Role of Desloratadine in Reducing Inflammation From Occupational Heat Strain

Potential Off-label Use of Desloratadine to Mitigate Inflammation Caused by PPE-induced Heat Stress

The aim of this initial investigational study is to compare the effect of desloratadine on the inflammatory responses to heat stress in firefighters exercising in their personal protective equipment.

Study Overview

• Status: Recruiting
• Conditions: Inflammatory Response; Heat Stress, Exertional; Firefighter Personal Protective Equipment
• Intervention / Treatment: Drug: Desloratadine; Drug: Placebo; Other: No Intervention

Detailed Description

Significant heat strain where temperatures approach and exceed 39.0 degrees celsius is known to increase intestinal permeability and induce a graded systemic inflammatory response which includes increases in interleukin-6, tumor necrosis factor alpha, and c-reactive protein. Recent data examining firefighters found fire service instructors possessed greater resting levels of inflammatory markers and that 18-29% of the variation in these markers could be explained by frequency of heat strain. Firefighters themselves are susceptible to core temperatures ranging between 38.5 and 39.0C in as little as 2-3 work cycles. Considering resource limitation in the fire service, such workloads is a realistic possibility when at structural fires, particularly for first alarm apparatus.

Though there is a well-defined role of the inflammatory response in adaptive changes, elevated resting levels begs the question of whether such frequency of exposure and acute inflammatory flux in fire service workers may contribute to chronic elevations of inflammatory markers and altered disease risk. Elevations in c-reactive protein are associated with cardiovascular risk with studies indicating a causative role of monomeric c-reactive protein in platelet activation and thrombus growth.

Cooling methods save for cryotherapy have demonstrated limited to mild effectiveness for mitigating the inflammatory responses to heat strain resulting in no solution to attenuate acute inflammatory responses. The mast-cell stabilizing properties of desloratadine and its safety profile make it an interesting candidate for investigating its use in this context.

This study seeks to determine whether 10mg desloratadine taken before and 24h after exertional heat strain to a core temperature to a core temperature of 39.5 degrees celsius reduces the associated inflammatory response measured over a 72-hour period.

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Thomas W Service, MSc; Phone Number: 2508964682; Email: service1@uvic.ca

Study Locations

• Canada
  • British Columbia
    • Victoria, British Columbia, Canada, V8P 5C2
      • Recruiting
      • University of Victoria
      • Contact: Thomas W Service, MSc; Phone Number: 2508964682; Email: service1@uvic.ca
      • Contact: Lynneth A Stuart-Hill, PhD; Phone Number: 250-721-7884; Email: lstuhill@uvic.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Demonstrated willingness to participate in the study and adhere to procedures by signing a written informed consent
• Biological males aged 19-50
• Successful Physical Activity Readiness Questionnaire (PAR-Q)
• Ability to swallow core temperature capsule
• VO2Max >35 mL/kg/min
• No allergy or current dosage of H1 histamine receptor antagonists
• Participants must be in good health with no 'Category A' diseases/conditions outlined in National Fire Protection Association (NFPA) 1582 (https://www.iafc.org/docs/default-source/1vcos/vws_rrkit_nfpa-1582.pdf?sfvrsn=ca9b9f0d_2)

Exclusion Criteria:

• Biological females
• Males below age of 19, and 51-years or older
• Unsuccessful PAR-Q
• VO2Max below 35 mL/kg/min
• Allergy to H1 histamine receptor antagonists
• Esophageal constriction (inability to swallow core temperature capsule)
• Any condition or disease listed as 'Category A' in NFPA 1582 that would disqualify a person as a firefighter.
• Current use of NSAIDS or steroid drugs (oral or nasal).
• Consumption of caffeine, nicotine, or alcohol in the preceding 12-hours.
• Dehydration (urine specific gravity over 1.030)
• Recent cold/flu (at least 7-days clear of symptom resolution)
• No use of antibiotics in preceding 14-days.
• Dosing of medication that is known to exhibit adverse reactions with desloratadine dosing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Desloratadine; Desloratadine (Aerius) 10mg compounded to oral pill	Drug: Desloratadine; Oral ingestion 10mg pill 2 hours prior to heat strain trial. Second 10mg dose 24-hours later.; Other Names: Desloratadine (Aerius)
Experimental: Inert Placebo; Placebo 10mg compounded to oral pill	Drug: Placebo; Oral ingestion 10mg inert pill 2 hours prior to heat strain trial. Second dose 24-hours later.; Other Names: Inert Placebo
Experimental: No Intervention; No intervention: neither drug nor placebo	Other: No Intervention; No pill ingestion during the trial - to discern the presence of a placebo effect from baseline inflammatory response; Other Names: Neither Drug nor Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in serum cortisol	Assessment of changes in serum cortisol within and between interventions measured via venipuncture and ELISA	Before, immediately following, and 2-hours following exertional heat strain
Change in serum interleukin-6 and ELISA	Assessment of changes in serum interleukin-6 within and between interventions measured via venipuncture and ELISA	Before, immediately following, and 2-hours following exertional heat strain
Change in serum c-reactive protein	Assessment of changes in serum c-reactive protein within and between interventions measured via venipuncture and ELISA	Before, immediately following, and 24, 48, and 72-hours following exertional heat strain
Change in serum tumor necrosis factor alpha	Assessment of changes in serum tumor necrosis factor alpha within and between interventions measured via venipuncture and ELISA.	Before, immediately following, and 2-hours following exertional heat strain

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in body mass	Trial arm differences in fluid loss estimated via differences between before-after body mass.	Before and immediately after exertional heat strain
Differences in core body heat storage	Trial arm differences in the change in core body temperature during heating.	Before and immediately after exertional heat strain

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in Cerebral Blood Flow	Within and between intervention differences in cerebral blood flow changes via vascular duplex ultrasound and hypercapnia	Before and immediately after (following assessment of outcome 8 and 9) exertional heat strain
Differences in heart rate (HR) and heart rate variability (HRV)	Within and between intervention differences in HR and HRV	Before and immediately after exertional heat strain
Differences in brain blood oxygenation of prefrontal cortex	Within and between intervention differences in prefrontal cortex oxygenation via near-infrared spectroscopy	Before and immediately after exertional heat strain

Collaborators and Investigators

• Sponsor: University of Victoria
• Investigators: Principal Investigator: Lynneth Stuart-Hill, PhD, University of Victoria

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2022
• Primary Completion (Anticipated): August 1, 2023
• Study Completion (Anticipated): August 1, 2023

Study Registration Dates

• First Submitted: June 13, 2022
• First Submitted That Met QC Criteria: July 4, 2022
• First Posted (Actual): July 6, 2022

Study Record Updates

• Last Update Posted (Actual): July 6, 2022
• Last Update Submitted That Met QC Criteria: July 4, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Wounds and Injuries; Inflammation; Heat Stress Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Antagonists; Cholinergic Agents; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Histamine H1 Antagonists, Non-Sedating; Desloratadine
• Other Study ID Numbers: 21-0616

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Data, if used in a publication, may be available in a data repository with all identifiers removed.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No