of insulin resistance on the acceleration of brain aging, and test 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. During each session we measure the impact of fuel (glucose in one session, ketones in the other) on brain metabolism and associated functioning. For Arms 1-2, our primary experimental measure is functional magnetic resonance imaging (fMRI), which we will use 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, we use simultaneous magnetic resonance spectroscopy/positron-emission tomography (MR/PET) 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), we 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, we measure brain response to cognitive load, transitioning from resting-state to spatial reasoning through a Tetris task. To assess effects of increased metabolic supply, we measure brain response to glucose or ketone bolus.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Metabolic Manipulation via Diet fMRI | Experimental | Drug: GlucoseAll 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. Our data analyses quantify network reorganization in response to changing energy constraints (i.e., cognitive demand, fuel). |
| Metabolic Manipulation via Ketone Supplement fMRI | Experimental | Drug: Ketones, Drug: GlucoseAll 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. Our data analyses quantify network reorganization in response to changing energy constraints (i.e., cognitive demand, fuel). |
| Metabolic Manipulation via Ketone Supplement MR/PET | Experimental | Drug: Ketones, Drug: GlucoseAll subjects are tested twice, both times in a fasting condition (8 hours no food, unrestricted water). For both sessions, we will intravenously administer the FDG radioisotope continuously throughout the scan. Thus, PET will map glucose uptake across the brain, while we simultaneously use MRS 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. |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- BMI < 30
- 20/20 vision or correctable to 20/20 with contact lenses
- MRI compatible
- For PET with Optional 150 ml Blood Sampling Only: Must weigh at least 110 lbs to minimize risks per PHRC guidelines.
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KetonesSports supplement that is administered mid-scan. | Drug | Metabolic Manipulation via Ketone Supplement MR/PET, Metabolic Manipulation via Ketone Supplement fMRI |
| GlucoseSupplement is administered mid-scan. | Drug | Metabolic Manipulation via Diet fMRI, Metabolic Manipulation via Ketone Supplement MR/PET, Metabolic Manipulation via Ketone Supplement fMRI |
Primary outcome
fMRI stability measures: endogenous ketones vs exogenous glucose
Time frame: Within two weeks of enrollment completion
BOLD signal measurements will be obtained at baseline and during either a glycolytic, fasting, or ketotic state. We hypothesize that ketones provide the brain with greater baseline access to energy, particularly as individuals age and become insulin resistant, and that subsequent ingestion of glucose disrupts this access. We also expect that these effects will become more pronounced when metabolic demands are higher (i.e., task vs resting-state).
fMRI stability measures: exogenous ketones vs exogenous glucose
Time frame: Within two weeks of enrollment completion
BOLD signal measurements will be obtained at baseline and following either a glucose or ketone supplement. We hypothesize that ketones provide the brain with greater baseline access to energy, particularly as individuals age and become insulin resistant, and that subsequent ingestion of glucose disrupts this access. We also expect that these effects will become more pronounced when metabolic demands are higher (i.e., task vs resting-state).
PET: glucose uptake and neurotransmitter production with and without ketone supplement
Time frame: Within two weeks of enrollment completion
During MR/PET scans, continuous FDG infusion will be used to measure glucose uptake both during rest and task. Magnetic resonance spectroscopy will be used to measure production of neurotransmitters. In individuals who are insulin resistant, we expect to find diminished neurotransmitter levels that will then be replenished through exogenous ketones. We also hypothesize that these effects will become more pronounced when metabolic demands are higher (i.e., task vs resting-state).
1 secondary outcome
Cognitive performance will be assessed and correlated with brain stability values and insulin resistance levels
Time frame: Within two weeks of enrollment completion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2023.
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Healthy Volunteer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Antoine Hone-Blanchet, PhD contact
Lilianne Mujica-Parodi, PhD principal investigator
Stony Brook University
2 sites in 1 country: see every site and its status.
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 Massachusetts General Hospital 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 12 Jan 2023. 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?
fMRI stability measures: endogenous ketones vs exogenous glucose (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?
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 12 Jan 2023.