Diphenhydramine and Sweating (BENEXE2022)

Does Diphenhydramine Alter Thermoregulatory Responses During Exercise?

In 2012, it was estimated that nearly 1 in 4 Canadians suffer from allergic rhinitis. To add, 78% of individuals working in predisposing environments are predicted to develop occupational rhinitis. Currently, the most popular treatment for rhinitis is antihistamine medication such as diphenhydramine, a first-generation antihistamine sold commercially as Benadryl®. Due it its anticholinergic effects, diphenhydramine has been suggested to impair the whole body sweating response during heat stress, potentially leaving consumers at an increased risk of heat-related illness. This randomized control trial approved by Health Canada will investigate whether ingesting extra strength diphenhydramine (50mg) will alter whole-body sweat losses during 60 minutes of exercise.

Study Overview

• Status: Completed
• Conditions: Hyperthermia; Allergic Rhinitis; Diphenhydramine Causing Adverse Effects in Therapeutic Use; Sweating
• Intervention / Treatment: Drug: Placebo; Drug: Diphenhydramine

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Thunder Bay, Ontario, Canada, P7B 5E1
      • Lakehead Unviersity

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Able to safely perform ~60 minutes of moderate intensity exercise
• No known hypersensitivity to diphenhydramine
• Not on any prescribed medication
• Body-mass index (BMI) less than 30

Exclusion Criteria:

• Outside 18 - 49 years of age
• Diagnosed with any cardiovascular, respiratory, neurological or metabolic disease
• History of any cardiovascular, respiratory, neurological or metabolic disease
• Unable to exercise for 60 minutes at moderate intensity, or have a musculoskeletal injury
• BMI > or = 30

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Intervention Order (Placebo - Diphenhydramine); On separate days, participants will march on a treadmill for 60 minutes at a fixed rate of oxygen consumption (~1.75 liters of oxygen consumption per minute) in ~28°C and 30% relative humidity	Drug: Placebo; A placebo pill (i.e., sugar) will be consumed 2 h before intervention.; Drug: Diphenhydramine; Extra strength Benadryl (DIN 02470144) will be consumed 2 h before intervention
Other: Intervention Order (Diphenhydramine -Placebo); On separate days, participants will march on a treadmill for 60 minutes at a fixed rate of oxygen consumption (~1.75 liters of oxygen consumption per minute) in ~28°C and 30% relative humidity	Drug: Placebo; A placebo pill (i.e., sugar) will be consumed 2 h before intervention.; Drug: Diphenhydramine; Extra strength Benadryl (DIN 02470144) will be consumed 2 h before intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Whole body sweat loss	Change in body mass from pre- to post-exercise corrected for respiratory and metabolic water losses using a digital platform scale accurate to +/- 2 grams.	Measured during both placebo and diphenhydramine intervention trials trials, separated by no more than 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in rectal temperature	Change in rectal temperature from pre- to post- exercise using a pediatric grade thermistor	Measured during both placebo and diphenhydramine intervention trials trials, separated by no more than 28 days

Collaborators and Investigators

• Sponsor: Lakehead University
• Investigators: Principal Investigator: Nicholas Ravanelli, PhD, Lakehead University

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2022
• Primary Completion (Actual): June 23, 2023
• Study Completion (Actual): June 23, 2023

Study Registration Dates

• First Submitted: October 14, 2022
• First Submitted That Met QC Criteria: October 17, 2022
• First Posted (Actual): October 19, 2022

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 11, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: diphenhydramine; thermoregulation; anticholinergic; sweating
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Hypersensitivity, Immediate; Wounds and Injuries; Otorhinolaryngologic Diseases; Respiratory Hypersensitivity; Hypersensitivity; Nose Diseases; Body Temperature Changes; Heat Stress Disorders; Rhinitis; Rhinitis, Allergic; Hyperthermia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Antiemetics; Gastrointestinal Agents; Dermatologic Agents; Hypnotics and Sedatives; Anesthetics, Local; Anti-Allergic Agents; Sleep Aids, Pharmaceutical; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Antipruritics; Diphenhydramine; Promethazine
• Other Study ID Numbers: 2022509; 265937 (Other Identifier: Health Canada, Control Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No