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RecruitingNCT06217367Updated Jan 22, 2024

Over-the-Counter Antihistamines & Heat Stress

A Phase 4 interventional study of 50 mg Diphenhydramine and 10 mg Loratadine in Heat Illness, Allergic Rhinitis and Heat Injury, sponsored by Lakehead University. Recruiting at 1 site in Canada. Open to participants aged 19 Years to 39 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-01-22.

Sponsored by Lakehead University · Phase 4, Interventional, and Other

Phase
Phase 4
Study type
Interventional
Enrollment
16
Allocation
Randomized
Ages
19 Years to 39 Years
Sex
All
01

Study summary

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.

02

Conditions studied

  • Heat Illness
  • Allergic Rhinitis
  • Heat Injury
  • Sudomotor Sympathetic Dysfunction

Keywords

  • H1 antihistamine
  • Sweating
  • Heat stress
  • Thermoregulation
  • M3 Muscarinic receptors
  • H1 receptor antagonism
  • M3 Muscarinic receptor blockade
  • Heat Illness/Injury
  • Allergic Rhinitis
  • Over-the-counter antihistamines
  • Allergy medication
03

Who can participate

Ages eligible
19 Years to 39 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

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

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
04

Study design

Phase
Phase 4
Primary purpose
Other
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Double (Participant, Investigator)
Enrollment
16 participants (estimated)

Study arms

  • Experimental
    50 mg Diphenhydramine

    Drug: 50 mg Diphenhydramine

  • Experimental
    10 mg Loratadine

    Drug: 10 mg Loratadine

  • Experimental
    5 mg Desloratadine

    Drug: 5 mg Desloratadine

  • Placebo comparator
    Placebo (Sugar pill)

    Other: Placebo (Sugar Pill)

Interventions

  • Drug50 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.

    Also known as: Benadryl®

  • Drug10 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.

    Also known as: Claritin®

  • Drug5 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.

    Also known as: Aerius®

  • OtherPlacebo (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.

05

What researchers measure

Primary outcomes

  1. Whole-Body Sweat Losses

    Difference in participants' pre/post body mass

    Time frame: For each study arm (all completed within 4 months), measurements taken immediately before heating protocol & immediately following the heating protocol

  2. Skin Blood Flow

    Measured using laser-doppler skin blood blow sensor affixed to forearm

    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

  3. Heart Rate

    Measured using electrocardiogram

    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

  4. Mean Arterial Pressure

    Measured using brachial blood pressure cuff

    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

  5. Local Sweat Rate

    Measured using ventilated sweat capsules affixed to forearm and chest

    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

Secondary outcomes

  1. Thermal Sensation

    Self-assessments of thermal sensation using a 7-point analog scale where -3 is "Cold" and +3 is "Hot".

    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

  2. Thermal Comfort

    Self-assessments of thermal comfort using four-point analog scale where 1 is "Not uncomfortable" and 4 is "Very uncomfortable"

    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

  3. Mental Acuity

    Indexed with digital Stroop test

    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

  4. Sleepiness/Fatigue level

    Measured using Stanford Sleepiness Scale (min: 1, max: 7 (more fatigued))

    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

06

Study locations

1 of 1 sites recruiting
  • Lakehead University C.J Sanders Fieldhouse
    Thunder Bay, Ontario P7B5E1, Canada
    • Nicholas Ravanelli, PhD · Contact · nravanel@lakeheadu.ca · 6132630361
    • Nicholas Ravanelli, PhD · Principal investigator
    • Douglas Newhouse, HBK · Sub investigator
    • Mario Nucci, MD · Sub investigator
    Recruiting
07

Registry details

Key details

Study ID
NCT06217367
Lead sponsor
Lakehead University
Responsible party
Nicholas Ravanelli (Principal Investigator, Assistant Professor, Lakehead University) — Principal investigator
First posted
Jan 22, 2024
Start date
Dec 5, 2023
Primary completion
Jun 2024 (estimated)
Completion
Jun 2024 (estimated)
Last update
Jan 22, 2024

Study contacts

Nicholas Ravanelli, PhD
Contact
nravanel@lakeheadu.ca
6132630361
Douglas Newhouse, HBK
Contact
danewho1@lakeheadu.ca
8076201011

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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