Safety and Efficacy of Botulinum Toxin A Injection in Patients With Painful Artificial Knee Arthroplasty (TKA)

NCT00403273 | Completed Phase 2 Results

• 1 other identifier: 1-singh
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Knee Pain

Keywords

Painful Knee Arthroplasty; Botulinum Toxin A; Randomized Controlled Trial; Pain and Function

Outcome Measures

Primary Outcomes (1)

• Participants With Clinically Meaningful Improvement in Pain Severity (0-10 cm; Higher Score on Pain Scale is Worse)

  2-point reduction in pain Visual Analog Scale (VAS) from baseline to the 2-month follow-up visit, which is considered clinically meaningful Change in Pain Severity; Pain Severity on VAS ranges from 0 (no pain) to 10 (maximum pain)

  2-month post-injection

Secondary Outcomes (16)

• Mean Pain VAS (0-10)

  2-months post-injection

• Physician Global Assessment of Response to Treatment

  2-month (primary end-point)

• Physical Function Subscale of the WOMAC at 2-months

  2-month

• WOMAC Stiffness (0-100)

  2-months

• Timed Up-and-go (TUG) Test

  2-month

Study Arms (2)

A

EXPERIMENTAL

Single Intra-articular Injection of 100 units of Botulinum toxin A in 5 cc of normal saline in the Painful TKA at screening visit

Drug: Botulinum toxin A

B

PLACEBO COMPARATOR

Single Intra-articular Injection of 5 cc of normal saline in the Painful TKA at screening visit

Drug: Normal Saline

Interventions

Botulinum toxin A DRUG

100 units of Botulinum toxin A in 5 cc of normal saline in the Painful TKA at screening visit

Also known as: Botox

A

Normal Saline DRUG

Single Intra-articular Injection of 5 cc of normal saline in the Painful TKA at screening visit

Also known as: saline control

B

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Minneapolis Veterans Affairs Medical Center: lead
• University of Minnesota: collaborator
• Arthritis Foundation: collaborator

Study Sites (1)

Minneapolis VA Medical Center

Minneapolis, Minnesota, 55417, United States

Location

Related Publications (1)

• Singh JA, Mahowald ML, Noorbaloochi S. Intraarticular botulinum toxin A for refractory painful total knee arthroplasty: a randomized controlled trial. J Rheumatol. 2010 Nov;37(11):2377-86. doi: 10.3899/jrheum.100336. Epub 2010 Sep 1.

  PMID: 20810509 RESULT

MeSH Terms

Conditions

Pain

Interventions

Botulinum Toxins, Type A; Saline Solution

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: jasvinder singh
• Organization: minneapolis VAMC

205-504-9559

Study Officials

• Jasvinder Singh, MBBS, MPH

  Minneapolis Veterans Affairs Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: worker without compensation

Study Record Dates

• First Submitted: November 21, 2006
• First Posted: November 23, 2006
• Study Start: July 1, 2006
• Primary Completion: January 1, 2009
• Study Completion: January 1, 2009
• Last Updated: May 21, 2018
• Results First Posted: November 18, 2016

Record last verified: 2018-04

Locations

US (1)