Over-the-Counter Antihistamines & Heat Stress

January 11, 2024 updated by: Nicholas Ravanelli, Lakehead University

Do Common Over-the-counter Antihistamine Medications Modify Thermoregulatory Responses During Passive Heat Stress?

Allergic rhinitis (AR) currently affects ~25% of Canadians, and due to factors of climate change, this number is expected to increase over the coming decade. AR symptoms can significantly impact individuals' quality of life by compromising sleep, productivity, and social interactions. To alleviate AR symptoms, North Americans tend to rely on H1 antihistamine medications available over-the-counter (OTC) at most pharmacies. However, public health authorities currently suggest restraining all antihistamines during heat waves due to beliefs that M3 muscarinic receptor and H1 receptor antagonism, independent pharmacological mechanisms of H1 antihistamines, might suppress thermoregulatory responses to heat stress and increase individuals' susceptibility to heat-related illness/injury. To date, studies using supramaximal doses of antihistamines have demonstrated reductions in sweating, however these doses and administration routes are not the typical use case. Additional studies utilizing fexofenadine, a second-generation H1 antihistamine, have linked H1 receptor antagonism to reductions in skin blood flow, potentially impacting thermoregulation by reducing peripheral blood redistribution. Empirical evidence supporting OTC H1 antihistamines impacting thermoregulatory control at recommended doses is scarce. Thus, this study aims to systematically assess whether three common OTC H1 antihistamines, taken as prescribed, alter thermoregulatory responses during thermal stress.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

16

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Ontario
      • Thunder Bay, Ontario, Canada, P7B5E1
        • Recruiting
        • Lakehead University C.J Sanders Fieldhouse
        • Contact:
        • Principal Investigator:
          • Nicholas Ravanelli, PhD
        • Sub-Investigator:
          • Douglas Newhouse, HBK
        • Sub-Investigator:
          • Mario Nucci, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Male or Female between ages 19 and 39 years
  • Fully vaccinated against COVID-19
  • Able to provide informed consent
  • Body-mass index under 30

Exclusion Criteria:

  • Body-mass index over 30
  • Currently taking sedative or autonomic nervous system depressant medication
  • Hypersensitivity to diphenhydramine, loratadine, or desloratadine
  • History of cardiovascular disease, cancer, type 1 or 2 diabetes, chronic obstructive pulmonary disorder, or cystic fibrosis
  • Have smoked tobacco products less than 12 months prior to participation
  • Pregnant/Breastfeeding

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 50 mg Diphenhydramine
Drug: 50 mg Diphenhydramine
Participants ingest 50mg of diphenhydramine orally ~2 hours prior to a passive heating protocol. Participants then don a water-perfusion heat suited and lay supine on assessment table while 49℃ is circulated throughout the garment. Heating persists until participants reach a 1.5℃ increase in core temperature from baseline.
Other Names:
  • Benadryl®
Experimental: 10 mg Loratadine
Drug: 10 mg Loratadine
Participants ingest 10 mg of loratadine orally ~2 hours prior to a passive heating protocol. Participants then don a water-perfusion heat suited and lay supine on assessment table while 49℃ is circulated throughout the garment. Heating persists until participants reach a 1.5℃ increase in core temperature from baseline.
Other Names:
  • Claritin®
Experimental: 5 mg Desloratadine
Drug: 5 mg Desloratadine
Participants ingest 5 mg of desloratadine orally ~2 hours prior to a passive heating protocol. Participants then don a water-perfusion heat suited and lay supine on assessment table while 49℃ is circulated throughout the garment. Heating persists until participants reach a 1.5℃ increase in core temperature from baseline.
Other Names:
  • Aerius®
Placebo Comparator: Placebo (Sugar pill)
Other: Placebo (Sugar Pill)
Participants ingest placebo pill orally ~2 hours prior to a passive heating protocol. Participants then don a water-perfusion heat suited and lay supine on assessment table while 49℃ is circulated throughout the garment. Heating persists until participants reach a 1.5℃ increase in core temperature from baseline.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Whole-Body Sweat Losses
Time Frame: For each study arm (all completed within 4 months), measurements taken immediately before heating protocol & immediately following the heating protocol
Difference in participants' pre/post body mass
For each study arm (all completed within 4 months), measurements taken immediately before heating protocol & immediately following the heating protocol
Skin Blood Flow
Time Frame: For each study arm (all completed within 4 months), measured before heating, and at every 0.25C increase in core temperature (+0.25C, +0.50C, +0.75C, +1.0C, +1.25C, and +1.5C), or every ~15 minutes of (up to ~90 minutes) and immediately after heating
Measured using laser-doppler skin blood blow sensor affixed to forearm
For each study arm (all completed within 4 months), measured before heating, and at every 0.25C increase in core temperature (+0.25C, +0.50C, +0.75C, +1.0C, +1.25C, and +1.5C), or every ~15 minutes of (up to ~90 minutes) and immediately after heating
Heart Rate
Time Frame: For each study arm (all completed within 4 months), measured before heating, and at every 0.25C increase in core temperature (+0.25C, +0.50C, +0.75C, +1.0C, +1.25C, and +1.5C), or every ~15 minutes of (up to ~90 minutes) and immediately after heating
Measured using electrocardiogram
For each study arm (all completed within 4 months), measured before heating, and at every 0.25C increase in core temperature (+0.25C, +0.50C, +0.75C, +1.0C, +1.25C, and +1.5C), or every ~15 minutes of (up to ~90 minutes) and immediately after heating
Mean Arterial Pressure
Time Frame: For each study arm (all completed within 4 months), measurements taken at baseline before heating, and every 10 minutes throughout heating protocol (up to ~ 90 minutes), and immediately after heating
Measured using brachial blood pressure cuff
For each study arm (all completed within 4 months), measurements taken at baseline before heating, and every 10 minutes throughout heating protocol (up to ~ 90 minutes), and immediately after heating
Local Sweat Rate
Time Frame: For each study arm (all completed within 4 months), measured before heating, and at every 0.25C increase in core temperature (+0.25C, +0.50C, +0.75C, +1.0C, +1.25C, and +1.5C), or every ~15 minutes of (up to ~90 minutes) and immediately after heating
Measured using ventilated sweat capsules affixed to forearm and chest
For each study arm (all completed within 4 months), measured before heating, and at every 0.25C increase in core temperature (+0.25C, +0.50C, +0.75C, +1.0C, +1.25C, and +1.5C), or every ~15 minutes of (up to ~90 minutes) and immediately after heating

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Thermal Sensation
Time Frame: For each study arm (all completed within 4 months), measured before heating, and at every 0.25C increase in core temperature (+0.25C, +0.50C, +0.75C, +1.0C, +1.25C, and +1.5C), or every ~15 minutes of (up to ~90 minutes) and immediately after heating
Self-assessments of thermal sensation using a 7-point analog scale where -3 is "Cold" and +3 is "Hot".
For each study arm (all completed within 4 months), measured before heating, and at every 0.25C increase in core temperature (+0.25C, +0.50C, +0.75C, +1.0C, +1.25C, and +1.5C), or every ~15 minutes of (up to ~90 minutes) and immediately after heating
Thermal Comfort
Time Frame: For each study arm (all completed within 4 months), measured before heating, and at every 0.25C increase in core temperature (+0.25C, +0.50C, +0.75C, +1.0C, +1.25C, and +1.5C), or every ~15 minutes of (up to ~90 minutes) and immediately after heating
Self-assessments of thermal comfort using four-point analog scale where 1 is "Not uncomfortable" and 4 is "Very uncomfortable"
For each study arm (all completed within 4 months), measured before heating, and at every 0.25C increase in core temperature (+0.25C, +0.50C, +0.75C, +1.0C, +1.25C, and +1.5C), or every ~15 minutes of (up to ~90 minutes) and immediately after heating
Mental Acuity
Time Frame: For each study arm (all completed within 4 months), measurements taken 2 hours before heating (pre-pill ingestion), 5-minutes before initiating heating, and within 5-minutes after the heating protocol
Indexed with digital Stroop test
For each study arm (all completed within 4 months), measurements taken 2 hours before heating (pre-pill ingestion), 5-minutes before initiating heating, and within 5-minutes after the heating protocol
Sleepiness/Fatigue level
Time Frame: For each study arm (all completed within 4 months), measurements taken 2 hours before heating (pre-pill ingestion), 5-minutes before initiating heating, and within 5-minutes after the heating protocol
Measured using Stanford Sleepiness Scale (min: 1, max: 7 (more fatigued))
For each study arm (all completed within 4 months), measurements taken 2 hours before heating (pre-pill ingestion), 5-minutes before initiating heating, and within 5-minutes after the heating protocol

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Lakehead University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 5, 2023

Primary Completion (Estimated)

June 1, 2024

Study Completion (Estimated)

June 1, 2024

Study Registration Dates

First Submitted

November 8, 2023

First Submitted That Met QC Criteria

January 11, 2024

First Posted (Actual)

January 22, 2024

Study Record Updates

Last Update Posted (Actual)

January 22, 2024

Last Update Submitted That Met QC Criteria

January 11, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 100241
  • 273752 (Registry Identifier: Health Canada, Control Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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