Stress and the Nervous System

Not Applicable

• Conditions: Autonomic Nervous System; Baroreflex; Stress, Physiological
• Interventions: Drug: Cosyntropin; Drug: Placebo

• Registration Number: NCT02339506
• Lead Sponsor: Brigham and Women's Hospital

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.

Study Timeline

• Study First Submitted: 2015-01-06
• Study First Submitted QC: 2015-01-12
• Study First Posted: 2015-01-15
• Study Start: 2015-04
• Primary Completion: 2016-10
• Results First Submitted: 2017-09-19
• Results First Submitted QC: 2017-10-25
• Results First Posted: 2017-11-30
• Status Verified: 2022-07
• Last Update Submitted: 2022-07-18
• Last Update Posted: 2022-07-25
• Study Completion: 2023-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 23

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Cosyntropin	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.
Normal saline (Placebo)	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.

Primary Outcome Measures

Name	Time	Method
Cardiovagal Baroreflex Sensitivity (Modified Oxford Technique)	Baseline, 4-hours after infusion, 24-hours after infusion	Cardiovagal baroreflex sensitivity will be measured with the Modified Oxford Technique before, during, and after drug infusions, to evaluate the effects of cosyntropin infusions.

Trial Locations

Locations (1)

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States