Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000135112
Ethics application status
Approved
Date submitted
21/01/2019
Date registered
30/01/2019
Date last updated
9/04/2019
Date data sharing statement initially provided
30/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Sex differences in exercise induced gastrointestinal damage amongst recreational athletes: A Pilot Study
Scientific title
Sex dimorphism in exercise induced gastrointestinal damage amongst recreational athletes: A Pilot Study
Secondary ID [1] 297148 0
Nil known
Universal Trial Number (UTN)
U1111-1227-1618
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Intestinal damage 311178 0
Menstruation 311260 0
Condition category
Condition code
Oral and Gastrointestinal 309799 309799 0 0
Normal oral and gastrointestinal development and function
Reproductive Health and Childbirth 309883 309883 0 0
Menstruation and menopause

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention 1: Exercise. We will be exploring the effect of exercise (the intervention) on gut damage during the menstrual cycle.

There will be three groups of participants recruited:
1. Males
2. Females with a regular, natural menstrual cycle
3. Females with a regular cycle using a hormonal contraceptive

Participants will run on a treadmill in a climate controlled room (~21 deg c, 40% relative humidity) at the University of Tasmania Newnham Campus.
There will be 3 x 1 hour sessions for all participants. They will run at a continuous effort of 70% of VO2max.
Sessions for males will be 1 x per week on the same day at the same time each week.
Sessions for females will be in accordance with their menstrual cycle, but approximately on days 1-4 (early follicular), day 11-14 (late follicular) and day 21-25 (mid luteal). Each trial for females will be at the same time of day.
Only one participant will be tested at a time.

Intervention 2: Sugar solution. Participants will ingest a sugar solution that will be used to identify gut permeability during exercise (intervention 1).
5 g lactulose and 5 g L-rhamnose will be dissolved in 150 ml tap water and ingested by the participant 5 minutes prior to the start of each exercise trial.

The interventions will be delivered by the research team, all of whom are university researchers and exercise professionals.
Intervention code [1] 313409 0
Lifestyle
Comparator / control treatment
Comparisons are being made between three different participant groups: females with a natural menstrual cycle, females on hormonal contraceptives and males.

The participants will act as their own controls, but males also act as a control since they do not have a menstrual cycle.
Control group
Active

Outcomes
Primary outcome [1] 318762 0
A difference in post-exercise plasma I-FABP concentration at the different timepoints and betwen males and females

Plasma I-FABP concentration will be analysed via ELISA
Timepoint [1] 318762 0
Pre- and Post exercise blood samples will be taken at every trial for analysis.
Pre-exercise blood samples will be taken within 10 minutes prior to the sugar intervention and 15 minutes prior to the exercise intervention
Post-exercise samples will be taken immediately upon cessation of the exercise trial (and therefore approx 65 minutes post-sugar intervention)
Timepoints of trials are:
Males: 1 x per week for three weeks on the same day at the same time each week.
Females: in accordance with their menstrual cycle, but approximately on days 1-4 (early follicular), day 11-14 (late follicular) and day 21-25 (mid luteal). Each trial for females will be at the same time of day.

Because the groups are being compared throughout the phases of the menstrual cycle, the timepoints are pre- and post- exercise for 3 trials in accordance with the schedule noted above
Secondary outcome [1] 365942 0
Indications of intestinal permeability as defined by the lactulose/rhamnose ratio via a plasma assay
Timepoint [1] 365942 0
Pre- and Post exercise blood samples will be taken at every trial for analysis.
Pre-exercise blood samples will be taken within 10 minutes prior to the sugar intervention and 15 minutes prior to the exercise intervention
Post-exercise samples will be taken immediately upon cessation of the exercise trial (and therefore approx 65 minutes post-sugar intervention)
Timepoints of trials are:
Males: 1 x per week for 3 weeks on the same day at the same time each week.
Females: in accordance with their menstrual cycle, but approximately on days 1-4 (early follicular), day 11-14 (late follicular) and day 21-25 (mid luteal). Each trial for females will be at the same time of day.
Secondary outcome [2] 366151 0
Oestrogen concentrations will be analysed using serum ELISA to verify the menstrual cycle phase
Timepoint [2] 366151 0
Pre- and Post exercise blood samples will be taken at every trial for analysis.
Pre-exercise blood samples will be taken within 10 minutes prior to the sugar intervention and 15 minutes prior to the sugar intervention
Post-exercise samples will be taken immediately upon cessation of the exercise trial (and therefore approx 65 minutes post-sugar intervention)
Timepoints of trials are:
Males: 1 x per week on the same day at the same time each week.
Females: in accordance with their menstrual cycle, but approximately on days 1-4 (early follicular), day 11-14 (late follicular) and day 21-25 (mid luteal). Each trial for females will be at the same time of day.
Secondary outcome [3] 366257 0
Progesterone concentrations will be analysed via serum ELISA to verify menstrual cycle phase
Timepoint [3] 366257 0
Pre- and Post exercise blood samples will be taken at every trial for analysis.
Pre-exercise blood samples will be taken within 10 minutes prior to the sugar intervention and 15 minutes prior to the sugar intervention
Post-exercise samples will be taken immediately upon cessation of the exercise trial (and therefore approx 65 minutes post-sugar intervention)
Timepoints of trials are:
Males: 1 x per week for three weeks on the same day at the same time each week
Females: in accordance with their menstrual cycle, but approximately on days 1-4 (early follicular), day 11-14 (late follicular) and day 21-25 (mid luteal). Each trial for females will be at the same time of day.

Eligibility
Key inclusion criteria
• Trained (recreational athletes), currently training a minimum of 5 hours a week (female and male)
• Self-reported regular menstrual cycles with no history of dysfunction (females only)
• BMI within healthy range (female and male)
• Able to run on a treadmill for an hour (female and male)
• Natural cycle: have not taken hormonal contraceptives for at least 6 months and self-reported menstrual cycle is regular (24-35 days) (females only)
OR
• hormonal contraceptive: : have consistently taken a hormonal contraceptive for at least 6 months (females only)
Minimum age
18 Years
Maximum age
50 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Prior to data collection
• Amenorrhea or irregular cycles
• HC used to manage menstrual dysfunction
• History of gastrointestinal disease/injury
• BMI below 18
Post-collection of data
• Anovulation
• Hormone levels not meeting appropriate reference levels

Study design
Purpose of the study
Prevention
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
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
There are no human studies that have investigated the relationship between gut damage and oestrogen concentrations, however both mouse models (Ricardo-da-Silva et al. 2017) and in vitro studies (Diebel et al. 2015) have shown that damage to cells from ischemic-reperfusion insults can be halved with the application of oestrogen concentrations. The oestrogen concentrations in these studies are higher than would be found in humans, however, we hypothesise that the magnitude of change in oestrogen concentrations between the early follicular and late follicular phases of the menstrual cycle could reduce damage by 15%.
Therefore, based on a post-exercise I-FABP concentrations of 615 pg·ml-1 during the early follicular phase (Van Wijck et al. 2011) and 522 pg·ml-1 during the late follicular phase (85%) and using a standard deviation of 118 pg·ml-1 and a standard alpha (0.05) and beta value (0.8), a sample size of n=13 per group was calculated. Participant numbers are also in accordance with sufficient statistical power to detect a meaningful difference in hormone concentrations across the menstrual cycle (Oosthuyse et al. 2005).

Differences between the early follicular and late follicular phases will be compared using a repeated measures ANOVA (time: pre and post-exercise x menstrual cycle phase). Group (male, female and female oral contraceptive users) x time (pre and post-exercise) main effects and interaction will be analysed using repeated measures ANOVA. If required, more complex analyses to identify interactions between and within groups will include linear regression modelling.
Participants with hormone concentration data that does not meet the criteria for specific menstrual phases will have their data excluded from analysis.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/05/2019
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
39
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
TAS

Funding & Sponsors
Funding source category [1] 301704 0
University
Name [1] 301704 0
University of Tasmania
Country [1] 301704 0
Australia
Primary sponsor type
University
Name
University of Tasmania
Address
University of Tasmania
Newnham campus
Private Bag 1345
Launceston TASMANIA 7001
AUSTRALIA
Country
Australia
Secondary sponsor category [1] 301430 0
None
Name [1] 301430 0
Address [1] 301430 0
Country [1] 301430 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302422 0
Tasmania Health and Medical Human Research Ethics Committee
Ethics committee address [1] 302422 0
Office of Research Services, University of Tasmania, Private Bag 1, Hobart, TAS, 7001
Ethics committee country [1] 302422 0
Australia
Date submitted for ethics approval [1] 302422 0
09/10/2018
Approval date [1] 302422 0
27/03/2019
Ethics approval number [1] 302422 0
H0017613

Summary
Brief summary
Females experience fluctuating steroid hormone profiles throughout their menstrual cycle. During the early follicular (EF) phase, characterised by the onset of bleeding, concentrations of both oestrogen and progesterone are low. Oestrogen increases, and then peaks in the late follicular (LF) phase just prior to ovulation before dropping and then increasing again during the mid-luteal (ML) phase (although not to the same concentrations as seen in the LF phase). Progesterone increases after ovulation, peaking during the ML phase and then decreasing prior to the next EF phase.

There is some evidence that females tolerate gut ischemia (i.e. a lack of oxygen in the gut, often due to blood loss in circumstances such as trauma) better than males. It has been suggested that this is attributable to the protective effects of oestrogen. Interestingly, endurance exercise also causes reduced blood flow (and therefore oxygen) to the gut because blood is redistributed to the working muscles. After an hour of running at 70% of VO2 max blood flow has been shown to be reduced by 80% causing small intestinal injury similar to that induced by trauma. However, to date no study has looked at the menstrual cycle in humans in relation to changes in gut integrity in response to exercise.

The aim of this study is to provide preliminary data on the potential sex dimorphism in susceptibility to intestinal damage during endurance exercise, and if this damage is menstrual cycle dependent. If differences are found, this may have implications for female athletes training and racing during different phases of their menstrual cycle.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 90190 0
Dr Cecilia Kitic
Address 90190 0
University of Tasmania
Newnham campus
Private Bag 1345
Launceston TASMANIA 7001
AUSTRALIA
Country 90190 0
Australia
Phone 90190 0
+61 3 6324 5484
Fax 90190 0
Email 90190 0
[email protected]
Contact person for public queries
Name 90191 0
Dr Cecilia Kitic
Address 90191 0
University of Tasmania
Newnham campus
Private Bag 1345
Launceston TASMANIA 7001
AUSTRALIA
Country 90191 0
Australia
Phone 90191 0
+61 3 6324 5484
Fax 90191 0
Email 90191 0
[email protected]
Contact person for scientific queries
Name 90192 0
Dr Cecilia Kitic
Address 90192 0
University of Tasmania
Newnham campus
Private Bag 1345
Launceston TASMANIA 7001
AUSTRALIA
Country 90192 0
Australia
Phone 90192 0
+61 3 6324 5484
Fax 90192 0
Email 90192 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?
De-identified individual participant data underlying published results only
When will data be available (start and end dates)?
Immediately following publication, no end date determined
Available to whom?
Case-by-case basis at the discretion of Primary Sponsor
Available for what types of analyses?
meta-analyses
How or where can data be obtained?
Access will be subject to approvals by Principal Investigator


What supporting documents are/will be available?

Current supporting documents:


Updated to:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
23720Study protocol  [email protected]
23721Ethical approval  [email protected]

Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.