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Trial registered on ANZCTR


Registration number
ACTRN12618000762257p
Ethics application status
Not yet submitted
Date submitted
1/05/2018
Date registered
7/05/2018
Date last updated
7/05/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Can Autologous Conditioned Plasma Therapy Enhance Hamstrings Healing After Anterior Cruciate Ligament Reconstruction?
Scientific title
Improving Donor Site Musculotendon Regeneration following Quadrupled Semitendinosus Anterior Cruciate Ligament Reconstruction through Autologous Conditioned Plasma Therapy
Secondary ID [1] 294658 0
None
Universal Trial Number (UTN)
U1111-1212-5151
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anterior Cruciate Ligament Deficiency 307507 0
Condition category
Condition code
Musculoskeletal 306589 306589 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
One group receives standard semitendinosus quadruple bundle Anterior Cruciate Ligament Reconstruction (ACLR), while the second group receives similar ACLR combined with Autologous Condition Plasma (ACP) administered to the donor site during surgery. The standard ACLR surgery group is referred to as "ACLR", whereas the group with ACLR combined with ACP is referred to as "ACLR+". For both groups, a quadruple bundle ipsilateral semitendinosus autograft is performed using an anteromedial portal technique. This is a standard surgical procedure to treat ACL deficiency and takes approximately 45 minutes. The local anaesthetic administered is 20ml 0.75% of Bupivicaine. In the ACLR+ group, the surgical procedure will be augmented by application of Arthrex’ ACP therapy to the donor site and repairing the Sartorius fascia after harvest. The orthopaedic surgeon administers the ACP. For the ACP therapy, 10ml of the patient's own venous blood is aspirated and the syringe centrifuged in a proprietary closed unit (Arthrex Medical Company) for 5 minutes. The red blood cells are discarded, and the supernatant containing ACP (with additional CaCl to activate the ACP and local anaesthetic) is deposited onto the tendon excision site from pes anserinus to proximal terminus of excision. No adverse consequences are anticipated by using the ACP therapy.

Following surgery, all patients will be enrolled in a standardized physiotherapy program and will continue this treatment until completion (~6-9 months clinical recommendation). In the first month, participants will attend their own physiotherapist clinic for a minimum of two one-on-one sessions per week, with each session lasting one hour. For the remaining rehabilitation, participants are required to visit their physiotherapist at least once every two weeks for one hour. During this time, participants are expected to complete their physiotherapy exercises outside of the clinic and visit the physiotherapist for re-assessment.
The goal of the rehabilitation and exercises will vary depending on time after surgery. The first month of rehabilitation will involve restoring range of motion to the knee joint and strengthening of hamstring and quadriceps muscles (e.g., cycling). Months 2-3 include closed chain knee strengthening exercises (e.g., leg press) and isometric strengthening. The remaining rehabilitation will aim to restore balance through isokinetic and proprioception exercises, and eventually progress to functional movements such as running and jumping. In each phase, progression will be added by increasing resistance, increasing task complexity, and reducing stability. Adherence will be monitored for the ACLR+ group through an electronic questionnaire. As the ACLR group is a retrospective control, we will assess adherence through a post-hoc questionnaire asking about frequency of physiotherapy vists per week and the total duration of treatment.
Intervention code [1] 300955 0
Treatment: Surgery
Comparator / control treatment
In addition to the standard ACLR group serving as the control for the ACLR+ group, the unaffected contralateral limb serves as the control for the affected limb within both groups. Thus, we will compare outcome measures at 1-year post-surgery (i.e., muscle function and knee health) both within participants (i.e., between affected vs unaffected limbs) and between surgery types (i.e., ACLR vs ACLR+).
We will retrospectively recruit participants for the ACLR group from a database of patients who have received ACLR within the last year. Participants who meet the inclusion criteria will be invited to attend the laboratory for testing 1-year post-surgery. The ACLR+ participants will be recruited prospectively (i.e., patients coming for surgery after recruitment date begins) and offered the alternative treatment. Participants can still choose conventional treatment and will in no way be coerced into choosing the ACP application. Thus, recruitment will be staggered as 23 people will not rupture their ACL and have surgery at the same time.
Control group
Historical

Outcomes
Primary outcome [1] 305585 0
Change in Magnetic Resonance Imaging (MRI)-based measures of musculotendon volume for the donor muscles, semimembranosus, gracilis, sartorius, and biceps femoris bilaterally.
Timepoint [1] 305585 0
1-year following Anterior Cruciate Ligament Reconstruction (ACLR)
Primary outcome [2] 305765 0
Change in Magnetic Resonance Imaging (MRI)-based measures of musculotendon cross-sectional area for the donor muscles, semimembranosus, gracilis, sartorius, and biceps femoris bilaterally.
Timepoint [2] 305765 0
1-year following (ACLR)
Primary outcome [3] 305766 0
Change in Magnetic Resonance Imaging (MRI)-based measures of musculotendon length for the donor muscles, semimembranosus, gracilis, sartorius, and biceps femoris bilaterally.
Timepoint [3] 305766 0
1-year following (ACLR)
Secondary outcome [1] 345839 0
Change in passive semitendinosus stiffness at different joint angles assessed using ultrasound-based elastography
Timepoint [1] 345839 0
1-year following ACLR
Secondary outcome [2] 345840 0
Change in bilateral donor muscle, semimembranosus, gracilis, sartorius, and biceps femoris muscle strength. Strength will be assessed using isometric and isokinetic knee flexion/extension and knee internal/external rotation tests on a dynamometer. This is a composite secondary outcome.
Timepoint [2] 345840 0
1-year following ACLR
Secondary outcome [3] 345841 0
Change in passive anterior-posterior knee laxity using a KT-2000 arthrometer
Timepoint [3] 345841 0
1-year following Anterior Cruciate Ligament Reconstruction
Secondary outcome [4] 345842 0
Change in patient-perceived knee function using the following questionnaires, Knee Injury and Osteoarthritis Outcome Score, Cincinnati Knee Rating System, and Knee Injury and Osteoarthritis Outcome Score (KOOS).
Timepoint [4] 345842 0
1-year following ACLR
Secondary outcome [5] 346416 0
Change in passive semitendinosus fibre lengths at different joint angles assessed using ultrasound-based elastography
Timepoint [5] 346416 0
1-year following ACLR
Secondary outcome [6] 346417 0
Change in patient-perceived quality of life using the 36-item Short Form Health Survey (SF-36).
Timepoint [6] 346417 0
1-year following ACLR

Eligibility
Key inclusion criteria
Aged 18-35 years;
Acute rupture of anterior cruciate ligament with non-pathological menisci;
Will have reconstruction within six months of injury;
No diseases that affect cardiovascular or musculoskeletal health
Body mass index ranged between 18.5 and 29.9 as this corresponds to the World Health Organisations guidelines for healthy (18.5-24.9) and overweight (25-29.9) weight ranges in adults.
Minimum age
18 Years
Maximum age
35 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Injuries to other knee articular tissues (e.g., menisci, posterior cruciate ligament) secondary to ACL;
Not undertaken pre-habilitation therapy;
Currently smoking or ceased smoking in last 6 months;
Prior lower-limb Autologous Conditioned Plasma therapy;
Metabolic bone or blood disorders;
Cardiac disorders;
Previous lower-limb trauma;
Ferrous metal implant;
Currently pregnant or planning to be pregnant during the study period);
Osteoporotic;
Not taking recreational drugs or consuming large amounts of alcohol on a regular basis (> 3 nights per week).

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
Other
Other design features
Retrospective controls and the experimental arm is prospective. Nobody will be blinded to participant allocation.
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Using the reported change in muscle cross-sectional area from Konrath et al 2016 (AJSM, 44(10), 2589-2598), we estimated the effect of standard ACLR on donor musculotendon atrophy and strength loss to be ~1 when using the contralateral muscles as controls. To achieve 95% power to detect differences in muscle cross-section area between affected and unaffected limbs at an alpha of 0.05, we require 46 participants total, with each group containing 23 participants. Accounting for dropout and data errors, we aim to collect 26 in each group.
We will compare the differences between ACLR and intact contralateral limbs for the two groups (ACLR vs ACLR+) for all outcome measures using generalized linear models, and where possible make comparisons to the report by Konrath et al (2016).

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment postcode(s) [1] 22487 0
4217 - Benowa

Funding & Sponsors
Funding source category [1] 299275 0
Commercial sector/Industry
Name [1] 299275 0
Arthrex, Inc
Address [1] 299275 0
1370 Creekside Boulevard
Naples, FL. 34108
Country [1] 299275 0
United States of America
Primary sponsor type
University
Name
Griffith University
Address
Office for Research, Gold Coast campus, Griffith University, QLD 4222 Australia
Country
Australia
Secondary sponsor category [1] 298544 0
None
Name [1] 298544 0
Address [1] 298544 0
Country [1] 298544 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 300186 0
Ethics committee address [1] 300186 0
Ethics committee country [1] 300186 0
Australia
Date submitted for ethics approval [1] 300186 0
20/05/2018
Approval date [1] 300186 0
Ethics approval number [1] 300186 0

Summary
Brief summary
Purpose and Hypothesis:
The purpose of this project is to examine whether Autologous Conditioned Plasma (ACP) therapy can enhance semitendinosus healing after Anterior Cruciate Ligament (ACL) reconstruction. Muscle-tendon regeneration and knee function will be compared 1-year post-surgery between a group receiving ACL reconstruction and a group receiving ACL reconstruction combined with Arthrex’ ACP application to the donor site.
Previous studies have found donor hamstring muscles experience substantial wasting (e.g., reduce in size and strength) following ACL reconstruction. Specifically, semitendinosus and gracilis muscles and muscle-tendons experience little regeneration, retraction of the muscle belly, atrophy, strength deficits, and impairments of function. We hypothesize ACL reconstruction combined with ACP application, referred to as “ACLR+”, will result in better muscle and tendon regeneration and improved knee function at 1 year following surgery. Specifically, we hypothesize that individuals receiving ACLR+ will have muscle-tendon morphology (i.e., muscle-tendon volumes and cross-sectional areas) and muscle quality (i.e., fat content and stiffness) similar to the muscles and tendons in the untreated contralateral leg. Conversely, those receiving standard ACL reconstruction will have a significantly smaller and lower quality donor muscle and tendons compared to the contralateral leg. Further, we hypothesize that at 1-year post-surgery, donor tendon regeneration will be similar to the unaffected contralateral side in ACLR+ patients, but regeneration will be worse in those receiving standard ACL reconstruction. In this instance, normal regeneration is identified by similar muscle stiffness, knee strength, and knee function between the two legs, whereas worse regeneration is identified by the affected muscle-tendon being less stiff, weaker, and having impaired function compared to the unaffected leg.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 82838 0
Dr David John Saxby
Address 82838 0
Griffith University
Clinical Sciences 1, Gold Coast Campus, Parklands, Queensland, 4222
Country 82838 0
Australia
Phone 82838 0
+61755528917
Fax 82838 0
Email 82838 0
d.saxby@griffith.edu.au
Contact person for public queries
Name 82839 0
Dr David John Saxby
Address 82839 0
Griffith University
Clinical Sciences 1, Gold Coast Campus, Parklands, Queensland, 4222
Country 82839 0
Australia
Phone 82839 0
+61755528917
Fax 82839 0
Email 82839 0
d.saxby@griffith.edu.au
Contact person for scientific queries
Name 82840 0
Dr David John Saxby
Address 82840 0
Griffith University
Clinical Sciences 1, Gold Coast Campus, Parklands, Queensland, 4222
Country 82840 0
Australia
Phone 82840 0
+61755528917
Fax 82840 0
Email 82840 0
d.saxby@griffith.edu.au

No information has been provided regarding IPD availability
Summary results
No Results