Double-Blinded Clinical Trial Using Apatone®B for Symptomatic Postoperative Total Joint Replacements

Study Overview
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Brief Summary
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This research study is being conducted to determine if taking oral (by mouth in pill form) Apatone®B (a combination of Vitamins C and K3) will reduce chronic joint discomfort and improve function of non-infected symptomatic postoperative total joint replacements.

Detailed Description
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To perform a prospective, randomized, double-blind clinical trial to determine if oral Apatone®B, an amalgam of vitamins C and K3, has a therapeutic efficacy beyond the conservative care customarily used to reduce inflammatory synovitis and to increase the functional capacity of proven non-infected symptomatic postoperative total joint replacements.

Official Title
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A Prospective Double-Blinded Clinical Trial Using Apatone®B for Care and Treatment of Proven Non-Infected Symptomatic Postoperative Total Joint Arthroplasties

Conditions
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Edematous, Synovitis, Foreign Body Reaction, Osteolysis

Intervention / Treatment
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* Drug: Placebo
* Drug: Apatone®B


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postoperative Total joint replacement with osteoarthritis as the underlying pathology Proven non-infected symptomatic Total Joint Arthroplasty (TJA) (joint implanted for >12 months post-op) Age (50 to 85 years of age); based on a 10% trim of the age distribution for Summa Health System TJAs (7/1/08-6/30/2009). Exclusion Criteria: An infection of any kind (prior to, or during the study) Rheumatoid arthritis as the underlying pathology Cortisone injection received <6 months prior to study enrollment Insulin dependent diabetes Diagnosed immunodeficiency On dialysis or have poor kidney function Anti-coagulant medication (e.g., Coumadin or >100mg of Aspirin daily) Anti-seizure medication (e.g., Dilantin) Steroidal medication (e.g., Prednisone, Advair or Symbicort) NSAIDS (e.g., Celebrex or Toradol); a 14-day washout period will be allowed bisphosphonates (e.g., Fosamax, Actonel, Aredia, Didronel, Boniva or Reclast) hormonal therapy (e.g., Estrogen, Progesterone or Testosterone) Cancer (active or in remission) Planned concurrent vitamins exceeding a standard daily multivitamin or exceeding the Recommended Daily Allowance (RDA) for individual vitamins if used alone; a 72 hour wash out period will be allowed A glucose-6-phosphate dehydrogenase (G6PD) deficiency Pregnant or lactating; females who are in their reproductive years must have a negative serum pregnancy Lactose intolerant Citric acid intolerant

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: oral Apatone®B<br>An amalgam of Vitamins C & K3 | Drug: Apatone®B<br>* Two capsules taken twice daily with meals<br>|
| Placebo Comparator: Placebo<br>Oral capsule of similar appearance and taste without Apatone®B | Drug: Placebo<br>* Two capsules taken twice daily with meals<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Visual Analog Scale (VAS) | Pain Visual Analog Scale (VAS) Scale range (0-100) A higher VAS score indicate worse knee pain | 13-weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Surrogate Endpoint Markers (SEBs) | HSS = Hospital for Special Surgery Knee Score , KSS = Knee Society Knee Score. Scale range HSS total: 100-90 Excellent; 80-89 Very Good; 70-79 Good; 60-69 Fair; below 60 Poor Scale range HSS pain walking: No Pain 15; Mild Pain 10; Moderate Pain 5; Severe Pain 0 (**this is an element of the HSS total) Scale range KSS: 80-100 Excellent; 70-79 Good; 60-69 Fair; below 60 Poor | 13 weeks | 
| TGFBeta Levels | The final synovial aspirates obtained from the symptomatic knee of each subject were analyzed using Quantikine and Pyrilinks-D enzyme-linked immunosorbent assay kits from R&D Systems (Minneapolis, MN) and Metra Biosystems (Mountain View, CA), respectively. Lower TGFBeta concentrations represent a better outcome. | Baseline and 13 Weeks | 
| Deoxypyridinoline Levels | The final synovial aspirates obtained from the symptomatic knee of each subject were analyzed using Quantikine and Pyrlinks-D enzyme-linked immunosorbent assay kits from R&D Systems(minneapolis, MN) and Metra Biosystems (Mountain View, CA) respectively. Lower DPD concentrations represent a better outcome | Baseline and 13 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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total joint arthroplasty, synovitis, ALVAL (Aseptic Lymphocyte-Dominant Vasculitis-Associated Lesion), osteolysis, periprosthetic metallosis