Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617000426381p
Ethics application status
Submitted, not yet approved
Date submitted
21/03/2017
Date registered
24/03/2017
Date last updated
24/03/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Can N-acetylcysteine (NAC) supplementation enhance altitude training in elite swimmers?
Scientific title
Can N-acetylcysteine (NAC) supplementation enhance the haematological response and reduce excessive exercise induced fatigue in elite swimmers during training camps at moderate altitudes?
Secondary ID [1] 291497 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Exercise performance 302567 0
exercise induced inflammation 302568 0
altitude induced illness 302570 0
Condition category
Condition code
Other 302095 302095 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Supplementation with N-acetylcysteine (NAC) in a randomised, double-blind, placebo controlled study to assess the effects of supplementation on erythropoiesis, exercise-induced inflammation and performance during altitude training in athletes.
N-acetylcysteine (NAC) will be administered orally in tablet form, 1200 mg per day, daily for 2.5 weeks
Randomised parallel groups matched pair design. This study design is optimal as it allows for comparison of the intervention effects between closely matched participants while avoiding the impracticality of using two within-subjects factors, i.e. long washout period required between interventions. Elite swimmers (n = 20) will receive either NAC (1200 mg/d) (n=13) or a placebo (n=7) supplement 4 days prior to departure and for the initial 2 wk of a 4 wk training camp (funded by Swimming Australia) in Thredbo, AUS (elevation 1300 m). Select athletes (random allocation) in the supplementation group (n=7) will also spend 10-12 hours per day (7-9 hours nightly, 2-3 hours during the day) exposure to normobaric hypoxia (simulated altitude 3000 m, 17% oxygen) via the use of hypoxic tents which will occur during the entire 4 week altitude training camp. Researchers will be present in-person on the training camp to encourage compliance with supplementation and other experimental procedures. Performance will be assessed via a 2km swim time trial and an incremental swim step test pre, post and 1 week post the altitude training camp. Baseline measures for blood iron status (serum iron, ferritin, transferrin saturation, iron incorporation) will be taken to determine suitability (see exclusion criteria under eligibility) for iron supplementation at altitude (prescribed daily for 5 weeks, 1 week prior to altitude training and entire 4 weeks altitude training, Ferro-Grad C, Abbott Laboratories, Australia - 100 mg elemental iron once daily with dinner, oral tablet supplement)), and participants will be excluded from taking any other antioxidant supplements. Venous blood samples will be taken at baseline (pre-departure to altitude), after 36 h and 2 wk at altitude, and immediately prior return to sealevel to determine haematological (EPO, reticulocytes) oxidative (GSH:GSSG ratio, F2-isoprostane) and adaptive (NFKB) responses to altitude training and supplementation. Haemoglobin mass will be assessed via CO rebreathing pre and post altitude training. Throughout the investigation, athletes will complete a daily wellness diary to assess the impact of supplementation on athlete health, incidence of illness and tolerance to training. Training load will be individualised to each athlete by personal coaches, and monitored using session RPE throughout the altitude intervention, and 4 wk prior. Participants will be randomly matched in pairs according to baseline; ferritin status, training load, gender and performance
Intervention code [1] 297567 0
Treatment: Drugs
Comparator / control treatment
Placebo (sucrose), oral administration in tablet form, identical in size and appearance to NAC treatment
Control group
Placebo

Outcomes
Primary outcome [1] 301537 0
Changes in markers of erythropoiesis (Hypoxic - inducible factor 1alpha, EPO) will be assessed through venous blood samples at various timepoints.
Timepoint [1] 301537 0
At baseline (prior to supplementation and altitude exposure), after 36 hours at altitude, after 2 weeks altitude, at the conclusion of altitude (4 weeks)
Primary outcome [2] 301538 0
Changes in haemoglobin mass
Capillary blood samples will be taken for measurement of haemoglobin mass via modified carbon monoxide rebreathing method
Timepoint [2] 301538 0
At baseline (following 4 days NAC supplementation at the commencement [day 1] of altitude exposure), and post altitude exposure (4 weeks)
Primary outcome [3] 301540 0
Changes in performance
Performance testing will consist of a 2km swim time trial and an incremental swim step test
Timepoint [3] 301540 0
pre, post and 1 week post the altitude training camp.
Secondary outcome [1] 332961 0
Athlete training status
Customised training questionnaire utilising the session rating of perceived exertion (RPE) method of training quantification. Briefly, for each training session, participants provide the duration in minutes, distance completed in kilometres (blank if strength training/cross training) and an RPE score (0-10) with 0 being no exertion and 10 being maximal exertion. Session load is calculated by multiplying duration and RPE. As per Foster et al., 2001, A new approach to monitoring exercise training, Journal of Strength and Conditioning Research, 15, 109-115
Timepoint [1] 332961 0
Daily during study period (from 4 weeks prior to commencement of supplementation until end of 4 week altitude exposure).
Secondary outcome [2] 333011 0
Athlete health and wellbeing
Customised health and wellness questionnaire
Briefly, participants are asked to rate on a 1-10 Likert scale (1 not at all/poor/minimal, 10 extremely/excellent) perceptions of sleep quality, body soreness, fatigue, general health, mood, mental readiness to train, physical readiness to train. Additionally, participants will be ask yes/no whether they are sick, and if yes, to list any symptoms e.g. headache, upper respiratory, congestion etc.
Timepoint [2] 333011 0
Daily during study period (from 4 weeks prior to commencement of supplementation until end of 4 week altitude exposure).
Secondary outcome [3] 333012 0
Changes in markers of oxidative stress (GSH:GSSG ratio) will be assessed through venous blood samples at various timepoints.
Primary outcome
Timepoint [3] 333012 0
At baseline (prior to supplementation and altitude exposure), after 36 hours at altitude, after 2 weeks altitude, at the conclusion of altitude (4 weeks)
Secondary outcome [4] 333013 0
Changes in markers of cellular adaptation to endurance training (nuclear factor kappa B) will be assessed through venous blood samples at various timepoints.
Primary outcome
Timepoint [4] 333013 0
At baseline (prior to supplementation and altitude exposure), after 36 hours at altitude, after 2 weeks altitude, at the conclusion of altitude (4 weeks)

Eligibility
Key inclusion criteria
For inclusion in the investigation, participants must fulfil the below criteria:
Sex: Male and female
Age range: 18 to 40 y
Disease status: Healthy individuals
Elite swimmers with high level of physical fitness (VO2max above 55 ml/kg/min)
Completed 10-15 hrs of training per week for at least 2 years
Willingness to give written and oral informed consent.
Willingness to participate to and comply with the study
Minimum age
18 Years
Maximum age
40 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Participants will be excluded from participantion based on the below criteria:
Regular NAC supplementation use for the previous 6 months
Illness or injury which may be exacerbated through participation in the study
Exposure to a hypoxic stimulus in the previous 3 months
Inconsistent pretesting diet and exercise
Participants with low ferritin levels (30-100ug/L) prior to the commencement of the study will be required to take daily oral iron supplement (Ferrograd C: 100 mg elemental iron) during the course of the study.
Women lactating, pregnant or of childbearing potential who are not willing to avoid becoming pregnant during the study.
Patients with a history of a psychological illness or condition such as to interfere with the patient's ability to understand the requirements of the study.
Patients with a haematological disease that is likely to interfere with the evaluation of the patient's safety and of the study outcome.
The following medication(s) can have interactive effects, may confound the findings of the investigation and may interfere with the patient's ability to meet the study requirements; they cannot be administered during the clinical study:
Any antioxidant vitamins and mineral supplement
Any substance or method included in the World Anti-Doping Association List of Prohibited Substances and Methods. Unless the participant has a Therapeutic USE Exemption for the substance /method from the Australian Sports Anti-Doping Authority

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation via computer - participants pair matched and randomly allocated based on age, gender, training load, performance characteristics and baseline ferritin stores
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
Parallel
Other design features
parallel groups trial with randomised allocation
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
General Linear Mixed Model. Changes from baseline in performance tests (2km time trial, swimming step test), haematological (haemoglobin mass, reticulocytes, EPO), oxidative (GSSG:GSH ratio, F2-isoprostane) and exercise adaptation (NFKB) markers will be considered as dependent variables, with gender, supplementation condition, training load and time entered as fixed effects and participants as random effects.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/08/2017
Actual
Date of last participant enrolment
Anticipated
31/08/2017
Actual
Date of last data collection
Anticipated
31/10/2017
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,VIC

Funding & Sponsors
Funding source category [1] 295980 0
Government body
Name [1] 295980 0
Australian Institute of Sport
Country [1] 295980 0
Australia
Funding source category [2] 295983 0
Other Collaborative groups
Name [2] 295983 0
Swimming Australia
Country [2] 295983 0
Australia
Funding source category [3] 295984 0
Government body
Name [3] 295984 0
NSW Institute of Sport
Country [3] 295984 0
Australia
Funding source category [4] 295985 0
University
Name [4] 295985 0
University Technology Sydney
Country [4] 295985 0
Australia
Funding source category [5] 295986 0
University
Name [5] 295986 0
Australian Catholic University
Country [5] 295986 0
Australia
Primary sponsor type
Government body
Name
Australian Institute of Sport
Address
Leverrier St, Bruce ACT 2617
Country
Australia
Secondary sponsor category [1] 294869 0
Government body
Name [1] 294869 0
NSW Institute of Sport
Address [1] 294869 0
1/6 Figtree Dr, Sydney Olympic Park NSW 2127
Country [1] 294869 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 297246 0
UTS Human Research Ethics committee
Ethics committee address [1] 297246 0
Ethics committee country [1] 297246 0
Australia
Date submitted for ethics approval [1] 297246 0
22/02/2017
Approval date [1] 297246 0
Ethics approval number [1] 297246 0

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

Contacts
Principal investigator
Name 73450 0
Dr Katie M Slattery
Address 73450 0
UTS Sport and Exercise Science, Moore Park precinct, PO Box 123 Broadway NSW 2007
Country 73450 0
Australia
Phone 73450 0
+61 412 352 843
Fax 73450 0
Email 73450 0
[email protected]
Contact person for public queries
Name 73451 0
Avish P Sharma
Address 73451 0
Physiology, Australian Institute of Sport, Leverrier Cres Bruce, ACT, 2617
Country 73451 0
Australia
Phone 73451 0
+61432975939
Fax 73451 0
Email 73451 0
[email protected]
Contact person for scientific queries
Name 73452 0
Katie M Slattery
Address 73452 0
UTS Sport and Exercise Science, Moore Park precinct, PO Box 123 Broadway NSW 2007
Country 73452 0
Australia
Phone 73452 0
+61412352843
Fax 73452 0
Email 73452 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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