Trial Evaluating multimOdal toPical Cream In CompArison to pLacebo (TOPICAL)

Study Overview
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Brief Summary
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Randomized controlled trial regarding the efficacy of a multimodal topical analgesic, Multiprofen, in comparison to placebo cream treatment on knee pain and function in patients with knee osteoarthritis.

Detailed Description
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Knee osteoarthritis (OA) is a disease with a high global burden, and multiple conservative treatment options are available. In addition to being a major source of disability osteoarthritis results in a significant economic burden as well. A study published in 2012 showed the 1-year physician, outpatient procedure, and hospitalization costs in patients with osteoarthritis more than double those patients without osteoarthritis in Ontario. Conservative treatment options include topical and oral anti-inflammatory medications, weight loss, physiotherapy and intra articular cortisone and viscosupplementation injections. Unfortunately, commonly used treatments such as oral anti-inflammatory medications carry a significant systemic adverse effect on the gastrointestinal (GI) tract and hepatic and renal systems and intra articular cortisone have potential adverse effect on blood glucose control. For this reason, topical anti-inflammatory medications are popular yet are often ineffective. Unfortunately, topical anti-inflammatory medications have variable efficacy in relieving osteoarthritic knee pain and often only provide a moderate degree of pain relief. In the setting of chronic pain various other topical modalities have been utilized. A systematic review of the literature identified commonly studied topical analgesics were nonsteroidal anti-inflammatory drugs followed by lidocaine, capsaicin, amitriptyline, glyceryl trinitrate, opioids, menthol, pimecrolimus, and phenytoin. Given the biological bases behind utilizing agents which target a variety of pain generators the investigators hypothesized that a combination of these would provide significant pain relief to patients affected by end stage knee osteoarthritis. For this reason, the investigators propose a trial evaluating utilizing multiple topical modalities for pain relief to provide support for the use of combination therapy in treating knee osteoarthritis. Results from this study will potentially improve the global health and economic burden through improvement in the management of knee osteoarthritis. STUDY OBJECTIVES Primary objective The primary objective of the trial will be to evaluate the efficacy of a multimodal topical analgesic, Multiprofen, in comparison to placebo cream treatment on patient reported pain relief utilizing a 11-point visual analog scale (VAS) measured from 0-10. Secondary objectives Our secondary objectives will be to evaluate the effect of topical combination therapy on: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) patient reported outcome score. This score is commonly utilized in assessment of knee osteoarthritis and has been validated to be reliable and responsive in this patient population. Patient knee range of motion and strength Return to previous level of activity Radiographic degree of osteoarthritis. Patient demographics Adverse events SUMMARY OF TRIAL DESIGN The investigators propose a single center blinded trial evaluating the efficacy of a combination formula of topical analgesic in comparison to placebo cream treatment. The investigators will randomize 186 patients between topical multimodal cream multiprofen and a control placebo cream. Randomization Method Participants will be randomized using a random number generator to either experimental or placebo control intervention. Participants will be randomized to one of two treatments: Experimental - A multimodal topical cream treatment with Ketoprofen, Baclofen, Amitryptiline, and lidocaine in a carrier gel. This topical formulation has been in use commercially under the trade name Multi-profen. Control - A identically packaged placebo cream treatment will be utilized in the control population. Proposed duration of treatment and follow-up: Participants will be brought back at 3,6 and 12 weeks' time to complete questionnaires recording VAS and WOMAC scores The current proposal includes 1 clinical site in Canada (Oakville Trafalgar Memorial Hospital, Oakville, ON, CAN)

Official Title
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Trial Evaluating multimOdal toPical Cream In CompArison to pLacebo (TOPICAL)

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Drug: Multiprofen
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The inclusion criteria are: adult men or women ages 50-80 years; Diagnosis of symptomatic osteoarthritis of the knee based on clinical and radiographic criteria; provision of informed consent. Exclusion Criteria: The exclusion criteria are: patients with inflammatory osteoarthritis; open wounds or sores over the knee joint; patients that will likely have problems, in the judgment of the investigators, with maintaining follow-up; Cases involving litigation.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Single center blinded randomized controlled trial with a random number generator determining the allocation of patients to either the placebo or intervention groups.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Multiprofen/interventional<br>A multimodal topical cream treatment with Ketoprofen, Baclofen, Amitryptiline, and lidocaine in a carrier gel. This topical formulation has been in use commercially under the trade name Multi-profen. This topical cream will be applied by the patient three times per day. | Drug: Multiprofen<br>* A multimodal topical cream treatment with Ketoprofen, Baclofen, Amitryptiline, and lidocaine in a carrier gel.<br>|
| Placebo Comparator: Control/Placebo Group<br>A identically packaged placebo cream treatment will be utilized in the control population. | Other: Placebo<br>* An identically packaged placebo cream<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pain visual analog scale (VAS) scores (0-10) from baseline | Measurement of change in patient reported pain score (VAS) at various follow up appointments. The scale is from 0-10, with 10 being the most pain. | week 0, week 3, week 6, week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores from baseline | Change in patient reported knee pain and function scores. WOMAC score has 3 subdivisions which include knee pain, stiffness, and physical function. The score ranges from 0-96, with lower scores representing better knee pain, stiffness, and function. | week 0, week 3, week 6, week 12 | 
| Change in Range of motion (ROM) from baseline | Change in range of motion of the knee at various time points that will be compared to pre-treatment range of motion. Higher range of motion is correlated with better outcome and better function. | week 0, week 3, week 6, week 12 |