Back to results

The Functional Neuroanatomy of the Human Physiological Stress Response (Hypo fMRI)

Primary Purpose

Hypoglycemia, Physiological Stress

Status

Recruiting

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Hypoglycemic Hyperinsulinemic Clamp

Normoglycemic Hyperinsulinemic Clamp

About this trial

This is an interventional basic science trial for Hypoglycemia focused on measuring Hypoglycemia, Stress, Brain

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Healthy volunteers
Males and Females age 18 to 45 years
BMI 18-30 kg/m2

Exclusion Criteria:

Pregnancy
Lactation
Menopause
Any medical condition
Current or prior alcohol or drug abuse
Active tobacco use
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
Serum potassium >5.0 mmol/L
Estimated GFR <60 mL/min/1.73 m2
Hemoglobin A1c ≥6.5%
LDL >130 mg/dL; Triglycerides >150 mg/dL
Patient Health Questionnaire (PHQ9) for depression score ≥15
GAD-73 Questionnaire for anxiety score ≥10
Primary Care PTSD Screen for DSM-5 for post-traumatic stress disorder score ≥10
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

Sites / Locations

Beth Israel Deaconess Medical CenterRecruiting
Brigham and Women's HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Hypoglycemia

Normoglycemia

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT03867344

First Posted

March 4, 2019

Last Updated

July 25, 2023

Sponsor

Brigham and Women's Hospital

Collaborators

Beth Israel Deaconess Medical Center, Boston Children's Hospital, Mclean Hospital

1. Study Identification

Unique Protocol Identification Number

NCT03867344

Brief Title

The Functional Neuroanatomy of the Human Physiological Stress Response

Acronym

Hypo fMRI

Official Title

The Functional Neuroanatomy of the Human Physiological Stress Response

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Recruiting

Study Start Date

October 1, 2019 (Actual)

Primary Completion Date

June 2024 (Anticipated)

Study Completion Date

June 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Brigham and Women's Hospital

Collaborators

Beth Israel Deaconess Medical Center, Boston Children's Hospital, Mclean Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hypoglycemia, Physiological Stress

Keywords

Hypoglycemia, Stress, Brain

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

Participant

Allocation

Randomized

Enrollment

44 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Hypoglycemia

Arm Type

Active Comparator

Arm Description

Arm Title

Normoglycemia

Arm Type

Placebo Comparator

Arm Description

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.

Intervention Type

Other

Intervention Name(s)

Hypoglycemic Hyperinsulinemic Clamp

Other Intervention Name(s)

Hypoglycemic Hyperinsulinemic Clamp Procedure

Intervention Description

Participants undergo a 120-minute hypoglycemic hyperinsulinemic clamp procedure.

Intervention Type

Other

Intervention Name(s)

Normoglycemic Hyperinsulinemic Clamp

Other Intervention Name(s)

Normoglycemic Hyperinsulinemic Clamp Procedure

Intervention Description

Participants undergo a 120-minute normoglycemic hyperinsulinemic clamp procedure.

Primary Outcome Measure Information:

Title

Effect of physiological stress (hypoglycemia) on brain networks involved in autonomic function

Description

Time Frame

Baseline, 8 hours after physiological stress, and 4 days after physiological stress

Title

The relationship over time between stress-induced changes in brain networks and stress-induced changes in baroreflex sensitivity

Description

Time Frame

Baseline, 8 hours after physiological stress, and 4 days after physiological stress

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Healthy volunteers Males and Females age 18 to 45 years BMI 18-35 kg/m2 Exclusion Criteria: Pregnancy Lactation Menopause Any medical condition Current or prior alcohol or drug abuse Active tobacco use 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Gail K Adler, MD, PhD

Phone

617-732-8742

gadler@bwh.harvard.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Roy Freeman, MD

Phone

617-632-8472

rfreeman@bidmc.harvard.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Roy Freeman, MD

Organizational Affiliation

Beth Israel Deaconess Medical Center

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Gail K Adler, MD, PhD

Organizational Affiliation

Brigham and Women's Hospital

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

David Borsook, MD, PhD

Organizational Affiliation

Boston Children's Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Beth Israel Deaconess Medical Center

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Roy Freeman, MD

First Name & Middle Initial & Last Name & Degree

Roy Freeman, MD

Facility Name

Brigham and Women's Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Gail K Adler, MD, PhD

Phone

617-732-6660

Ext

15899

gadler@partners.org

First Name & Middle Initial & Last Name & Degree

Gail K Adler, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

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.

IPD Sharing Time Frame

Data will be shared after completion of study and initial publications which we anticipate to be within 18 months of the final participant completing the study protocol.

IPD Sharing Access Criteria

Access to data must be approved by the IRB at our institution.

Learn more about this trial

The Functional Neuroanatomy of the Human Physiological Stress Response

We'll reach out to this number within 24 hrs