Knee Pain Clinical Trial
Official title:
Botulinum Toxin A for Painful Total Knee Arthroplasty (TKA): Randomized, Controlled, Triple-blind Study
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.
"This 6-month randomized, placebo-controlled, double blind trial will compare a single
intra-articular (IA) injection of 100 units of Botulinum Toxin A (BoNT/A) to placebo for
improvement in pain, function and quality of life (QOL), and safety in patients with painful
total knee arthroplasty (TKA). Patients will be recruited at the Minneapolis VA Medical
Center. Patients will be eligible if they are over age 18, have TKA, have pain ≥6/10 on 0-10
numeric rating scale (NRS) and are not candidates for revision surgery.
The primary outcome is: (1) proportion with clinically meaningful change in pain severity (on
0-10 scale) 2 months after IA injection. The choice of 2-month for primary end-point is based
on previous observations from open-label case series in painful TKA. Secondary outcomes will
be assessed at each efficacy follow-up (FU) visit. The duration of the trial is 6-months to
capture the duration of pain relief. Based on other trials of Botulinum toxin, we expect the
peak effect between 2-8 weeks and expect the effect to wear off between 2-4 months.
Therefore, for all analyses except duration of pain relief, the efficacy time-points (2 wk, 4
wk, 2 month) and possibly 3- or 4-month (depending on duration of pain relief) will be used.
Secondary outcomes include: (1) clinically meaningful pain relief (≥2-point or ≥30% decrease)
in pain severity (0-10 scale); (2) change in pain severity at 2 months and at all efficacy
time-points; (3) percent with Minimal Clinically Important Improvement on Western Ontario
MacMaster Arthritis Index (WOMAC) pain and function sub-scales at 2 months and at all
efficacy time-points; (4) amount and duration of pain relief; (5) patient and physician
global assessment of response at 2 months and at all efficacy time-points; (6) QOL assessed
by WOMAC and Short-form 36 (SF-36) scores at 2 months and at all efficacy time-points; (7)
change in function by Timed Stands Test (TST) and Timed-up-and-go (TUG) tests at 2 months and
at all efficacy time-points; (8) change in dose of analgesics during the study. We will
determine time to onset of and duration of pain relief and time to improvement in function.
Safety will be assessed by structured interview form for adverse effects, sensory and manual
muscle strength testing, and index joint examination for swelling, erythema and tenderness.
At visit #1, after informed consent and screening for inclusion/exclusion criteria, patients
will undergo: index joint X-ray, laboratory tests; history, physical examination, index joint
pain history, comorbidity and medication history; patient pain assessments, WOMAC and SF-36;
and blinded index joint, neurological examination, TST and TUG tests. 50 patients will be
randomized to receive either IA BoNT/A 100 units or sterile saline in the index joint. FU
phone interviews at 2 and 4-weeks will include pain assessments, WOMAC, patients' global
assessment and adverse effects. Interim visits at 2, 3 and 4-months will be identical to
visit #1, but will also include patients' and physicians' global assessment and there will be
no joint injection. End of study visit at 6 months will be identical to interim visits with
the addition of index joint X-ray and laboratory tests.
Main analyses will include patients with unilateral TKAs. Sensitivity analyses will be done
by including patients with bilateral knees, accounting for correlatedness of observations.
Multiple analysis of variance, mixed model regression analyses and/or generalized estimating
equations will be used for analysis of continuous and categorical outcomes respectively.
Chi-square tests will be used to compare frequency of adverse events. Analysis will be
intention-to-treat.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT02873143 -
5 Year Follow-up of Adolescents With Knee Pain
|
N/A | |
Completed |
NCT00752765 -
The Effects of Bariatric Surgery Weight Loss on Knee Pain in Patients With Osteoarthritis of the Knee
|
N/A | |
Recruiting |
NCT05674604 -
Cryoneurolysis for Knee and Shoulder Pain in an Inpatient Setting
|
||
Terminated |
NCT03171168 -
The Effect of AposTherapy on Knee Pain
|
N/A | |
Completed |
NCT05221047 -
A Reliability and Validity Study of Urdu Version of Knee Outcome Survey-Activities of Daily Living Scale
|
||
Terminated |
NCT01351558 -
Exercise and Pain Sensitivity
|
N/A | |
Terminated |
NCT00601341 -
Effects of Lumbosacral Joint Mobilization/Manipulation on Lower Extremity Muscle Neuromuscular Response
|
N/A | |
Completed |
NCT03969654 -
ROSA Robot Used in Total Knee Replacement Post Market Study
|
N/A | |
Completed |
NCT03910036 -
Effect of PRP Injection After Arthroscopic Meniscal Repair in the Healing Process
|
Phase 4 | |
Terminated |
NCT01764139 -
Vitamin D Levels In Patients Who Has Normal to Grade 2 Knee Arthroscopy Changes
|
N/A | |
Withdrawn |
NCT01112319 -
The Effects of the Electro, Heat and Cold -Therapy During Physiotherapy Treatment in Osteoarthritis(OA) of KNEE
|
Phase 1 | |
Completed |
NCT00662493 -
A Comparison of Two Exercise Programs on Knee Motor Control
|
Phase 2 | |
Completed |
NCT03956875 -
Yoga for Aromatase Inhibitor-related Knee Pain Relief in Breast Cancer Patients
|
N/A | |
Completed |
NCT03072108 -
Dietary Supplement for Joint: the OLE Study
|
N/A | |
Completed |
NCT00923598 -
Optimizing Local Anesthetic Concentration for Continuous Femoral Nerve Blocks
|
Phase 4 | |
Terminated |
NCT03970629 -
ROSA Total Knee Investigational Testing Authorization Study
|
N/A | |
Completed |
NCT00745069 -
Efficacy and Safety of Tapentadol Extended Release Tablets in the Treatment of Moderate to Severe Pain in Subjects With Knee Osteoarthritis
|
Phase 2 | |
Completed |
NCT03815448 -
Methotrexate in the Treatment of Advanced Knee Osteoarthritis With Effusion-synovitis
|
N/A | |
Recruiting |
NCT04084236 -
The Effects of Transcutaneous Electrical Nerve Stimulation on People With Knee Osteoarthritis (OA) and or Chronic Pain
|
N/A | |
Completed |
NCT05470244 -
TENS in Post-operative Total Knee Arthroplasty Recovery and Intra-venous Analgesics Requirement
|
N/A |