Trial of Realignment Therapy for Treatment of Medial Knee Osteoarthritis

We propose a double blind, randomized crossover trial of a realignment therapy for patients with medial knee osteoarthritis with the primary outcome being knee pain and function as assessed by the WOMAC Osteoarthritis Index (VAS Version). Because of the possibility that the therapy may provide proprioceptive input and improve symptoms on that basis, we will test two different treatments: 1. CONTROL TREATMENT A) a neutral brace that does not have any varus/valgus angulation, control foot orthotic and shoes with flexible midsole and 2. ACTIVE TREATMENT B) an valgus brace, customized functional orthotic for neutral foot position and motion control footwear. A run-in design will be used to maximize the likelihood of recruiting subjects who will remain in the trial. Subjects will be randomized to treatment A or B for 12 weeks. We will then remove the realignment therapy of treatment period 1, and they will have no realignment therapy for 6 weeks, after which they will receive the other treatment. For each subject, the trial will last 34 weeks. Study evaluation will take place at the Boston University Medical Center GCRC. The trial will be followed by a 6-month open-label follow up. Trial Schedule. We plan a study lasting a total of 30 weeks from the time of randomization for all subjects. There will be 4 weeks pre-randomization for run-in; a phone call at -4weeks and a visit at -2 weeks. The schedule of visits is shown in the protocol as is the timeline. Intervention The active treatment brace will be the DonJoy OA valgus brace. The active treatment orthosis will consist of a customized functional orthosis to achieve neutral foot position. The active treatment shoewear will be a motion control shoe with an appropriate (based upon foot posture examination) density midsole and heel counter. The control treatment brace will consist of an identical brace with a loosened screw at the hinge allowing varus-valgus laxity. The control treatment orthosis will be flat 1/8" thick inserts of an identical material to the active treatment arm. The control treatment shoe will be identical in appearance with a low density midsole to limit motion control. Treatment shoes will be worn on both feet during each treatment period. Recruitment One key element ensuring success in recruitment for the proposed clinical trial for osteoarthritis is experience with and history of success in recruitment for previous studies. We have successfully recruited targeted number of subjects for 2 recent OA clinical trials and a natural history study of OA all of which have more subjects than are targeted here. We are currently completing an NIH-funded heel wedge study which uses a similar design and study population to the one being employed here and both the clinical trial experience obtained, and the continuing recruitment for that study will facilitate recruitment for this trial. The efficacy of a clinical trial is maximized if subjects comply with assigned treatment and come to scheduled visits. One way to increase the likelihood of subject compliance with a trial is to perform a run-in test, a period of observation prior to randomization during which subjects get experience with major components of the study protocol. Those subjects who have trouble complying with the protocol are excluded before being randomized. Despite the exclusion of potential subjects, trial run-ins have been shown to enhance a trial's statistical power by limiting its results to those who were especially likely to actually receive treatment. A recent test of a run-in in an osteoarthritis trial reported that roughly 10% failed a 4-week run-in and that the exclusion of these subjects from the trial increased efficiency and lowered the number of subjects needed and was highly beneficial. We propose a run in period in which there will be a screening phone call, a visit two weeks later (prerandomization visit), with the randomization visit 2 weeks after the initial visit. This will be a placebo run-in with administration of the control shoe and orthotic for this 2-week period. The run in serves several purposes in addition to the efficiency and adherence reasons noted above. It permits us to obtain radiographs, assess and custom manufacture knee brace, orthotics and shoewear, and review them prior to randomization. It also allows us to assess pain status twice so as to get an average of knee pain scores prior to the trial. One concern of a run-in is that it may limit generalizability by excluding some subjects who fail the run-in test. In this trial we will be assessing efficacy so we need to maximize internal validity. Moreover losing subjects in crossover trial is a major concern and we would like to minimize this. We will preserve allocation concealment by having the randomization codes held by the Data Coordinating Center at Boston University, School of Public Health that is external to the Clinical Epidemiology and Research Training Unit. We will stratify patients into those with end stage (Kellgren & Lawrence Grade 4-specifically bone on bone in the weight bearing knee film in the medial compartment) versus those with disease that is moderate or mild yet still affecting the medial joint. We will then perform blocked stratified randomization ensuring that we randomize roughly equal numbers of patients with severe disease and those with mild to moderate diseases into each of the two treatment arms. We will incorporate a blocked randomization scheme so as to permit roughly equal numbers of subjects to be randomized to each treatment within each of the strata of interest. Blinding We will attempt to conduct a blinded trial. Ideally, a blinded trial presents identical appearing treatments to the patients, and obviously, we cannot accomplish this. Nonetheless, our description of the treatments to the patients will be that we will be comparing two types of treatment for their knee arthritis without specifying which therapy constitutes active treatment. The physician responsible for observations during the study visits will also be blind to subject interventions during each phase. Outcomes to be assessed -Primary Outcome -WOMAC Pain and Function Subscales (Most symptomatic treated Knee) -Secondary Outcomes WOMAC Stiffness Subscale Knee Injury and Osteoarthritis Outcome Score Patient Global Assessment Overall Knee Pain V.A.S. (Knee specific) SF36 Analgesic Use (Medication log) Blinded knee exam by physician Physician Global Assessment Functional performance measures (timed gait and chair stand) Gait analysis (see further description below) Knee malalignment (Measured from long limb films) Proprioception (Ability to reproduce passive positioning of the knee). Open Label Follow-up At the end of their participation in the trial, subjects will be allowed to keep the therapy they used. We will ask them which therapy helped them most, and we will strongly encourage continued use. We will continue to follow these subjects for an additional 6 months. We will schedule open label study follow-up visits at 2, 4 and 6 months during which subjects' realignment therapy will be re-examined. Replacements will be provided if necessary. We will also administer the WOMAC at these visits to asses whether treatment effects remain. At these visits, subjects will be queried about adherence; whether they continue to use the realignment therapy, how many days per week (from an adherence diary) they have worn them. This data will enable an assessment of long term adherence, and also enable us to ascertain if response is contingent on adherence. During all phases of the study participation, subjects will receive educational materials that have been approved by the IRB either during their visits or via the mail. These are intended to keep subjects engaged and thereby help with retention in the study.