Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000988853p
Ethics application status
Submitted, not yet approved
Date submitted
23/06/2021
Date registered
28/07/2021
Date last updated
28/07/2021
Date data sharing statement initially provided
28/07/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Performance and metabolic effects following a single course of antibiotic treatments in healthy individuals
Scientific title
Performance and metabolic effects following a single course of cephalexin in healthy individuals
Secondary ID [1] 304549 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Athletic Performance 322424 0
Condition category
Condition code
Metabolic and Endocrine 320077 320077 0 0
Normal metabolism and endocrine development and function

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
1.1 Overview
The study will adopt a single-arm trial design, using pre- and post-outcomes to test the hypotheses. Eligibility and health screening questionnaire will be conducted by phone. Participants will attend three laboratory sessions at Murdoch University physiology laboratory; a familiarisation session with VO2peak assessment, and two experimental sessions with no less than 5 days separating sessions. Familiarisation session will used to familiarise participants with the equipment and the time-trial adopted within the study and attain lactate values of corresponding power outputs for experimental sessions.

1.2 Procedures

1.2.1 Familiarisation session and VO2peak
Participants will attend following an overnight fast >10hrs to best replicate testing conditions. Following collection of height and body mass, participants will complete a maximal aerobic performance test (VO2max), using an electromagnetically braked Velotron cycle ergometer (Racermate, USA). Expired ventilation will be collected continuously using a metabolic cart (TrueOne 2400, ParvoMedics, USA). All participants will start at a workload of 50W which will be increased by 35 W every two minutes. Finger-stick lactate will be collected in the final 30 seconds of each stage. Once RER has reached 1.0, workload (35W) will be increased every minute until volitional exhaustion. From this a work output corresponding to a blood lactate of 3mM will be calculated for use in the constant-work component in the experimental sessions. Participants will then be familiarised with the time-trial, which will begin ~20 minutes after completion of the VO2max test. The time-trial will be based on completion of a caloric goal, which will be standardised at 400 Calories for all participants. Participants are able to self-select their cadence as well as gearing and will be able to adjust these throughout the time-trial. Participants will be able to consume water ad libitum before and during the time trial.

1.2.2 Experimental Trials
Both experimental trials will be conducted in the morning following an overnight fast >10hrs. Participants will be asked to maintain a 72-hour food and exercise diary prior to the first experimental trial. Normal exercise may be continued leading up to the first experimental trial and participants should best replicate the diary conditions leading up to the second experimental trial. Heavy training in the 24 hour period immediately prior to trials will be discouraged.
Each trial consists of a 60 minute steady state (fixed power) cycling at power output corresponding to 3mM of lactate on a Velotron cycle ergometer (Racermate, USA), followed immediately by a time trial for 400 calories. Gas exchange data will be collected using a metabolic cart during the fixed power cycling (TrueOne 2400, ParvoMedics, USA), with heart rate date collected using a heart rate monitor (Garmin, USA). Ratings of perceived exertion (RPE) will be collected using the 6-20 Borg scale (10) and measured every 15 min during fixed power exercise, and every 5 min during the time trial and 5 minutes post completion. During the time-trial, only heart rate and RPE will be collected at each 100 Calorie point.

Following experimental trial one, participants will be asked to commence a five-day course of oral Cephalexin 500mg, with dosing as 06:00, 12:00, 18:00, and 20:00. First dose should commence at 12:00 on day one, with the final dose taken at 06:00 on the day of experimental trial two (Day 6). Participants will be monitored in the laboratory for one hour post administration of the first dose to assess for serious side effects (11). Adherence to the Cephalexin dosing will be monitored through a diary and participants will receive two text messages during the 5-day course as a reminder. At the completion of experimental trial two, participants will be asked regarding compliance and report whether any doses were missed.

1.2.3 Blood sampling and analysis
Blood sampling in each trial will occur from a cubital fossa vein. A 20 gauge peripheral venous cannula will be placed using sterile technique. 4ml of blood will be collected via using lithium heparin vacutainer tubes. The cannula will be flushed with 10ml 0.9% saline after each sample is taken. 4mL of blood will be taken and discarded prior to collection of sample two and three to ensure no saline remains in the cannula. Samples will be taken prior to commencement of activity, after the fixed output session, and immediately after the completion of the time trial.

Testing and sampling will be completed by Dr Ewan Smith, medical doctor 8 years. Laboratory supervision by Associate Professor in Exercise Physiology Timothy Fairchild. Ethics approval is has been applied for with the Murdoch University Human Research Ethics Committee.
Intervention code [1] 320898 0
Treatment: Drugs
Comparator / control treatment
No Control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 327952 0
A change in time trial performance from the first time trial as assessed by time to completion of a 400 calorie time trial on an electronically braked cycle ergometer.
Timepoint [1] 327952 0
At time of second trial (Day 6)
Secondary outcome [1] 397079 0
Changes to perceived exertion using Borg scale at submaximal power outputs.
Timepoint [1] 397079 0
At time of second trial (Day 6)
Secondary outcome [2] 397080 0
Changes in serum long chain serum acylcarnitines as measured by analysis of plasma using a mass spectrometer.
Timepoint [2] 397080 0
At time of second trial (Day 6)
Secondary outcome [3] 397122 0
Changes respiratory exchange ratio during submaximal cycling effort as assessed by continuous gas collection with a metabolic cart.
Timepoint [3] 397122 0
At time of second trial (Day 6)
Secondary outcome [4] 397123 0
Heart rate during submaximal power output assessed using a heart rate monitor
Timepoint [4] 397123 0
At time of second trial (Day 6)
Secondary outcome [5] 398113 0
Changes to perceived exertion using Borg scale at maximal power outputs.
Timepoint [5] 398113 0
Time of second time trial (day 6)
Secondary outcome [6] 398114 0
Heart rate maximal power output assessed using a heart rate monitor
Timepoint [6] 398114 0
At time of second trial (day 6)
Secondary outcome [7] 398115 0
Changes in serum 5-methoxy-3-indoleacetic acid as measured by analysis of plasma using a mass spectrometer.
Timepoint [7] 398115 0
At time of second trial (Day 6)

Eligibility
Key inclusion criteria
Sixteen recreationally trained cyclists (cycling a minimum 200 km/week) ages 18-40 will be recruited to participate in the study.
Minimum age
18 Years
Maximum age
40 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
The participants will be screened via email and telephone using the Exercise and Sports Science Australia (ESSA) risk stratification questionnaire. Further exclusion criteria include cephalosporin or penicillin allergy, hypo/hyperthyroidism, type 1 or 2 diabetes, and chronic renal failure.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
Using data from a previously published 16.1 km time-trial (1626±72 sec) in club level cyclists (1), 14 participants were required to detect a 2.5% improvement in the primary outcome of the study, namely time-trial performance (two-tailed; a=0.05; power=0.8). To allow for drop-out and missing data, a total of sixteen participants will be recruited.

A paired sample t-test will be used to assess differences (p<0.05; IBM SPSS Statistics 22) in the time-trial performance (primary outcome). Absolute differences (p<0.05) between the trials will be presented with 95% confidence intervals (CI) and effect size estimates will be calculated using Hedge’s g (unbiased).

For measures of RER, HR, and RPE (which are collected multiple times throughout each experimental phase), random intercept, linear mixed models will be used to examine the effects of condition (Pre vs Post) and time (repeated measure within trial) on each outcome measure. Condition and time will be modelled as fixed effects. Both the condition by time interaction as well as main effects of condition and time will be explored using least significance difference (LSD).

Metabolite data will be combined into a single data matrix. Data will be scaled and visualised using principal component analysis (PCA) and hierarchical cluster analysis (HCA). For each identified metabolite, the null hypothesis that there is no difference in population means across time points will be tested using repeated measures analysis of variance. Correction for multiple comparisons will be performed and both p values and corrected q values reported.. All identified metabolites will then be combined into a multivariate model using PCA and bootstrap resampling used to determine metabolite significance (Matlab scripting language v.R2017a).


1. Black MI, Durant J, Jones AM, Vanhatalo A. Critical power derived from a 3-min all-out test predicts 16.1-km road time-trial performance. European Journal of Sport Science. 2014;14(3):217-23.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
23/08/2021
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
16
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 308918 0
University
Name [1] 308918 0
Murdoch University
Country [1] 308918 0
Australia
Primary sponsor type
University
Name
Murdoch University
Address
90 South St, Murdoch WA 6150
Country
Australia
Secondary sponsor category [1] 309840 0
None
Name [1] 309840 0
Address [1] 309840 0
Country [1] 309840 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 308810 0
Human Research Ethics Committee Murdoch University
Ethics committee address [1] 308810 0
Ethics committee country [1] 308810 0
Australia
Date submitted for ethics approval [1] 308810 0
19/04/2021
Approval date [1] 308810 0
Ethics approval number [1] 308810 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 111970 0
Dr Ewan Smith
Address 111970 0
Murdoch University
90 South St,
Murdoch WA 6150
Country 111970 0
Australia
Phone 111970 0
+61 08 9360 2959
Fax 111970 0
Email 111970 0
[email protected]
Contact person for public queries
Name 111971 0
Ewan Smith
Address 111971 0
Murdoch University
90 South St,
Murdoch WA 6150
Country 111971 0
Australia
Phone 111971 0
+61 08 9360 2959
Fax 111971 0
Email 111971 0
[email protected]
Contact person for scientific queries
Name 111972 0
Ewan Smith
Address 111972 0
Murdoch University
90 South St,
Murdoch WA 6150
Country 111972 0
Australia
Phone 111972 0
+61 08 9360 2959
Fax 111972 0
Email 111972 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, supplementary data)
When will data be available (start and end dates)?
Beginning 3 months and ending 5 years following article publication.
Available to whom?
Researchers who provide a sound methodological proposal.
Available for what types of analyses?
meta-analyses
How or where can data be obtained?
Proposals should be directed to [email protected].


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
12177Ethical approval  [email protected]



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

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