Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617000427370p
Ethics application status
Submitted, not yet approved
Date submitted
21/03/2017
Date registered
24/03/2017
Date last updated
11/04/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Can N-acetylcysteine (NAC) supplementation enhance altitude training in elite runners?
Scientific title
Can N-acetylcysteine supplementation enhance the haematological response and reduce excessive exercise induced fatigue in elite runners during training camps at moderate altitudes?
Secondary ID [1] 291495 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Exercise Performance 302561 0
Exercise induced inflammation 302562 0
Altitude induced illness 302564 0
Condition category
Condition code
Other 302093 302093 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 18 days
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 middle distance runners (n = 18) will receive either NAC (1200 mg/d) or a placebo supplement 4 days prior to departure and for the initial 2 wk of a 4 wk training camp (funded by Athletics Australia) in Flagstaff, USA (elevation 2100 m). Performance will be assessed via competitions within the 3 wk preceding and following the 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 (Ferro-Grad C, Abbott Laboratories, Australia - 100 mg elemental iron once daily with dinner for 5 weeks, [1 week pre altitude, 4 weeks at altitude], oral tablet supplement), and participants will be excluded from taking any other antioxidant supplements. Researchers will be present in-person on the training camp to encourage compliance with supplementation and other experimental procedures. 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 sea-level to determine haematological (erythropoietin - EPO, reticulocytes) oxidative (GSH:GSSG ratio, F2-isoprostane) and adaptive (nuclear factor kappa B - 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 GPS watches (Forerunner, Garmin, USA)/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. At the same time-points as venous blood samples, participants will complete a 6 minute running test on a motorised treadmill at a submaximal intensity - 2 x 3 minute stages at 13 and 15 kmph for females and 14 and 16 kmph for males. Heart rate and and subjective rating of perceived exertion will be measured during these trials. This will be included to measure the effect of NAC supplementation on tolerance to exercise at altitude.
Intervention code [1] 297563 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] 301534 0
Changes in markers of erythropoiesis (Hypoxic - inducible factor 1alpha, EPO) will be assessed through venous blood samples at various timepoints.
Timepoint [1] 301534 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] 301535 0
Changes in haemoglobin mass
Capillary blood samples will be taken for measurement of haemoglobin mass via modified carbon monoxide rebreathing method
Timepoint [2] 301535 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] 301536 0
Changes in middle distance race performance (i.e. 800/1500/3000m steeplechase/5000 m running race time) as recorded at competition
Timepoint [3] 301536 0
At baseline (within 4 weeks prior to supplementation and altitude exposure), and within 2 weeks post 4 weeks altitude exposure
Secondary outcome [1] 332948 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] 332948 0
Daily during study period (from 4 weeks prior to commencement of supplementation until end of 4 week altitude exposure).
Secondary outcome [2] 333003 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] 333003 0
Daily during study period (from 4 weeks prior to commencement of supplementation until end of 4 week altitude exposure).
Secondary outcome [3] 333004 0
Changes in markers of oxidative stress (GSH:GSSG ratio) will be assessed through venous blood samples at various timepoints.
Primary outcome
Timepoint [3] 333004 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] 333005 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] 333005 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 [5] 333709 0
Tolerance to exercise at altitude - 6 minute submaximal running test - Heart rate and rating of perceived exertion responses
Timepoint [5] 333709 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 ful l the below criteria:
Sex: Male and female
Age range: 18 to 40 y
Disease status: Healthy individuals
Elite middle distance runners with a high level of physical fitness (VO2max above 55 ml/kg/min)
Completed 10 to 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 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 competition performance, 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
17/04/2017
Actual
Date of last participant enrolment
Anticipated
15/04/2017
Actual
Date of last data collection
Anticipated
20/06/2017
Actual
Sample size
Target
18
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,TAS,VIC

Funding & Sponsors
Funding source category [1] 295974 0
Government body
Name [1] 295974 0
Australian Institute of Sport
Country [1] 295974 0
Australia
Funding source category [2] 295976 0
Other Collaborative groups
Name [2] 295976 0
Athletics Australia
Country [2] 295976 0
Australia
Funding source category [3] 295977 0
Government body
Name [3] 295977 0
NSW Institute of Sport
Country [3] 295977 0
Australia
Funding source category [4] 295978 0
University
Name [4] 295978 0
University Technology Sydney
Country [4] 295978 0
Australia
Funding source category [5] 295979 0
University
Name [5] 295979 0
Australian Catholic University
Country [5] 295979 0
Australia
Primary sponsor type
Government body
Name
Australian Institute of Sport
Address
Leverrier St, Bruce ACT 2617
Country
Australia
Secondary sponsor category [1] 294867 0
Government body
Name [1] 294867 0
NSW Institute of Sport
Address [1] 294867 0
1/6 Figtree Dr, Sydney Olympic Park NSW 2127
Country [1] 294867 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 297244 0
UTS Human Research Ethics Committee
Ethics committee address [1] 297244 0
Ethics committee country [1] 297244 0
Australia
Date submitted for ethics approval [1] 297244 0
22/02/2017
Approval date [1] 297244 0
Ethics approval number [1] 297244 0

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

Contacts
Principal investigator
Name 73442 0
Dr Katie M Slattery
Address 73442 0
UTS Sport and Exercise Science, Moore Park precinct, PO Box 123 Broadway NSW 2007
Country 73442 0
Australia
Phone 73442 0
+61 412 352 843
Fax 73442 0
Email 73442 0
[email protected]
Contact person for public queries
Name 73443 0
Avish P Sharma
Address 73443 0
Physiology, Australian Institute of Sport, Leverrier Cres Bruce, ACT, 2617
Country 73443 0
Australia
Phone 73443 0
+61432975939
Fax 73443 0
Email 73443 0
[email protected]
Contact person for scientific queries
Name 73444 0
Katie M Slattery
Address 73444 0
UTS Sport and Exercise Science, Moore Park precinct, PO Box 123 Broadway NSW 2007
Country 73444 0
Australia
Phone 73444 0
+61412352843
Fax 73444 0
Email 73444 0
[email protected]

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What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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