Stress and the Nervous System

Stress, Physiological Clinical Trial

Official title:

Stress and the Nervous System

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02339506
• Other study ID #: 2014P002423
• Status: Active, not recruiting
• Phase: N/A
• Start date: April 2015
• Est. completion date: December 2023

Study information

• Verified date: July 2022
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 23
• Est. completion date: December 2023
• Est. primary completion date: October 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Autonomic Nervous System
• Baroreflex
• Stress, Physiological

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	Beth Israel Deaconess Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pain (Quantitative Sensory Testing Using a Thermal Pain Testing Device)	Alterations in pain sensing will be evaluated pre and post with quantitative sensory testing using a thermal pain testing device, to evaluate the delayed effect of cosyntropin infusions.	1 day after ACTH
Other	Hippocampal Memory (Paired Associative Learning Task)	Hippocampal memory will be evaluated pre and post with a paired associative learning task. Face Name Associative Memory Exam (FNAME) composite score on a scale from 0-36, with 36 being the best possible score.	1 day after ACTH
Primary	Cardiovagal Baroreflex Sensitivity (Modified Oxford Technique)	Cardiovagal baroreflex sensitivity will be measured with the Modified Oxford Technique before, during, and after drug infusions, to evaluate the effects of cosyntropin infusions.	Baseline, 4-hours after infusion, 24-hours after infusion