Clinical trial NCT06217367: Over-the-Counter Antihistamines & Heat Stress
Official title: Do Common Over-the-counter Antihistamine Medications Modify Thermoregulatory Responses During Passive Heat Stress?
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: 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
Lead sponsor: Lakehead University
Sponsor class: OTHER
First posted: 2024-01-22
Enrollment: 16
Sex: ALL
Minimum age (years): 19
Maximum age (years): 39
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Each participant will be asked to ingest either i) 50mg of diphenhydramine, ii) 10 mg loratadine iii) 5 mg desloratadine, or iv) placebo (sugar pill) \~2 hours before heating protocol in a random pre-determined order over four separate experimental trials.
Primary purpose: OTHER

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Whole-Body Sweat Losses
timeFrame: For each study arm (all completed within 4 months), measurements taken immediately before heating protocol & immediately following the heating protocol
measure: Skin Blood Flow
timeFrame: 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
measure: Heart Rate
timeFrame: 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
measure: Mean Arterial Pressure
timeFrame: 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
measure: Local Sweat Rate
timeFrame: 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:
measure: Thermal Sensation
timeFrame: 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
measure: Thermal Comfort
timeFrame: 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
measure: Mental Acuity
timeFrame: 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
measure: Sleepiness/Fatigue level
timeFrame: 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
Other outcomes:
Locations:
city: Thunder Bay
country: Canada
facility: Lakehead University C.J Sanders Fieldhouse
state: Ontario
Study officials:
References: