A Pilot Study: Treatment of Achilles Tendinopathy With Platelet-Rich Plasma Therapy
Condition: Achilles Tendinitis
MeSH terms: Tendinopathy
Study type: Interventional

Summary: 
      The overall goal of this proposal is to correlate ultrasound elastography technique with more
      standard clinically based outcome measures within the setting of a small sample sized group
      of patients affected by moderate-to- severe, chronic (>6months) midsubstance Achilles
      tendinopathy (AT).
    

Detailed description: 
      The main goal for this pilot level study is to correlate ultrasound elastography technique
      with more standard clinically based outcome measures within the setting of a small sample
      sized group of patients affected by moderate-to- severe, chronic (> 6 months) midsubstance
      Achilles tendinopathy (AT). Investigators will conduct a 24-week, 2-arm randomized controlled
      pilot study to determine whether novel elastography techniques (AE) and shear wave imaging
      (SWI), a new quantitative method of ultrasound (US) imaging, correlate with valid clinical
      outcome measures (VISA-A and conventional US). Methods will be based on recently published
      clinical trials of autologous blood injections for treating AT and will incorporate novel US
      outcome measures of Achilles tendon appearance and stiffness, i.e. elasticity. The results of
      this multi-disciplinary pilot study will be used to help plan a separate larger scaled study
      to evaluate the effects of platelet-rich plasma (PRP) therapy for Achilles tendinopathy in
      which elastography will be included as a potential outcome measure and also correlated with
      standard clinical outcome surveys.

      Pain and function will be evaluated by self-report using a validated clinical outcome
      questionnaire (VISA-A). Disease modification will be assessed by novel US-based AE and SWI
      methods for stiffness changes (biomechanical) and correlated with morphologic changes using
      conventional US. A larger study that will evaluate the effects of PRP in healing AT, while
      correlating with elastography assessment, will include a sham injection arm.

      Intervention Subjects assigned to the PRP group will then receive the PRP injection under
      ultrasound guidance. The injection will take about 15 minutes.

      Each subject will undergo a palpatory and ultrasound Achilles tendon exam. Tender areas
      associated with the Achilles tendon will be identified. Physical exam will be followed by
      Achilles tendon ultrasound which will serve as visual guidance for injection.

      At the injection session, the research nurse will perform a single standard antecubital blood
      draw (35 mL). The PRP will be obtained from this sample using a two-stage spinning technique:
      the 1st separates red blood cells from platelets, and the 2nd concentrates the platelets to
      yield approximately 4 mL of concentrated autologous platelet. This layer of platelet rich
      plasma will be placed in the syringe by the centrifuge machine.

      Platelet counts of subjects' whole blood and PRP processed blood will be analyzed. Platelet
      counts in whole blood vary by individual. The optimal quantity of platelets and growth
      factors required for tissue healing is not known, but a clinically effective concentration
      has been described as being greater than 4 times baseline autologous whole blood platelet
      concentrations. Therefore, platelet concentration yield may have important implications in
      clinical outcome correlation. In order to validate consistent platelet concentration yields
      across subjects, investigators will sample 1 mL of whole blood (approximately one lab
      Vacutainer) and an additional 1 mL of platelet rich plasma for lab analysis of platelet
      concentration using a standard lab automated analyzer. This extra 1 ml of whole blood will be
      drawn at the same time that the 35 ml described above is drawn.

      The 3 ml of platelet rich plasma will be injected into the subject's Achilles tendon. The
      specimens will not be kept or stored. The blood will be analyzed on the same day as the
      procedure is being performed. This will not require storing of the specimen and prevent
      erroneous labeling of platelet concentration with a different subject.

      After the injections, the subject will rest for 5 minutes. Participants will be given
      acetaminophen for "as-needed" analgesia and will be telephoned after 3 days to inquire about
      side effects or adverse events. Subjects will be placed in a boot for two weeks with gradual
      return to activity. Subjects will also be provided crutches to be non-weight bearing for 24
      hours.

      Data and Safety Monitoring Plan The data and safety monitoring plan to be implemented in this
      study consists, in part, of a monthly staff meeting to discuss subject enrollment, safety,
      and retention. These meetings are intended to monitor participant study flow from initial
      eligibility assessment to study completion. Standing agenda items for these meetings will be
      side effects, adverse events and participant retention.

      Unanticipated adverse events and complications will be evaluated and treated if necessary by
      the Principal Investigator and the primary Co-Investigator.

      In addition, the following processes will help ensure the timely detection, evaluation and
      treatment:

        1. The Principal Investigator and the primary Co-Investigator will screen subjects for
           adverse events prior to treatment with PRP. Standardized forms will be used for
           monitoring and reporting of adverse events. The PI will be immediately available to
           staff via cell phone in case of a serious adverse event. The PI will immediately report
           serious adverse events to the UW Research Subjects Advocate using standardized forms.
           Reports will be made using the subject identification number without other identifying
           information.

        2. Autologous injection of PRP has been found to be safe. The system being used was chosen
           for its closed system to prevent contamination and for its ease of use. Although safe,
           internal monitoring of PRP injection safety will also be performed. The study
           coordinator will assess each PRP injection subject 3 days after treatment with the
           following question during a brief telephone interview: "Do you think that you have had
           any side effects from the injection you've received?" [If "Yes"] "Please tell me more
           about that." Information regarding side effects and adverse events will be made
           available to the PI, who will decide if the subject requires further medical care.

      Investigators do not expect serious adverse events (SAEs) but are well equipped to manage
      them. Investigators have not seen significant adverse events in combined (UW Radiology and
      Sports Medicine) clinic use of PRP. Subjects with reactions to acetaminophen or injections
      have the option to call study personnel at any time. The PI and the primary Co-Investigator
      will share on-call duty for subjects with adverse events through a pager on a 24/7 basis.
      Subjects who require significant evaluation and care will be referred to the UW Hospital
      Emergency Department.

      Adverse events from a diagnostic ultrasound are extremely unlikely because ultrasound is
      considered to have non-significant risk by the FDA. All study procedures will be monitored
      and documented, and in the unlikely situation where an adverse event occurs, it will be
      followed to resolution.

      The PI(a Board-Certified radiologist) will assess whether the findings should be reported to
      subjects. Findings that would be reported are those considered clinically relevant. Findings
      that are considered normal variants (eg. variant anatomy) or clinically insignificant (eg.
      simple hepatic cyst) will not be reported. Clinically relevant findings will be reported to
      the subject within 24 hours of the scan, and will also be reported to the subject's physician
      according to whether the subject has indicated a desire for this in the consent form.
    

Intervention name(s): Autologous Platelet Rich Plasma; Ultrasound Imaging; Quality of Life Questionnaires
Intervention type(s): Other; Other; Other
Intervention description(s): This procedure will include a single collection of 35 mL of peripheral blood. A two-stage spinning protocol will be used: the 1st separates red blood cells from platelets, and the 2nd concentrates the platelets to yield approximately 4 mL of concentrated autologous platelet. This layer of platelet rich plasma will be placed in the syringe by the centrifuge machine.; A conventional ultrasound in addition to AE and shear wave imaging (SWI) will be administered.; This questionnaire is a self-report of pain and function associated with the Achilles tendon.
Other intervention name(s): Victorian Institute of Sports Assessment - Achilles (VISA-A)
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Achilles; tendinopathy