Regenerative Injection Therapy and Osteoarthritis
Condition: Knee Arthrosis
MeSH terms: Osteoarthritis
Study type: Interventional
Phase: Phase 4

Summary: 
      The objective is to assess the effectiveness of regenerative injection therapy (RIT) to
      relieve pain and restore function in patients with knee osteoarthritis.

      The study design is a randomized controlled trial with cross-over. 40 patients with chronic
      knee osteoarthritis will be randomly assigned to receive exercise therapy for 32 weeks in
      combination with RIT on weeks 0, 4, 8, and 12 or exercise therapy for 32 weeks combined to
      RIT on weeks 20, 24, 28 and 32. The primary outcome is the WOMAC score.
    

Detailed description: 
      The administration of treatment as used in this study was approved by Health Canada and the
      study received ethical approbation by the regional health authority Institutional Review
      Board. Health Canada number: 9427-B2716-21C.

      Participants meeting will be randomized into one of two study groups using opaque sealed
      envelopes in blocks of 6. Each envelope contains a description of the intervention of
      assignment. For group A, the intervention consists of a conventional physiotherapist
      supervised exercise program for 32 weeks in combination with RIT on weeks 0, 4, 8, and 12.
      Intervention for group B includes the supervised exercise program for 32 weeks in combination
      with RIT on weeks 20, 24, 28 and 32 of follow-up. For all study participants, the exercise
      program consists of 4 strengthening exercises for which participants will be asked to perform
      3 sets of 10 repetitions daily.

      RIT injections: The osteo-tendinous junction of both insertion sites of the collateral
      ligaments will be identified. Patients will then receive injections of 1cc of a 15% dextrose
      and 0.6% lidocaine solution free of adrenaline in each of eight administration sites in the
      collateral ligaments. A 5 cc injection of a 20% dextrose and 0.5% lidocaine without
      adrenaline solution will also be administered inside the knee joint. The intra-articular
      injection will be performed using the anterior approach. Solutions are prepared by a hospital
      pharmacist the morning of the injections. Each infiltration will be preceded by a local
      sterilization consisting of three disinfections with a 2% chlorexidine and 4% idopropyl
      alcohol solution.

      Study variables Several measures of functional capacity and pain are used. The primary
      outcome is the Western Ontario and McMaster Universities Osteoarthritis Index of severity of
      osteoarthrosis symptoms (WOMAC version 3.1). This self-administered questionnaire assesses
      pain, disability and joint stiffness using 24 items with 5-point Likert scales. Other
      outcomes included the Brief Pain Inventory (short form), which is administered to assess pain
      intensity and pain-related functional impairment (physical and emotional). More specifically,
      four items assess the intensity of current pain and pain at its least, worst, and average
      during the past day on scales from 0 ("no pain") to 10 ("pain as bad as you can imagine").
      Seven more items measure pain-related functional interference in different domains (general
      activity, mood, walking ability, normal work, relations with other people, sleep, and
      enjoyment of life) rated from 0 ("does not interfere") to 10 ("interferes completely").
      Participants will also rate their pain with the Wong-Baker Faces Pain Rating Scale, a series
      of 6 faces anchored at 0 for "no hurt" and 5 for "hurts worst". After being instructed that
      each face is for a person who feels happy because he has no pain or sad because he has some
      or a lot of pain, participants chose the face that best describes how they feel. Participants
      also rate their pain with a simple descriptive intensity scale with 7 adjectives (no pain,
      mild pain, moderate pain, severe pain, very severe pain, and worst pain possible), a numeric
      distress scale with anchors 0 for "no pain" and 10 for "unbearable pain", and a visual
      analogue scale with the words "no pain" and "pain as bad as could possibly be" at the left
      and right ends of the line, respectively. The Timed Up-and-Go Test will be used to evaluate
      functional capacity. Participants start in a sitting position (with hands resting on the arms
      of an armchair of standard height), stand up, walke 3 meters, turn around, and walk back to
      sit down on the chair again. The timing starts when the participant's back comes off the
      chair, and stops when their buttocks touch the seat of the chair.

      Patients' severity of knee osteoarthritis will be assessed by a radiologist using the
      Kellgren-Lawrence grading scale. Anteroposterior radiographs of the knee are to be taken
      prior to enrollment in the study.

      Follow up Participants will meet with research assistants (research nurses and family
      medicine residents) at the onset of the study, every four weeks of the subsequent 32 weeks of
      intervention, and four weeks after the intervention. At each of those visits, participants
      will be asked to fill in measurement questionnaires. Research assistants will also
      investigate the presence of side effects or complications and remind participants that the
      research protocol restricts them from taking any anti-inflammatory medication throughout the
      32 weeks of intervention. Participants will also meet the physiotherapist every four weeks to
      review exercises. At the onset of the study, participants will receive a study calendar
      detailing each of their appointments. In addition, patients will receive an appointment card
      at the end of each visit. This card provides the time of the next visit, contact information,
      as well as a list of conditions for which participants should contact the study center. If a
      participant presents a sustained deterioration of symptoms or function, or experiences
      undesirable side effects, the presumed contributing part of the treatment will be
      discontinued.
    

Intervention name(s): Regenerative injection therapy; Exercise
Intervention type(s): Procedure; Behavioral
Intervention description(s): Injections of 1cc of a 15% dextrose and 0.6% lidocaine solution free of adrenaline in each of eight administration sites in the collateral ligaments and a 5 cc injection of a 20% dextrose and 0.5% lidocaine without adrenaline solution inside the knee joint.; the exercise program consists of 4 strengthening exercises for which participants are asked to perform 3 sets of 10 repetitions daily
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment