The Functional Neuroanatomy of the Human Physiological Stress Response

NCT03867344 | Completed DMC

• 1 other identifier: 2019P000318
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 2

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.

Conditions

Hypoglycemia; Physiological Stress

Keywords

Hypoglycemia; Stress; Brain

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

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

Study Arms (2)

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.

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.

Other: Normoglycemic Hyperinsulinemic Clamp

Interventions

Hypoglycemic Hyperinsulinemic Clamp OTHER

Participants undergo a 120-minute hypoglycemic hyperinsulinemic clamp procedure.

Also known as: Hypoglycemic Hyperinsulinemic Clamp Procedure

Hypoglycemia

Normoglycemic Hyperinsulinemic Clamp OTHER

Participants undergo a 120-minute normoglycemic hyperinsulinemic clamp procedure.

Also known as: Normoglycemic Hyperinsulinemic Clamp Procedure

Normoglycemia

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy volunteers
• Males and Females age 18 to 45 years
• BMI 18-35 kg/m2

You may not qualify if:

• 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

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Beth Israel Deaconess Medical Center: collaborator
• Boston Children's Hospital: collaborator
• Mclean Hospital: collaborator

Study Sites (2)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Hypoglycemia

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Roy Freeman, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

• Gail K Adler, MD, PhD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

• David Borsook, MD, PhD

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 4, 2019
• First Posted: March 8, 2019
• Study Start: October 1, 2019
• Primary Completion: December 30, 2025
• Study Completion: December 30, 2025
• Last Updated: January 5, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• 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.
• Access Criteria: Access to data must be approved by the IRB at our institution.

Locations

US (2)