Over-the-Counter Antihistamines & Heat Stress

Lakehead University

Status and phase: Enrolling; Phase 4

Conditions: Allergic Rhinitis; Heat Injury; Sudomotor Sympathetic Dysfunction; Heat Illness

Treatments: Drug: 10 mg Loratadine; Other: Placebo (Sugar Pill); Drug: 50 mg Diphenhydramine; Drug: 5 mg Desloratadine

Study type: Interventional

Funder types: Other

Identifiers

NCT06217367

273752 (Registry Identifier)

100241

Details and patient eligibility

About

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.

Enrollment: 16 estimated patients

Sex: All

Ages: 19 to 39 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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16 participants in 4 patient groups, including a placebo group

50 mg Diphenhydramine

Experimental group

Treatment:

Drug: 50 mg Diphenhydramine

10 mg Loratadine

Experimental group

Treatment:

Drug: 10 mg Loratadine

5 mg Desloratadine

Experimental group

Treatment:

Drug: 5 mg Desloratadine

Placebo (Sugar pill)

Placebo Comparator group

Treatment:

Other: Placebo (Sugar Pill)