Stress and the Nervous System

NCT ID: NCT02339506

Last Updated: 2025-12-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-30
• Study Completion Date: 2020-11-30

Brief Summary

Models of stress such as hypoglycemia have identified that stress results the next day in decreased baroreflex sensitivity. This project will test the hypothesis that these delayed changes in autonomic nervous system function are secondary to a rise in ACTH. The investigators will infuse cosyntropin versus placebo in a double-blind, crossover study in healthy adults and measure the delayed effects on the autonomic system as measured by cardiovagal baroreflex sensitivity.

Detailed Description

Stress has complex effects on the body's physiology. Models of stress such as hypoglycemia have identified that stress activates the hypothalamic-pituitary-adrenal (HPA) axis and sympathoadrenal system acutely. Additionally, there are delayed effects of prior exposure to hypoglycemia. The day after being exposed to a hypoglycemic stimulus there are: 1) decreases in the catecholamine release to a new hypoglycemic stress; 2) decreases in the muscle sympathetic nerve activity (MSNA) response to either a new hypoglycemic challenge or transient hypotension; 3) decreases in cardiac vagal baroreflex sensitivity (BRS); and 4) increases in sensitivity to thermal pain and altered temporal summation (decreased tolerance to a repeated minimally painful stimulus). This project will test the hypothesis that these delayed changes in autonomic nervous system function are secondary to a rise in ACTH that occurs in response to stress.

Primary Aim. Infusion of ACTH (cosyntropin) will lead the next day to decreased cardiovagal baroreflex sensitivity in healthy subjects.

Conditions

Autonomic Nervous System; Baroreflex; Stress, Physiological

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: TRIPLE

Study Groups

Cosyntropin

Subjects will receive cosyntropin infusion at 70 mcg/hr for two sessions of 2.5 hours each on day 2 of a three day admission to our research center.

Group Type: ACTIVE_COMPARATOR

Cosyntropin

Intervention Type: DRUG

Subjects will receive cosyntropin at 70 mcg/hr for two sessions of 2.5 hours each on day 2 of a three day admission to our research center.

Normal saline (Placebo)

Subjects will receive normal saline infusion for two sessions of 2.5 hours each on day 2 of a three day admission to our research center.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Subjects will receive placebo (normal saline infusion) for two sessions of 2.5 hours each on day 2 of a three day admission to our research center.

Interventions

Cosyntropin

Subjects will receive cosyntropin at 70 mcg/hr for two sessions of 2.5 hours each on day 2 of a three day admission to our research center.

Intervention Type: DRUG

Placebo

Subjects will receive placebo (normal saline infusion) for two sessions of 2.5 hours each on day 2 of a three day admission to our research center.

Intervention Type: DRUG

Other Intervention Names

ACTH; Normal Saline

Eligibility Criteria

Inclusion Criteria

Subjects must be currently healthy, BMI 18-32 kg/m2, and not be on any medications.

This study will recruit men and women. Due to concerns about estrogen's effects on hormone levels and possible contributions of menstrual symptoms on pain sensing thresholds, we will schedule the inpatient studies to avoid the early follicular phase in normally cycling women.

Subjects must have normal laboratory values for:

1. Complete blood count

2. Serum creatinine, sodium, potassium, glucose, liver enzymes

3. Urinalysis

4. Urine pregnancy test (if female)

5. Normal ECG

Exclusion Criteria

We will exclude individuals with:

• Systolic blood pressure > 140 or < 90 mm Hg
• Diastolic blood pressure > 90 mm Hg
• Creatinine clearance ≤ 60 mL/min, as calculated by MDRD formula
• Known DM, CHF, CAD, PVD, CVA, MI, asthma
• Known or history of Cushing's disease or adrenal insufficiency
• Known neurologic disease
• Known psychiatric disease
• Steroid use (oral or inhaled, local or systemic injections, within the past 6 months)
• Significant concomitant medical illnesses
• Current excessive alcohol (>10oz ethanol/week)
• Current use of recreational drugs
• Current smokers
• Current pregnancy
• Chronic use of non-steroidal anti-inflammatory or narcotic medications
• Evidence of ischemia or heart block on screening electrocardiogram (greater than type I-second degree heart block, left bundle branch block, or ST-T wave changes in 2 or more contiguous leads)
• Subjects taking any prescription medications (other than oral birth control pills) or herbal medications will be excluded.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role: collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Gail Kurr Adler

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gail Adler, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Brigham and Women's Hospital

Boston, Massachusetts, United States

Countries

United States

References

Zaheer S, Meyer K, Easly R, Bayomy O, Leung J, Koefoed AW, Heydarpour M, Freeman R, Adler GK. Effect of adrenocorticotropic hormone infusion on circulating sclerostin levels. Endocr Connect. 2021 Dec 14;10(12):1607-1614. doi: 10.1530/EC-21-0263.

Reference Type: DERIVED

PMID: 34788228 (View on PubMed)

van der Boom T, Jia C, Lefrandt JD, Connelly MA, Links TP, Tietge UJF, Dullaart RPF. HDL Cholesterol Efflux Capacity is Impaired in Severe Short-Term Hypothyroidism Despite Increased HDL Cholesterol. J Clin Endocrinol Metab. 2020 Sep 1;105(9):e3355-62. doi: 10.1210/clinem/dgaa411.

Reference Type: DERIVED

PMID: 32761088 (View on PubMed)

Leung JH, Bayomy OF, Bonyhay I, Celli J, White J, Freeman R, Adler GK. ACTH Infusion Impairs Baroreflex Sensitivity-Implications for Cardiovascular Hypoglycemia-Associated Autonomic Failure. J Clin Endocrinol Metab. 2020 Jul 1;105(7):2345-53. doi: 10.1210/clinem/dgaa221.

Reference Type: DERIVED

PMID: 32353115 (View on PubMed)

Other Identifiers

2014P002423

Identifier Type: -

Identifier Source: org_study_id