Heat IllnessPhase 4NCT06217367
Over-the-Counter Antihistamines & Heat Stress
A Phase 4 study testing 50 mg Diphenhydramine, 10 mg Loratadine and 5 mg Desloratadine in people with Heat Illness and Allergic Rhinitis, run by Lakehead University at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 19 to 39 yearsHealthy volunteers can take part
- Conditions the study is for
- Heat Illness, Allergic Rhinitis, Heat Injury
- What is being tested?
- 50 mg Diphenhydramine, 10 mg Loratadine and 5 mg Desloratadine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteCanada
- Study dates
- 5 Dec 2023to Jun 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 39 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male or Female between ages 19 and 39 years
- Fully vaccinated against COVID-19
- Able to provide informed consent
- Body-mass index under 30
Who cannot join
- 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 locations and contacts
1 site in 1 country.
Canada1 site, 1 recruiting
- Recruiting
Lakehead University C.J Sanders Fieldhouse
Thunder Bay, Ontario, P7B5E1
Nicholas Ravanelli, PhD, 6132630361, nravanel@lakeheadu.ca
Nicholas Ravanelli, PhD
About this study
Official title: Do Common Over-the-counter Antihistamine Medications Modify Thermoregulatory Responses During Passive Heat Stress?
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.
- Being tested
- 50 mg Diphenhydramine, 10 mg Loratadine, 5 mg Desloratadine, Placebo (Sugar Pill)
- 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
- Medical subject headings
- Heat Stress Disorders, Rhinitis, Allergic, Wounds and Injuries, Drug Hypersensitivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
50 mg DiphenhydramineDrug
Also called Benadryl®
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.
10 mg LoratadineDrug
Also called Claritin®
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.
5 mg DesloratadineDrug
Also called Aerius®
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.
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.
| Study group | Role | What they receive |
|---|---|---|
| 50 mg Diphenhydramine | Experimental | Not described Receives: Drug: 50 mg Diphenhydramine |
| 10 mg Loratadine | Experimental | Not described Receives: Drug: 10 mg Loratadine |
| 5 mg Desloratadine | Experimental | Not described Receives: Drug: 5 mg Desloratadine |
| Placebo (Sugar pill) | Placebo comparator | Not described Receives: Other: Placebo (Sugar Pill) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Whole-Body Sweat Losses
Difference in participants' pre/post body mass
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Self-assessments of thermal sensation using a 7-point analog scale where -3 is "Cold" and +3 is "Hot".
Measured: 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
Self-assessments of thermal comfort using four-point analog scale where 1 is "Not uncomfortable" and 4 is "Very uncomfortable"
Measured: 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
Indexed with digital Stroop test
Measured: 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
Measured using Stanford Sleepiness Scale (min: 1, max: 7 (more fatigued))
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2024
- Study start5 Dec 2023
- Primary completionJun 2024 (estimated)
- Study completionJun 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heat IllnessStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- 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.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 16 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Lakehead University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nicholas Ravanelli, Lakehead University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06217367
- Sponsor's protocol ID
- 100241
- Other IDs
- 273752
- Status last verified
- Jan 2024
- First submitted
- 8 Nov 2023
- Last updated
- 22 Jan 2024
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Do Common Over-the-counter Antihistamine Medications Modify Thermoregulatory Responses During Passive Heat Stress?
- ClinicalTrials.gov ID
- NCT06217367
- Acronym / sponsor ID
- 100241
- Keywords
- H1 antihistamine, Sweating, Heat stress, Thermoregulation, M3 Muscarinic receptors, H1 receptor antagonism, M3 Muscarinic receptor blockade, Heat Illness/Injury
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 16 participants (estimated)
- Lead sponsor
- Lakehead UniversityUniversity, hospital or other
- Study start
- 5 Dec 2023 (actual)
- Primary completion
- Jun 2024 (estimated)
- Study completion
- Jun 2024 (estimated)
- First posted
- 22 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
- 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.
| Arm | Type | Receives |
|---|---|---|
| 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) |
Who may qualify
- Ages
- 19 to 39 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Male or Female between ages 19 and 39 years
- Fully vaccinated against COVID-19
- Able to provide informed consent
- Body-mass index under 30
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 50 mg DiphenhydramineAlso: Benadryl®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. | Drug | 50 mg Diphenhydramine |
| 10 mg LoratadineAlso: Claritin®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. | Drug | 10 mg Loratadine |
| 5 mg DesloratadineAlso: Aerius®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. | Drug | 5 mg Desloratadine |
| Placebo (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. | Other | Placebo (Sugar pill) |
Primary outcome
Whole-Body Sweat Losses
Time frame: For each study arm (all completed within 4 months), measurements taken immediately before heating protocol & immediately following the heating protocol
Difference in participants' pre/post body mass
Skin Blood Flow
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
Measured using laser-doppler skin blood blow sensor affixed to forearm
Heart Rate
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
Measured using electrocardiogram
Mean Arterial Pressure
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
Measured using brachial blood pressure cuff
Local Sweat Rate
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
Measured using ventilated sweat capsules affixed to forearm and chest
4 secondary outcomes
Thermal Sensation
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
Thermal Comfort
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
Mental Acuity
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
Sleepiness/Fatigue level
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing 50 mg Diphenhydramine, 10 mg Loratadine and 5 mg Desloratadine in people with Heat Illness and Allergic Rhinitis, run by Lakehead University at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Nicholas Ravanelli, PhD (6132630361, nravanel@lakeheadu.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Whole-Body Sweat Losses (time frame: For each study arm (all completed within 4 months), measurements taken immediately before heating protocol & immediately following the heating protocol). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2024.