Over-the-Counter Antihistamines & Heat Stress

NCT06217367 | Unknown Phase 4 FDA Drug

• 2 other identifiers: 100241273752
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (5)

• Whole-Body Sweat Losses

  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

  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

  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

  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

  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 Outcomes (4)

• Thermal Sensation

  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

  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

  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

  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

Study Arms (4)

50 mg Diphenhydramine

EXPERIMENTAL

Drug: 50 mg Diphenhydramine

10 mg Loratadine

EXPERIMENTAL

Drug: 10 mg Loratadine

5 mg Desloratadine

EXPERIMENTAL

Drug: 5 mg Desloratadine

Placebo (Sugar pill)

PLACEBO COMPARATOR

Other: Placebo (Sugar Pill)

Interventions

50 mg Diphenhydramine DRUG

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®

50 mg Diphenhydramine

10 mg Loratadine DRUG

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®

10 mg Loratadine

5 mg Desloratadine DRUG

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®

5 mg Desloratadine

Placebo (Sugar Pill) OTHER

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.

Placebo (Sugar pill)

Eligibility Criteria

• Age: 19 Years - 39 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Lakehead University: lead

Study Sites (1)

Lakehead University C.J Sanders Fieldhouse

Thunder Bay, Ontario, P7B5E1, Canada

RECRUITING

MeSH Terms

Conditions

Heat Stress Disorders; Rhinitis, Allergic; Wounds and Injuries; Drug Hypersensitivity

Interventions

Diphenhydramine; Loratadine; desloratadine; Sugars

Condition Hierarchy (Ancestors)

Rhinitis; Nose Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Otorhinolaryngologic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Ethylamines; Amines; Organic Chemicals; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Cyproheptadine; Dibenzocycloheptenes; Benzocycloheptenes; Polycyclic Aromatic Hydrocarbons; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds; Carbohydrates

Central Study Contacts

Nicholas Ravanelli, PhD

CONTACT

6132630361; nravanel@lakeheadu.ca

Douglas Newhouse, HBK

CONTACT

8076201011; danewho1@lakeheadu.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Participants will be informed of the study interventions prior to experimental trials to ensure participants are able to provide informed consent. However, participants will blinded to the order of the arms (i.e., participants will not be informed which antihistamine/placebo pill they ingest for any trial). Data will remain blinded to researchers until after a third-party statistical analysis.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Assistant Professor

Model Details: 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.

Study Record Dates

• First Submitted: November 8, 2023
• First Posted: January 22, 2024
• Study Start: December 5, 2023
• Primary Completion: June 1, 2024
• Study Completion: June 1, 2024
• Last Updated: January 22, 2024

Record last verified: 2024-01

Locations

CA (1)