The Functional Neuroanatomy of the Human Physiological Stress Response

NCT ID: NCT03867344

Last Updated: 2026-01-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-01
• Study Completion Date: 2025-12-30

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.

Conditions

Hypoglycemia; Physiological Stress

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Hypoglycemia

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.

Group Type: ACTIVE_COMPARATOR

Hypoglycemic Hyperinsulinemic Clamp

Intervention Type: OTHER

Participants undergo a 120-minute hypoglycemic hyperinsulinemic clamp procedure.

Normoglycemia

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.

Group Type: PLACEBO_COMPARATOR

Normoglycemic Hyperinsulinemic Clamp

Intervention Type: OTHER

Participants undergo a 120-minute normoglycemic hyperinsulinemic clamp procedure.

Interventions

Hypoglycemic Hyperinsulinemic Clamp

Participants undergo a 120-minute hypoglycemic hyperinsulinemic clamp procedure.

Intervention Type: OTHER

Normoglycemic Hyperinsulinemic Clamp

Participants undergo a 120-minute normoglycemic hyperinsulinemic clamp procedure.

Intervention Type: OTHER

Other Intervention Names

Hypoglycemic Hyperinsulinemic Clamp Procedure; Normoglycemic Hyperinsulinemic Clamp Procedure

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role: collaborator

Boston Children's Hospital

OTHER

Sponsor Role: collaborator

Mclean Hospital

OTHER

Sponsor Role: collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Gail Kurr Adler

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Roy Freeman, MD

Role: PRINCIPAL_INVESTIGATOR

Beth Israel Deaconess Medical Center

Gail K Adler, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

David Borsook, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Boston Children's Hospital

Locations

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

2019P000318

Identifier Type: -

Identifier Source: org_study_id