Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001166763
Ethics application status
Approved
Date submitted
16/08/2022
Date registered
24/08/2022
Date last updated
21/05/2024
Date data sharing statement initially provided
24/08/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Does anterior cruciate ligament (ACL) injury impair the molecular pathways responsible for building muscle?
Scientific title
Does anterior cruciate ligament (ACL) injury impair the molecular pathways responsible for building muscle?
Secondary ID [1] 307791 0
None
Universal Trial Number (UTN)
U1111-1281-6714
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anterior Cruciate Ligament injury 327369 0
Condition category
Condition code
Injuries and Accidents 324492 324492 0 0
Other injuries and accidents
Musculoskeletal 324516 324516 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
A within-participant cross-sectional study will permit investigation of differences in exercise-induced molecular pathway within the same participant between his/her limbs (with/without a prior ACL injury) at rest and immediately following a single bout of strength/rehabilitation exercise.
Demographic data will be collected prior to the observational testing sessions via online surveys. To assess a participant’s knee joint symptoms and function in daily living activities the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form will be completed by all participants. To assess a participant’s psychological readiness to return to sport after ACL injury and reconstruction surgery the Anterior Cruciate Ligament Return to Sport After Injury (ACL-RSI) scale will be completed. Additionally, participants will rate their ability to partake in sport/activity both pre- and post-injury using the Tegner Scale. Details on the surgical approach used for ALC reconstruction, as well as any other co-morbidities, will also be ascertained from participants.
Participants will be required to attend three observational sessions; a familiarisation (during which the leg press 1RM will be measured), a magnetic resonance imaging (MRI) scan, and the strength training session. All three sessions will occur within 7-14 days. Each session will take up to 2 hours to complete, the total observation period will not exceed 6 hours.
Skeletal muscle protein content and activation of key strength training signalling pathways will be measured pre- and post-strength training session. Lower limb muscle morphology and leg press 1-repetition maximum (1RM) will be measured during the familiarisation session. All sessions will be conducted by highly trained researchers in this field.
Unilateral leg press 1RM will be determined for both the uninjured and previously injured limb. Each limb will complete a warm up with a load that is equivalent to a 5 on a 1-10 rating of perceived exertion (RPE) scale, for between 3-5 repetitions. The load will incrementally increase (by between approximately 5-20kg) and the repetitions will decrease until the load that an individual cannot successfully lift for one repetition is found. The participant will be given one more opportunity to lift this load and if they fail to lift the load the highest load successfully lifted for one repetition will be considered the 1RM. Participants will be given a minimum of 2 mins between one repetition maximum efforts.
During the strength training session, all participants will perform six sets of eight repetitions of a unilateral leg press exercise using a load equivalent to 80% 1RM for each leg (a total of 12 sets per participant). Each set will be completed one leg at a time, with limbs completing sets in an alternating order. The limb which completes the first set will be randomised between individuals using a coin flip. Each limb will be given a 90 second rest between sets. The duration of the strength training sessions will be approximately 30 minutes.
Intervention code [1] 324251 0
Not applicable
Comparator / control treatment
Uninjured lower limb (in comparison to the lower limb which sustained the ACL injury)
Control group
Active

Outcomes
Primary outcome [1] 332317 0
Activation of key strength training signalling pathways measured with quadriceps muscle biopsy
Timepoint [1] 332317 0
Measured during the strength training session, immediately before and after exercise
Primary outcome [2] 332347 0
Skeletal muscle protein content as measured with quadriceps muscle biopsy
Timepoint [2] 332347 0
Measured during the strength training session, immediately before and after exercise
Secondary outcome [1] 413002 0
Lower limb muscle morphology as measured by a 3-Tesla (3T) magnetic resonance imaging system. Contiguous T1-weighted axial MRIs (transverse relaxation time: 2500 ms; echo time: 14ms; field of view: 220 x 360 mm; slice thickness: 5mm; interslice distance: 0mm) will be taken of both limbs, beginning at T12, L1 intersection and finishing distal to the malleoli.
Timepoint [1] 413002 0
Measured during the MRI scan session, prior to the strength training session.
Secondary outcome [2] 413003 0
Leg press 1-repetition maximum (1RM).
Timepoint [2] 413003 0
Measured during the familiarisation session.

Eligibility
Key inclusion criteria
1. Male or female
2. Aged between 18 to 35 years
3. One leg sustained an ACL injury within the last 5-years, but can safely complete lower limb strength training
4. BMI 18.5-29.9m2
Minimum age
18 Years
Maximum age
35 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Any lower limb injury in the past 24-months that influences the quadriceps responses to exercise (e.g. muscle strain)
2. Known cardiovascular disease or diabetes
3. Known bleeding disorder (i.e. hemophilia A [factor VIII deficiency], hemophilia B [factor IX deficiency], von Willebrand disease, or other rare factor deficiencies including I, II, V, VII, X, XI, XII and XIII)
4. Major or chronic illness that impairs mobility or eating/digestion
5. Taking prescription medications (i.e. beta-blockers, anti-arrhythmic drugs, statins, insulin sensitising drugs, or drugs that increase the risk of bleeding [i.e. anticoagulants, antiplatelets, novel oral anticoagulants [NOAs], nonsteroidal anti-inflammatory drugs [NSAIDs], selective norepinephrine reuptake inhibitors [SNRI], or selective serotonin reuptake inhibitors [SSRIs])

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Sample size:
A sample size of 12 participants is sufficient to test our hypothesis based on previous research investigating changes in muscle signalling pathways following strength training exercise (effect size = 0.78, a-level = 0.05, 1-ß = 0.80). Assuming a dropout of rate of 20% we aim to recruit 15 participants to ensure we are sufficiently powered.

Descriptive statistics (e.g., mean and standard deviation) will be used to describe the sample (age, height, weight, IDKC score, ACL-RSI score, surgical approach, time since reconstructive surgery).

To determine if the primary outcome measure changes following the strength training session (pre to post) and if the change is different in uninjured and previously ACL injured limbs a linear mixed model with fixed factors of limb (uninjured or injured) and time (pre- or post-training) and random factor of participant ID. Where significant effects (main or interaction) are detected a post-hoc t-test will be used to identify where the significant differences exist. To determine if the secondary outcome measures are different between uninjured and injured limbs a one-tailed dependent t-test will be used. Significance will be set at p < 0.05 and Cohen’s d effect sizes will be calculated where appropriate.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/09/2022
Actual
1/09/2022
Date of last participant enrolment
Anticipated
1/08/2023
Actual
30/08/2023
Date of last data collection
Anticipated
31/08/2023
Actual
30/09/2023
Sample size
Target
12
Accrual to date
Final
12
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 38289 0
3065 - Fitzroy

Funding & Sponsors
Funding source category [1] 312061 0
Government body
Name [1] 312061 0
Defence Science Institute
Country [1] 312061 0
Australia
Primary sponsor type
Individual
Name
Assoc Prof David Opar
Address
Sports Performance, Recovery, Injury & New Technologies (SPRINT) Research Centre
Australian Catholic University
17 Young Street, Fitzroy VIC 3065
Country
Australia
Secondary sponsor category [1] 313565 0
Individual
Name [1] 313565 0
Prof John Hawley
Address [1] 313565 0
Mary MacKillop Institute for Health Research
Australian Catholic University
5/215 Spring St, Melbourne VIC 3000
Country [1] 313565 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311470 0
Australian Catholic University Human Research Ethics Committee
Ethics committee address [1] 311470 0
Ethics committee country [1] 311470 0
Australia
Date submitted for ethics approval [1] 311470 0
Approval date [1] 311470 0
04/01/2022
Ethics approval number [1] 311470 0
2021-278H

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

Contacts
Principal investigator
Name 121210 0
A/Prof David Opar
Address 121210 0
Sports Performance, Recovery, Injury & New Technologies (SPRINT) Research Centre
Australian Catholic University
17 Young Street, Fitzroy VIC 3065
Country 121210 0
Australia
Phone 121210 0
+61 399533742
Fax 121210 0
Email 121210 0
[email protected]
Contact person for public queries
Name 121211 0
Ashleigh Homer
Address 121211 0
Sports Performance, Recovery, Injury & New Technologies (SPRINT) Research Centre
Australian Catholic University
17 Young Street, Fitzroy VIC 3065
Country 121211 0
Australia
Phone 121211 0
+61 3 99533502
Fax 121211 0
Email 121211 0
[email protected]
Contact person for scientific queries
Name 121212 0
David Opar
Address 121212 0
Sports Performance, Recovery, Injury & New Technologies (SPRINT) Research Centre
Australian Catholic University
17 Young Street, Fitzroy VIC 3065
Country 121212 0
Australia
Phone 121212 0
+61 399533742
Fax 121212 0
Email 121212 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
De-identified individual participant data will not be readily available. Any questions around data should be sent to the PI.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
16928Ethical approval  [email protected]
16929Study protocol  [email protected]
16930Informed consent form  [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.