HypoglycemiaHypo fMRINCT03867344
The Functional Neuroanatomy of the Human Physiological Stress Response
A study testing Hypoglycemic Hyperinsulinemic Clamp and Normoglycemic Hyperinsulinemic Clamp in people with Hypoglycemia and Physiological Stress, run by Brigham and Women's Hospital at 2 sites in United States.
Trial summary
The purpose of this study is to examine the effect of a moderately low blood sugar stress on the nervous system. The investigators hope that information obtained from completing this study will help to reveal information about how a non-psychological stress impacts the parts of the brain that react to stress and the… Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypoglycemia, Physiological Stress
- What is being tested?
- Hypoglycemic Hyperinsulinemic Clamp and Normoglycemic Hyperinsulinemic Clamp
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 74 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Oct 2019to 30 Dec 2025
- Phase
- Interventional
- 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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy volunteers
- Males and Females age 18 to 45 years
- BMI 18-35 kg/m2
Who cannot join
- Pregnancy
- Lactation
- Menopause
- Any medical condition
- Current or prior alcohol or drug abuse
- Active tobacco use
Show all 18Show fewer
- Abnormal ECG
- In all subjects, any individuals on oral, injected, inhaled or topical corticosteroids within the last year or oral contraceptives within the past 3 months will be excluded.
- Use of medications other than thyroid hormone or hormonal birth control
- Serum potassium >5.0 mmol/L
- Estimated GFR <60 mL/min/1.73 m2
- Hemoglobin A1c ≥6.5%
- Patient Health Questionnaire (PHQ9) for depression score ≥15
- GAD-7 Questionnaire for anxiety score ≥10
- PTSD Checklist for DSM-5 (PCL-5) score ≥31
- Perceived Stress Scale (PSS-14) score >28
- Blood pressure systolic ≥140 or <100 mmHg; Blood pressure diastolic >90 mmHg
- Metal in the body including: cardiac pacemakers, stents, artificial heart valves, artificial limbs or hands, brain stimulator devices, implanted drug pumps, ear implants, eye implants or known metal fragments in eyes, exposure to shrapnel or metal filings (wounded in military combat, sheet metal workers, welders, and others), other metallic surgical hardware in vital areas, certain tattoos with metallic ink, certain transdermal medication patches, and metal-containing IUDs
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02115
Brigham and Women's Hospital
Boston, Massachusetts, 02115
About this study
The purpose of this study is to examine the effect of a moderately low blood sugar stress on the nervous system. The investigators hope that information obtained from completing this study will help to reveal information about how a non-psychological stress impacts the parts of the brain that react to stress and the autonomic nervous system. The autonomic nervous system is the part of the nervous system that provides the body with involuntary or automatic control of heart rate, blood pressure, and breathing.
Read the detailed description
Stress is common in daily life and is associated with adverse health outcomes. This proposal will study how a physiological stress (low blood sugar), a stress often experienced by people with diabetes, affects connections in the brain. The investigators will focus on brain connections that are involved in autonomic control of cardiovascular function, and determine both how these brain connections are altered by low blood sugar and how these alterations associate with changes in pain perception and cardiovascular control.
In this study, the investigators introduce a novel mechanistic, integrative approach to the assessment of the response to and recovery from a specific physiologic stressor - insulin-induced hypoglycemia. The overall hypothesis is that a hypoglycemic stress will alter autonomic brain networks, and will affect clinically relevant physiological outcomes (cardiovascular autonomic function); and that the rate and extent of recovery of these brain networks will provide a measure of resilience.
In combination, this approach will allow the investigators for the first time to define the magnitude of the effect of stress exposure on neural circuitry and on clinically relevant stress-related physiological outcomes (cardiovascular autonomic function) and to define the recovery of brain circuitry and these related physiological outcomes.
- Conditions
- Hypoglycemia, Physiological Stress
- Being tested
- Hypoglycemic Hyperinsulinemic Clamp, Normoglycemic Hyperinsulinemic Clamp
- Keywords
- Hypoglycemia, Stress, Brain
- Medical subject headings
- Hypoglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hypoglycemic Hyperinsulinemic ClampOther
Also called Hypoglycemic Hyperinsulinemic Clamp Procedure
Participants undergo a 120-minute hypoglycemic hyperinsulinemic clamp procedure.
Normoglycemic Hyperinsulinemic ClampOther
Also called Normoglycemic Hyperinsulinemic Clamp Procedure
Participants undergo a 120-minute normoglycemic hyperinsulinemic clamp procedure.
| Study group | Role | What they receive |
|---|---|---|
| Hypoglycemia | Active comparator | Participants undergo Autonomic Nervous System (ANS) Testing (measurement of Baroreflex Sensitivity using the Modified Oxford test) followed by a functional MRI (fMRI) scan. The next day, participants undergo one 120-minute hypoglycemic hyperinsulinemic clamp procedure (50mg/dL) in the morning followed by ANS Testing and an fMRI scan. Four days later, participants undergo repeat ANS Testing and an fMRI scan. Receives: Other: Hypoglycemic Hyperinsulinemic Clamp |
| Normoglycemia | Placebo comparator | Participants undergo Autonomic Nervous System (ANS) Testing (measurement of Baroreflex Sensitivity using the Modified Oxford test) followed by a functional MRI (fMRI) scan. The next day, participants undergo one 120-minute normoglycemic hyperinsulinemic clamp procedure (90mg/dL) in the morning followed by ANS Testing and an fMRI scan. Four days later, participants undergo repeat ANS Testing and an fMRI scan. Receives: Other: Normoglycemic Hyperinsulinemic Clamp |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effect of physiological stress (hypoglycemia) on brain networks involved in autonomic function
Functional MRI will be performed following physiological stress (hypoglycemia) or placebo (normoglycemia) and a functional connectivity analysis will be performed on the fMRI data. The outcome will be alterations in neural network connectivity, as measured by changes in Pearson-correlation coefficients among the following brain structures: right anterior insula and anterior cingulate cortex; right anterior insula and hypothalamus; hypothalamus and anterior cingulate cortex; hypothalamus and amygdala; locus coeruleus and hypothalamus.
Measured: Baseline, 8 hours after physiological stress, and 4 days after physiological stress
The relationship over time between stress-induced changes in brain networks and stress-induced changes in baroreflex sensitivity
The stress-induced change in baroreflex sensitivity (msec/mmHg) will be determined. Pearson correlation coefficients (r) between the changes in baroreflex sensitivity and the changes in brain connectivity (right anterior insula and anterior cingulate cortex; hypothalamus and amygdala [determined for the first outcome above]) will be calculated and tested for significance.
Measured: Baseline, 8 hours after physiological stress, and 4 days after physiological stress
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2019
- Study start1 Oct 2019
- Primary completion30 Dec 2025
- Study completion30 Dec 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypoglycemiaStudies of the same condition, open and under way.
- More trials run by Brigham and Women's 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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Beth Israel Deaconess Medical Center, Boston Children's Hospital, Mclean Hospital
- Responsible party
- Principal investigator, Gail Kurr Adler, Brigham and Women's Hospital
- Investigators
- Roy Freeman, MD, Principal investigator, Beth Israel Deaconess Medical CenterGail K Adler, MD, PhD, Principal investigator, Brigham and Women's HospitalDavid Borsook, MD, PhD, Principal investigator, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03867344
- Sponsor's protocol ID
- 2019P000318
- Acronym
- Hypo fMRI
- Status last verified
- Dec 2025
- First submitted
- 4 Mar 2019
- Last updated
- 5 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The data collected will comply with the NIH requirements for timely release and data sharing. Data will be shared in the form of publications and presentations in scientific forums. As the NIH has noted, the investigators reserve the right to keep the data restricted in order to perform the initial analyses for this grant proposal and will continue to use the data for further, but not prolonged, exclusive use. Of note, the sharing of this data will be limited by at least the following issues, some unique to this proposal and some not unique. Some of the data obtained in this study is defined to be sensitive in nature, which may restrict its ability to be shared. Data may only be shared with the approval of our IRB and is limited by HIPPA and any other regulations that may be promulgated during the course of this proposal.
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Functional Neuroanatomy of the Human Physiological Stress Response
- ClinicalTrials.gov ID
- NCT03867344
- Acronym / sponsor ID
- Hypo fMRI / 2019P000318
- Conditions
- Hypoglycemia, Physiological Stress
- Keywords
- Hypoglycemia, Stress, Brain
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- Beth Israel Deaconess Medical Center, Boston Children's Hospital, Mclean Hospital
- Study start
- 1 Oct 2019 (actual)
- Primary completion
- 30 Dec 2025 (actual)
- Study completion
- 30 Dec 2025 (actual)
- First posted
- 8 Mar 2019 (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.
The purpose of this study is to examine the effect of a moderately low blood sugar stress on the nervous system. The investigators hope that information obtained from completing this study will help to reveal information about how a non-psychological stress impacts the parts of the brain that react to stress and the autonomic nervous system. The autonomic nervous system is the part of the nervous system that provides the body with involuntary or automatic control of heart rate, blood pressure, and breathing.
Detailed description
Stress is common in daily life and is associated with adverse health outcomes. This proposal will study how a physiological stress (low blood sugar), a stress often experienced by people with diabetes, affects connections in the brain. The investigators will focus on brain connections that are involved in autonomic control of cardiovascular function, and determine both how these brain connections are altered by low blood sugar and how these alterations associate with changes in pain perception and cardiovascular control.
In this study, the investigators introduce a novel mechanistic, integrative approach to the assessment of the response to and recovery from a specific physiologic stressor - insulin-induced hypoglycemia. The overall hypothesis is that a hypoglycemic stress will alter autonomic brain networks, and will affect clinically relevant physiological outcomes (cardiovascular autonomic function); and that the rate and extent of recovery of these brain networks will provide a measure of resilience.
In combination, this approach will allow the investigators for the first time to define the magnitude of the effect of stress exposure on neural circuitry and on clinically relevant stress-related physiological outcomes (cardiovascular autonomic function) and to define the recovery of brain circuitry and these related physiological outcomes.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hypoglycemia | Active comparator | Other: Hypoglycemic Hyperinsulinemic ClampParticipants undergo Autonomic Nervous System (ANS) Testing (measurement of Baroreflex Sensitivity using the Modified Oxford test) followed by a functional MRI (fMRI) scan. The next day, participants undergo one 120-minute hypoglycemic hyperinsulinemic clamp procedure (50mg/dL) in the morning followed by ANS Testing and an fMRI scan. Four days later, participants undergo repeat ANS Testing and an fMRI scan. |
| Normoglycemia | Placebo comparator | Other: Normoglycemic Hyperinsulinemic ClampParticipants undergo Autonomic Nervous System (ANS) Testing (measurement of Baroreflex Sensitivity using the Modified Oxford test) followed by a functional MRI (fMRI) scan. The next day, participants undergo one 120-minute normoglycemic hyperinsulinemic clamp procedure (90mg/dL) in the morning followed by ANS Testing and an fMRI scan. Four days later, participants undergo repeat ANS Testing and an fMRI scan. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Healthy volunteers
- Males and Females age 18 to 45 years
- BMI 18-35 kg/m2
Key exclusion criteria (18 listed)
- Pregnancy
- Lactation
- Menopause
- Any medical condition
- Current or prior alcohol or drug abuse
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 |
|---|---|---|
| Hypoglycemic Hyperinsulinemic ClampAlso: Hypoglycemic Hyperinsulinemic Clamp ProcedureParticipants undergo a 120-minute hypoglycemic hyperinsulinemic clamp procedure. | Other | Hypoglycemia |
| Normoglycemic Hyperinsulinemic ClampAlso: Normoglycemic Hyperinsulinemic Clamp ProcedureParticipants undergo a 120-minute normoglycemic hyperinsulinemic clamp procedure. | Other | Normoglycemia |
Primary outcome
Effect of physiological stress (hypoglycemia) on brain networks involved in autonomic function
Time frame: Baseline, 8 hours after physiological stress, and 4 days after physiological stress
Functional MRI will be performed following physiological stress (hypoglycemia) or placebo (normoglycemia) and a functional connectivity analysis will be performed on the fMRI data. The outcome will be alterations in neural network connectivity, as measured by changes in Pearson-correlation coefficients among the following brain structures: right anterior insula and anterior cingulate cortex; right anterior insula and hypothalamus; hypothalamus and anterior cingulate cortex; hypothalamus and amygdala; locus coeruleus and hypothalamus.
The relationship over time between stress-induced changes in brain networks and stress-induced changes in baroreflex sensitivity
Time frame: Baseline, 8 hours after physiological stress, and 4 days after physiological stress
The stress-induced change in baroreflex sensitivity (msec/mmHg) will be determined. Pearson correlation coefficients (r) between the changes in baroreflex sensitivity and the changes in brain connectivity (right anterior insula and anterior cingulate cortex; hypothalamus and amygdala [determined for the first outcome above]) will be calculated and tested for significance.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2026.
- Individual participant dataSharing planned: Yes. The data collected will comply with the NIH requirements for timely release and data sharing. Data will be shared in the form of publications and presentations in scientific forums. As the NIH has noted, the investigators reserve the right to keep the data restricted in order to perform the initial analyses for this grant proposal and will continue to use the data for further, but not prolonged, exclusive use. Of note, the sharing of this data will be limited by at least the following issues, some unique to this proposal and some not unique. Some of the data obtained in this study is defined to be sensitive in nature, which may restrict its ability to be shared. Data may only be shared with the approval of our IRB and is limited by HIPPA and any other regulations that may be promulgated during the course of this proposal.
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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.
Roy Freeman, MD principal investigator
Beth Israel Deaconess Medical Center
Gail K Adler, MD, PhD principal investigator
Brigham and Women's Hospital
David Borsook, MD, PhD principal investigator
Boston Children's Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Hypoglycemic Hyperinsulinemic Clamp and Normoglycemic Hyperinsulinemic Clamp in people with Hypoglycemia and Physiological Stress, run by Brigham and Women's 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 3 inclusion and 18 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: finished, as of the sponsor's last update on 5 Jan 2026. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effect of physiological stress (hypoglycemia) on brain networks involved in autonomic function (time frame: Baseline, 8 hours after physiological stress, and 4 days after physiological stress). The study lists 2 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 5 Jan 2026.