None listed
Conditions
Brief summary
The influence of amitriptyline on critical thermal limits. Primary objective is to assess whether oral ingestion of amitriptyline influences critical thermal limits and thermal and cardiovascular strain during an acute heat stress. With a secondary outcome to assess whether oral ingestion of amitriptyline influences heat and thirst perception during an acute heat stress. Participants will be asked to complete a humidity ramp heat stress test 7 hours after oral ingestion of either i) 75 mg placebo (PLA) or, ii) 75 mg amitriptyline hydrochloride (AT). The heat stress test involves participants being exposed to 43°C, 20% relative humidity (RH) for 30 minutes before a stepwise increase in relative humidity occurs (4% every 8 min until 64% RH). The heating protocol is a standard methodological approach within the field of human thermoregulation. We anticipate that amitriptyline, an anticholinergic, may decrease sweat output, and as a result exacerbate the rectal temperature and heart rate response to a given heat stress.
Interventions
Participants will be asked to complete a humidity ramp heat stress test 7 hours after oral ingestion of a single dose of 75 mg amitriptyline hydrochloride or placebo. All participants will complete two trials, one with amitriptyline hydrochloride and one with placebo in a cross-over design with a wash-out period between treatments of at least 7 days. Ingestion of the drug/placebo will occur onsite and will be monitored by research staff.
The heat stress test involves participants being asked to
Participants will be asked to complete a humidity ramp heat stress test 7 hours after oral ingestion of a single dose of 75 mg amitriptyline hydrochloride or placebo. All participants will complete two trials, one with amitriptyline hydrochloride and one with placebo in a cross-over design with a wash-out period between treatments of at least 7 days. Ingestion of the drug/placebo will occur onsite and will be monitored by research staff. The heat stress test involves participants being asked to remain seated while exposed to 43°C, 20% relative humidity (RH) for 30 minutes before a stepwise increase in relative humidity occurs (4% every 8 min until 64% RH). The heating protocol is a standard methodological approach within the field of human thermoregulation. The total duration of the heat stress test is 118min. The heat stress test is carried out in a climate-controlled chamber at the research clinic and monitored by research staff.
Sponsors
The University of Sydney
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Prevention
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
1. Between the ages of 18-40 years 2. Able to understand the demands of the protocol, has had any questions answered and has voluntarily signed the participant consent form prior to any study procedures 3. In good health, a non-smoker, with no history of respiratory, metabolic, cardiovascular, blood pressure disease or diabetes and not currently taking any medication 4. Cleared for participation from licenced medical professional
Exclusion criteria
1. Determined at risk of bipolar disorder by the study physician, where screening includes detailed psychiatric history, family history of suicide, bipolar disorder and depression 2. Contraindications to rectal temperature including haemorrhoids, heterotopic ossification rectal bleeding or bleeding disorder, fissures or active infections, participants on anticoagulant therapy, and colitis 3. Current smoker 4. Pregnancy 5. History of seizures 6. Glaucoma 7. Cardiovascular disorder(s) 8. Endocrine disorder(s) 9. Hepatic/renal impairment(s) 10. Scheduled elective surgery (within the next 3 months) 11. Taking any regular medication(s), within five days of heat stress test. 12. Known hypersensitivity to amitriptyline
Outcome results
None listed