Stress and the Nervous System

NCT02339506 | Completed Results

• 1 other identifier: 2014P002423
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

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.

Conditions

Autonomic Nervous System; Baroreflex; Stress, Physiological

Keywords

stress; ACTH; cosyntropin; baroreflex sensitivity; cardiovagal

Outcome Measures

Primary Outcomes (1)

• 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

Other Outcomes (2)

• Pain (Quantitative Sensory Testing Using a Thermal Pain Testing Device)

  1 day after ACTH

• Hippocampal Memory (Paired Associative Learning Task)

  1 day after ACTH

Study Arms (2)

Cosyntropin

ACTIVE COMPARATOR

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.

Drug: Cosyntropin

Normal saline (Placebo)

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Cosyntropin 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.

Also known as: ACTH

Cosyntropin

Placebo 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.

Also known as: Normal Saline

Normal saline (Placebo)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• Complete blood count
• Serum creatinine, sodium, potassium, glucose, liver enzymes
• Urinalysis
• Urine pregnancy test (if female)
• Normal ECG

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (3)

• 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.

  PMID: 34788228 DERIVED

• 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.

  PMID: 32761088 DERIVED

• 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.

  PMID: 32353115 DERIVED

MeSH Terms

Interventions

Cosyntropin; Adrenocorticotropic Hormone; Saline Solution

Intervention Hierarchy (Ancestors)

Melanocortins; Pro-Opiomelanocortin; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormones, Anterior; Pituitary Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. Gail Kurr Adler
• Organization: Brigham and Women's Hospital

gadler@bwh.harvard.edu

(617) 732-8742

Study Officials

• Gail Adler, MD, PhD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 6, 2015
• First Posted: January 15, 2015
• Study Start: April 1, 2015
• Primary Completion: October 1, 2016
• Study Completion: November 1, 2020
• Last Updated: December 3, 2025
• Results First Posted: November 30, 2017

Record last verified: 2025-11

Locations

US (1)