Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623001158651
Ethics application status
Approved
Date submitted
17/10/2023
Date registered
8/11/2023
Date last updated
8/11/2023
Date data sharing statement initially provided
8/11/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
The influence of amitriptyline on human thermoregulation in young healthy adults
Scientific title
The influence of amitriptyline on critical thermal limits in young healthy adults
Secondary ID [1] 310803 0
Nil known
Universal Trial Number (UTN)
Trial acronym
AHT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Heat related thermal strain 331787 0
Heat related cardiovascular strain 331788 0
Heat related changes in thermal perceptions (i.e., comfort and sensation) 331789 0
Condition category
Condition code
Injuries and Accidents 328525 328525 0 0
Other injuries and accidents
Public Health 328526 328526 0 0
Other public health
Cardiovascular 328527 328527 0 0
Normal development and function of the cardiovascular system
Neurological 328627 328627 0 0
Studies of the normal brain and nervous system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 327214 0
Prevention
Intervention code [2] 327215 0
Early detection / Screening
Intervention code [3] 327216 0
Treatment: Drugs
Comparator / control treatment
Participants will be asked to complete a humidity ramp heat stress test 7 hours after oral ingestion of a single dose of identical placebo containing non-active microcrystalline cellulose. 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.

The study is a crossover trial with all participants carrying out an amitriptyline and a placebo control trial.
Control group
Placebo

Outcomes
Primary outcome [1] 336347 0
Critical relative humidity at which an inflection in rectal temperature is observed
Timepoint [1] 336347 0
The "critical" relative humidity is when an inflection in rectal temperature is observed during the ramp.
Secondary outcome [1] 427944 0
Critical relative humidity at which an inflection in heart rate is observed
Timepoint [1] 427944 0
The "critical" relative humidity is when an inflection in heart rate is observed during the ramp.
Secondary outcome [2] 427945 0
Change in rectal temperature
Timepoint [2] 427945 0
Change from minimum to maximum rectal temperature recorded during the heat stress test
Secondary outcome [3] 427946 0
Change in heart rate
Timepoint [3] 427946 0
Change from minimum to maximum heart rate recorded during the heat stress test
Secondary outcome [4] 427947 0
Perceptual rating of whole-body thermal sensation
Timepoint [4] 427947 0
At the end of baseline (30min) and every 16 min points, 38 to 118 min during the heat stress test.
Secondary outcome [5] 427948 0
Perceptual rating of whole-body thermal discomfort
Timepoint [5] 427948 0
At the end of baseline (30min) and every 16 min points, 38 to 118 min during the heat stress test.
Secondary outcome [6] 427949 0
Thirst perception
Timepoint [6] 427949 0
At the end of baseline (30min) and every 16 min points, 38 to 118 min during the heat stress test.
Secondary outcome [7] 427950 0
Whole body sweat rate/ loss
Timepoint [7] 427950 0
Body mass measurements will take place at the beginning and end of each heat stress test.
Secondary outcome [8] 427951 0
Activated sweat gland density
Timepoint [8] 427951 0
Sweat gland density will be measured at 94min and 118min during the heat stress test
Secondary outcome [9] 427952 0
Rectal Temperature
Timepoint [9] 427952 0
At end of baseline (30min) and every 16 min points, 38 to 118 min during the heat stress test
Secondary outcome [10] 427953 0
Heart Rate (absolute)
Timepoint [10] 427953 0
At end of baseline (30min) and every 16 min points, 38 to 118 min during the heat stress test
Secondary outcome [11] 427954 0
Rate pressure product
Timepoint [11] 427954 0
At end of baseline (30min) and every 16 min points, 38 to 118 min during the heat stress test
Secondary outcome [12] 427955 0
Skin blood flow
Timepoint [12] 427955 0
At end of baseline (30min) and every 16 min points, 38 to 118 min during the heat stress test
Secondary outcome [13] 427956 0
Local sweat rate
Timepoint [13] 427956 0
At end of baseline (30min) and every 16 min points, 38 to 118 min during the heat stress test

Eligibility
Key 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
Minimum age
18 Years
Maximum age
40 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation via a computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis
The relative humidity at which an inflection is observed and the change during the heat stress test, for both rectal temperature and heart rate, during PLA and AT administration will be performed using paired t-tests, as will HASGD at two time points (94 min and 138 min), and WBSL.

Differences in physiological responses (Trec, Tsk, BP, SkBF/CVC, and LSR) and perceptual measures (WBTS, WBTC, PTS) during PLA and AT administration throughout the heat stress test will be analysed using two-way repeated measures analysis of variance utilising the independent variables of treatment (2 levels: PLA, AT) and time (7 levels, end of baseline (30 min) every 16 min (38-118).

All values will be reported as the mean (±SD), and a the level for all statistical analyses will be set at 0.05.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
13/11/2023
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
12
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 315040 0
University
Name [1] 315040 0
The University of Sydney (Discretionary Research Account held by Dr. Ollie Jay)
Country [1] 315040 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
The University of Sydney Camperdown NSW 2006
Country
Australia
Secondary sponsor category [1] 317068 0
None
Name [1] 317068 0
Address [1] 317068 0
Country [1] 317068 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314001 0
The University of Sydney Human Research Ethics Committee
Ethics committee address [1] 314001 0
Research Integrity & Ethics Administration Research Portfolio Level 3, F23 Administration Building The University of Sydney, NSW, 2006
Ethics committee country [1] 314001 0
Australia
Date submitted for ethics approval [1] 314001 0
Approval date [1] 314001 0
25/07/2023
Ethics approval number [1] 314001 0
2022/449

Summary
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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 130082 0
Prof Ollie Jay
Address 130082 0
Susan Wakil Health Building, The University of Sydney, Western Ave, Camperdown NSW 2050
Country 130082 0
Australia
Phone 130082 0
+61 449116760
Fax 130082 0
Email 130082 0
ollie.jay@sydney.edu.au
Contact person for public queries
Name 130083 0
Prof Ollie Jay
Address 130083 0
Susan Wakil Health Building, The University of Sydney, Western Ave, Camperdown NSW 2050
Country 130083 0
Australia
Phone 130083 0
+61 449116760
Fax 130083 0
Email 130083 0
ollie.jay@sydney.edu.au
Contact person for scientific queries
Name 130084 0
Prof Ollie Jay
Address 130084 0
Susan Wakil Health Building, The University of Sydney, Western Ave, Camperdown NSW 2050
Country 130084 0
Australia
Phone 130084 0
+61 449116760
Fax 130084 0
Email 130084 0
ollie.jay@sydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual participant data underlying published results only.
When will data be available (start and end dates)?
Immediately following publication, no end date.
Available to whom?
Case-by-case basis at the discretion of the primary investigator.
Available for what types of analyses?
Meta-analysis.
How or where can data be obtained?
Access subject to approvals by the primary investigator with a requirement to sign a data access agreement. Email: ollie.jay@sydney.edu.au


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
20677Study protocol  ollie.jay@sydney.edu.au
20678Informed consent form  ollie.jay@sydney.edu.au



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.