The Effects of Propranolol, Hydrocortisone, and Morphine on Military-Relevant Performance Outcomes

NCT06982183 | Recruiting Phase 4 FDA Drug

• 2 other identifiers: WRAIR #2950MO210072
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial aims to evaluate the nature and duration of effects of three FDA-approved medications (propranolol, hydrocortisone, and morphine) on military-relevant cognitive, emotional, and motor performance following an exposure to a stressful situation (i.e., exposure to a tarantula) in physically healthy adult volunteers (aged 18 - 40) with fear of spiders to help the future development of medications for treating Acute Stress Reactions. The main questions this study aims to answer are: Will placebo treatment (oral placebo) result in significant decrements in Psychomotor Vigilance Task (PVT) performance compared to propranolol treatment? Will placebo treatment \[intramuscular (IM) placebo\] result in significant decrements in PVT performance compared to hydrocortisone treatment? Will placebo treatment (IM placebo) result in significant decrements in PVT performance compared to morphine treatment? Participants will receive one of five study medications (oral propranolol, oral placebo, IM hydrocortisone, IM morphine, or IM morphine) after a brief exposure to a tarantula. Participants will complete cognitive and simple motor tasks and psychological assessments before and after the study medication administration.

Conditions

Fear of Spiders; Acute Stress Reaction

Keywords

Fear of Spiders; morphine; propranolol; hydrocortisone; randomized controlled trial; neuropsychological tests; acute stress reaction

Outcome Measures

Primary Outcomes (1)

• Psychomotor Vigilance Task

  Measure of cognitive performance. Reaction time (millisecond)

  Baseline and post-treatment time points within approximately 25 hours following the study medication administration.

Secondary Outcomes (14)

• Behavioral Approach Task

  Baseline and approximately 24 hours post-treatment.

• Go/No-Go task

  Baseline and post-treatment time points within approximately 25 hours following the study medication administration.

• Matching to Sample task

  Baseline and post-treatment time points within approximately 25 hours following the study medication administration.

• Simple Reaction Time task

  Baseline and post-treatment time points within approximately 25 hours following the study medication administration.

• The Automated Neuropsychological Assessment Metrics (ANAM) Mood Scale

  Baseline and post-treatment time points within approximately 25 hours following the study medication administration.

Study Arms (5)

Propranolol (oral)

ACTIVE COMPARATOR

Drug: Propranolol

Placebo (oral)

PLACEBO COMPARATOR

Drug: Placebo (oral)

Hydrocortisone (IM)

ACTIVE COMPARATOR

Drug: Hydrocortisone

Morphine (IM)

ACTIVE COMPARATOR

Drug: Morphine

Placebo (IM)

PLACEBO COMPARATOR

Drug: Placebo (IM)

Interventions

Propranolol DRUG

An administration of a 40-mg propranolol capsule immediately after tarantula exposure

Propranolol (oral)

Hydrocortisone DRUG

An intramuscular administration of 62.5 mg/1 ml of hydrocortisone immediately after tarantula exposure

Hydrocortisone (IM)

Morphine DRUG

An intramuscular administration of 5 mg/1 ml of morphine immediately after tarantula exposure

Morphine (IM)

Placebo (oral) DRUG

An administration of a placebo capsule after tarantula exposure

Placebo (oral)

Placebo (IM) DRUG

An intramuscular administration of 1 ml of saline immediately after tarantula exposure

Placebo (IM)

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male and non-pregnant, non-lactating females 18 to 40 (inclusive) years of age.
• Females of child-bearing potential must be on some form of birth control, if sexually active (e.g., oral contraceptive, condom, intrauterine device, etc.)
• Score of 80% or greater on a "Volunteer Comprehension Assessment" test.
• Score equal to or greater than 54 on the Fear of Spiders Questionnaire.
• Body weight between 91 and 250 pounds (inclusive).
• Live close enough to be able to commute to Walter Reed Army Institute of Research during the study participation.

You may not qualify if:

• Contraindications due to study medications, including a history of allergic/hypersensitivity reactions to a beta blocker, an opiate agonist or a steroid, or a history of other adverse reactions to these classes of drugs (such as an episode of steroid psychosis).
• A history of allergic reactions to a spider bite.
• A history of abuse or addiction to illicit drugs (including marijuana) or prescribed medication (e.g., opioid) (diagnosed or suspected based on the medical history).
• Use a nicotine product (e.g., cigarette, cigar, vape) more than 3 days per week.
• Self-reported caffeine use in excess of 600 mg (e.g., approximately 10 caffeinated sodas or approximately 29 ounces of brewed coffee) per day on average or not being able to go without caffeine during the In-Lab visits.
• Score of 10 or above on the Beck Depression Inventory (BDI) or a score of \> 0 on item 9 "Suicidal Thoughts or Wishes" of the BDI
• Score of 41 or above on the State-Trait Anxiety Inventory - Trait (STAI-T).
• Score of 20 or above on the PROMIS Emotional Distress - Anxiety - Short Form.
• Score of 33 or above on the PTSD Checklist, 5th Edition (PCL-5)
• History of cardiovascular disease (to include but not limited to arrhythmias, valvular heart disease, congestive heart failure, history of sudden cardiac death or myocardial infarction).
• A history of asthma or any type of reactive airways disease or any acute or chronic pulmonary disorder that could lead to a compromise of blood oxygenation in the setting of a modest reduction in tidal volume or respiratory rate, to include neuromuscular disorders.
• Regularly work night shifts or have a habitual sleep/wake schedule that is not conducive to compliance with the recommended sleep time (11:00 pm - 6:00 am) during participation (e.g., extremely early or late habitual bedtime or rise time, to be determined on a case-by-case basis by the principal investigator or an associate investigator).
• A diagnosis of sleep apnea.
• Kidney disease or kidney abnormalities, liver disease or liver abnormalities, or any other metabolic derangements (endocrine disorders, hyperglycemia, etc.) that could alter neurophysiological function.
• Liver disease or significant liver abnormalities as determined by examining study medical investigator.

Sponsors & Collaborators

• Walter Reed Army Institute of Research (WRAIR): lead

Study Sites (1)

Sleep Research Center (SRC), Walter Reed Army Institute of Research

Silver Spring, Maryland, 20910, United States

RECRUITING

MeSH Terms

Conditions

Arachnophobia; Stress Disorders, Traumatic, Acute

Interventions

Propranolol; Hydrocortisone; Morphine

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes

Central Study Contacts

John Hughes, MD

CONTACT

301-319-3214; john.d.hughes4.civ@health.mil

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2025
• First Posted: May 21, 2025
• Study Start: May 27, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: July 15, 2025

Record last verified: 2025-07

Locations

US (1)