Non-Insertional Achilles Tendinopathy Clinical Trial
Official title:
Functional Improvement and Ultrasound Tissue Characterisation of the Achilles Tendon Following Sodium Hyaluronate Injection for Plantaris Friction Syndrome
This is a study to assess the benefit of sodium hyaluronate (Ostenil) injection for plantaris friction syndrome (PFS) associated with midportion Achilles tendinopathy. Functional outcome scores will be recorded prior to treatment and at regular intervals up to 2 years. Changes in tendon structure will be assessed using ultrasonographic tissue characterisation (UTC). UTC will be performed prior to treatment and also at regular intervals up to 6 months following injection.
Introduction Midportion Achilles tendinopathy is a common source of disability, with typical
features including pain, swelling and dysfunction [Roche]. The causes are multifactorial
[Roche]. First line treatment is typically non operative and includes an eccentric loading
program [Alfredson-1998], high volume injection [Chan], platelet rich plasma [de Vos JAMA
2010], sclerosing agent injections [Alfredson-2005] , shock wave therapy [Lynen][Saxena] and
for resistant cases, surgery [Alfredson-2011].
Plantaris friction syndrome (PFS) One possible cause of midportion Achilles tendinopathy is
plantaris friction syndrome (PFS). In this subset of patients, the pain is located to the
postero-medial aspect of the Achilles tendon. The plantaris tendon is a small vestigial
tendon originating from the lateral femoral condyle, crossing obliquely to the medial side
of the Achilles tendon and inserting into the medial side of the calcaneum. The anatomy at
the insertion is highly variable. Over 80% of plantaris tendons insert separately to the
Achilles tendon [Daseler]. Biomechanical evidence suggests that the plantaris tendon is
stiffer and stronger than the Achilles tendon [Lintz]. Under load therefore, differential
movement between the tendons may occur. Subsequently the plantaris tendon can become
tendinopathic and thickened. Adhesions may develop between it and the adjacent Achilles
tendon [Bedi], initiating medial midportion Achilles tendinopathy. Sensitization of the
nerve endings in the fat layer between the Achilles and plantaris has also been
demonstrated. The optimal treatment of PFS is currently unclear. Treatments include
physiotherapy, injection and surgical excision
[Bedi][Pearce][Weinberg][Calder-2014][Alfredson-2011].
Sodium Hyaluronate One potential treatment is injection with sodium hyaluronate which is a
viscosupplement solution. It has primarily been used for joint lubrication in arthropathy,
but can also be used for tendinopathy [Lynen]. Ostenil Tendon is a sodium hyaluronate
solution that potentially acts in several ways to reduce pain. One mode is to act as a
lubricant between tendons or between the tendon and its sheath [Akasaka 2005][Akasaka
2006][Nishida][Kumar][St Onge]. It may also promote tendon healing [Chen][Yagishta].
According to unpublished work, Ostenil Tendon significantly reduced pain at 6 weeks for
peroneal and also midportion Achilles tendinopathy [Company literature]. It may also act as
a medium to allow free passage of nutrients to the tendon [Hagberg]. Sodium hyaluronate
injection placed in the interval between the plantaris tendon and Achilles tendon could
potentially reduce friction and subsequently pain. Although the effect of sodium hyaluronate
injections have been reported in the hip and knee, no previous studies have reported its
efficacy for PFS. The primary aim of the current study is to assess the impact of sodium
hyaluronate injections in patients with PFS.
Ultrasound tissue characterization Methods of assessing the Achilles tendon for tendinopathy
continue to be debated. Common methods include ultrasound and magnetic resonance imaging
[Khan][Astrom]. A novel assessment tool is ultrasound tissue characterization (UTC) which
uses ultrasound to quantify tendon structure [van
Schie][Docking-2015][Docking-2016][Rosengarten][Bedi].
Structural integrity of the tendon matrix is categorized in four echo types (1-green,
2-blue, 3-red, 4-black). Echo types 1 and 2 reflect aligned fibrillar structure, whereas
types 3 and 4 indicate disorganised tissue [Bedi]. The entire length of the tendon can be
analyzed with a minimum detectable difference in structure to be 1% [Docking-2015]. Bedi et
al showed significant improvement in UTC following excision of plantaris for midportion
Achilles tendinopathy [Bedi]. However this study was limited because UTC images were not
performed at a uniform time pre- and post- surgery [Bedi]. Masci et al found improvement in
UTC echo-structure at 6 month follow-up post plantaris excision combined with improvement in
VISA-A scores [Masci]. It is debated as to whether fibrillar integrity and matrix
organisation correlate with symptoms. For example, a study in elite Australian football
players showed that UTC changed following pre-season training, but all players remained
asymptomatic at the start and end of the study [Rosengarten]. Ultrasound studies have also
questioned the relationship of tendon structure in tendinopathy and patient function
[Khan][McAuliffe]. In a study of gymnasts, clinical assessment has only moderate correlation
with ultrasound and MR appearances [Emerson].
Given the novelty of UTC for the Achilles tendon, the secondary aim of this study is to
assess whether UTC changes following treatment for PFS and to correlate any changes with
functional outcome scores.
Aims summary
1. To determine changes in Achilles tendon matrix structure using UTC before and after
treatment (6 month follow up)
2. To assess medium term (2 years) effectiveness of a sodium hyaluronate injection in the
space between the plantaris and Achilles tendons for midportion Achilles tendinopathy
which is associated with PFS.
3. To correlate UTC changes with functional scores
Hypothesis The alternate hypotheses are that sodium hyaluronate injection improves both 1)
function and 2) structure of the Achilles tendon for PFS.
Outcome measures
- Ultrasonographic tissue characterisation (UTC)
- Functional scores - Victorian Institute of Sports Assessment-Achilles (VISA-A)
[Robinson] and Foot and Ankle Outcome scores (FAOS)
Methods This will be a single centre prospective case series of patients in whom PFS has
been diagnosed based upon clinical examination by a Consultant foot & ankle surgeon,
physiotherapist and imaging. Patients will be prospectively followed up with pre and post
intervention patient reported outcome scores.
Sample Population 33 patients diagnosed with PFS will be identified and invited to
participate in the study once the decision has been made to treat with sodium hyaluronate.
Inclusion Criteria Patients aged 18-75 years Able to provide informed consent Diagnosis of
PFS requiring sodium hyaluronate injection Able to follow physiotherapy instructions
Exclusion Criteria Previous Achilles tendon surgery Previous injection therapy for Achilles
midportion tendinopathy Age < 18 >75 years Active local infection Active bleeding disorder
or anticoagulant therapy Allergies to lignocaine or sodium hyaluronate Active deep vein
thrombosis
Patient Recruitment and Consent All patients will be given the information sheet regarding
the study and will be consented by the CI or the Fortius foot and ankle fellow. All be
patients will be recruited and treated at the Fortius Clinic.
Proposed treatment will include one or two sodium hyaluronate (Ostenil Tendon) injections.
Physiotherapy is a routine part of current treatment, usually provided off site.
Injection protocol All injections will be carried out by a Consultant Radiologist at the
Fortius Clinic. Approximately 3-5mm of 1% lignocaine will be injected to create a plane
between Plantaris and the medial Achilles tendon. Subsequently, 2-3ml of Ostenil Tendon
(sodium hyaluronate) will be injected into the space between the Achilles and plantaris
tendons.
UTC assessment UTC assessment at 6 and 12 weeks is a routine part of our current treatment
protocol for PFS and allows guidance of treatment. Patients will have pre and post treatment
UTC assessment of the Achilles tendon. For the purposes of the study, an extra UTC
assessment will be performed at 6 months, during part of their routine clinical follow up
appointment. This final UTC assessment will be provided free to the patients. All UTC
assessments will be conducted by the same experienced physiotherapist.
Follow up Patient reported outcome scores will be completed prior to treatment and at 6
weeks, 3 months,6 months, 1 and 2 years. Outcome scores at 1 and 2 years will be performed
online via an automated email system.
UTC will be conducted at 6 weeks, 3 months and 6 months.
Ethical Issues:
Patients will be free to choose to participate or not in the study. If they choose not to
participate it will not affect their treatment in any way.
No patient or volunteer will take part in the study without giving written informed consent
and we will exclude those patients who are unable to give this consent.
Legal Issues:
There are no legal issues identified that will affect this study.
Management issues:
This study will take place at the Fortius Clinic, which is a private clinic. The patients
included would be receiving one or two sodium hyaluronate injections, and two UTC
assessments as part of the routine treatment of PFS. They will be charged for this as
normal. There will be no additional charge for the final UTC assessment at 6 months.
Risks:
Patients agreeing to take part in the study will be receiving the routine treatment for PFS
that they would be receiving even if the study was not taking place. There are therefore no
additional risks to the patient.
Data collection All data collection will be done within the premises of the Fortius clinic
by members of the clinical team, which includes a physiotherapist who works on site for the
Tendon Performance Clinic. In addition to the outcome score and UTC data information
regarding patient demographics, medical history and treatment will also be collected.
Data confidentiality Data will be stored in Fortius/Tendon Performance Clinic computers
which are password protected and comply with information governance guidelines. No one
outside the clinical team will have access to the data.
Any information that leaves the clinic will have patient identifiable information removed.
All of the results will be analysed and published using anonymous data only. Details about
patient's involvement in the study will also be recorded in patients' medical records held
by the Fortius Clinic/Tendon Performance Clinic.
Power analysis In 18 asymptomatic elite Australian football players, UTC demonstrated
improvement in Achilles tendon structure over a 5 month period following pre-season training
[Docking-2016]. Bedi et al reported UTC changes following Plantaris excision and ventral
paratendinous Achilles tendon scraping in athletes. In 11 patients, the fibrillar structure
of the Achilles tendon improved from 90 to 96%, SD 8% p=.04. Mean VISA-A scores improved
from 51 to 95, SD 12, p=.0001. Regarding sodium hyaluronate injection, only one study was
found assessing its use for midportion Achilles tendinopathy [Lynen]. Lynen et al compared
two paratendinous injections with three ESWT treatments given at weekly intervals in 62
patients. No previous studies have assessed its use for PFS.
Considering the limited evidence available, we estimate the sample size required to
demonstrate improvements in UTC (assuming change in type 1 and 2 echo types from 90% to 96%,
SD 8%) to be at least 28 patients. With an expected drop out rate of 15%, we plan to recruit
33 patients to the study.
Statistical analysis Analyses will be conducted using a statistical package. A paired t test
will be used to compare pre and post treatment VISA-A scores. UTC results will be compared
using Wilcoxon signed rank test (non parametric data). A p value of 0.05 will be defined as
statistically significant.
;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Active, not recruiting |
NCT00835939 -
Treatment for Achilles Tendinopathy
|
Phase 2/Phase 3 |