Safety and Efficacy of Botulinum Toxin A Injection in Patients With Painful Artificial Knee Arthroplasty (TKA)
Condition: Knee Pain
MeSH terms: Pain
Intervention: Botulinum toxin A; Normal Saline
Intervention description: 100 units of Botulinum toxin A in 5 cc of normal saline in the Painful TKA at screening visit; Single Intra-articular Injection of 5 cc of normal saline in the Painful TKA at screening visit
Intervention MeSH terms: Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 54.0
Sex: All
Healthy volunteers: No
Keywords: Painful Knee Arthroplasty; Botulinum Toxin A; Randomized Controlled Trial; Pain and Function

Summary:

      Primary Total Knee joint replacement surgery is highly successful surgery for relieving pain
      and improving function in patients with disabling arthritis. Unfortunately, like all
      biomedical devices, prosthesis failure is a complication of knee replacement surgery that
      leads to disabling pain, stiffness and loss of function. Approximately 1% of the knee
      replacements fail every year leading to a 20% failure rate over 20 years. The common causes
      of failure of prosthetic joint are infection, loosening, trauma or wear of the prosthesis.
      Currently, a revision surgery is the best option for long term pain relief (analgesics or
      other pain medications are options but are of limited benefit). Surgery may not be feasible
      in patients due to advancing age, other medical conditions and surgical/technical
      difficulties or patient's choice. In addition, the results from revision surgery are not as
      good as the initial knee joint surgery. Therefore, there is a great need for a novel,
      targeted therapy that provides an option to patients who are unfit, unable, or unwilling to
      undergo surgery.

      In the investigators' recent pilot study, a single injection of Botulinum toxin A (Botox) in
      painful natural knee, ankle and shoulder joints of patients with various types of arthritis
      led to significant and durable improvement in pain and function and was safe to use. The
      investigators propose this 6-month study to compare pain relief, improvement of function and
      safety of an injection of Botulinum toxin compared to placebo in patients with a painful
      prosthetic knee joint. Both patients and investigators will be blinded to the treatment
      assignment to a patient until the study is completed. The investigators will assess the
      amount and duration of pain relief, improvement in function and short term safety of
      Botulinum toxin using standard validated measures. Patients will be evaluated at baseline, 2
      weeks, 1-, 2-, 3-, 4- and 6-months after a single injection of either placebo or BoNT/A in
      the hip or knee prosthesis. The six-month follow-up is to assess the duration of meaningful
      pain relief. If successful, this will offer a new treatment option for patients with a
      chronically painful knee prosthetic joint, provide more insight into the origin and cause of
      pain in prosthetic joints and direct future investigations in new directions.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female subjects, 18 years of age or older.

          -  Written informed consent and written authorization for use or release of health and
             research study information have been obtained.

          -  Subject has chronic Prosthetic knee joint pain for more than 3 months.

          -  Subject has pain 6 or greater on a 10 point Numerical Pain Rating scale

          -  Ability to follow study instructions and likely to complete all required visits.

          -  Negative urine pregnancy test on the day of treatment prior to the administration of
             study medication (for females of childbearing potential). (if applicable)

          -  Negative infectious etiology workup (joint aspiration, serological parameters such as
             Erythrocyte Sedimentation Rate (ESR) or C-reactive protein (CRP) and clinical
             examination).

          -  Patients who were considered not to be candidates for Prosthetic knee joint revision
             surgery and have failed traditional treatments including oral pain medications, as
             determined by referring orthopedic surgeon

        Exclusion Criteria:

          -  Use of aminoglycoside antibiotics, curare-like agents, or other agents that might
             interfere with neuromuscular function.

          -  Any medical condition that may put the subject at increased risk with exposure to
             BOTOX ®including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic
             lateral sclerosis, or known disorders of neuromuscular function

          -  Females who are pregnant, breast-feeding, or planning a pregnancy during the study or
             who think that they may be pregnant at the start of the study, or females of
             childbearing potential who are unable or unwilling to use a reliable form of
             contraception during the study.

          -  Know allergy or sensitivity to any of the components in the study medication.

          -  History of recent or ongoing alcohol or drug abuse.

          -  Known, uncontrolled systemic disease.

          -  Concurrent participation in another research study

          -  Any condition or situation that, in the investigator's opinion, may put the subject at
             significant risk, confound the study results, or interfere significantly with the
             subject's participation in the study.

          -  Patients whose pain is rated as less than 6 on a 10 point Numerical Pain Rating scale
             at the screening visit