Clinical Trials

As part of the mission of the Rush Cartilage Restoration Center, orthopaedic surgeons at Rush are committed to providing patients with the full range of contemporary treatment options, including the latest minimally invasive procedures. Below is a brief description of a variety of ongoing research studies. If you would like more information about them, you can feel free to call the office or inquire about them at your next visit. All research studies have been approved by the Institutional Review Board at Rush-Presbyterian-St. Luke's Medical Center. Involvement in any fashion is purely elective and patients will undergo a thorough informed consent process. Patient information is strictly confidential and will only be used for research purposes.

Cole Research Summary 2008
Summary of Ongoing Research Efforts
The Cartilage Restoration Center Core Laboratory and Clinical Research Program

Knee

The Cartilage Restoration Center at Rush University Medical Center, under the Direction of Dr. Brian J. Cole, is in its 14th year. Over the last decade, we have collected data and reported on more than 1,000 transplants and cartilage repair procedures. These publications and the rehabilitation protocols that you might find helpful for your practice are available in the Resource Library.

Below is a brief description of our ongoing clinical trials as they relate to the knee. If you believe you or your patients might qualify for these clinical trials or wish to have evaluated, please contact our research administrator, Mukesh Ahuja at 312-563-2214 or mahuja@rushortho.com. As always, I will make myself available at bcole@rushortho.com.

Cartilage Restoration

Prospective Studies: For patients scheduled to have one of the following procedures, we encourage you to participate in regularly scheduled follow-up visits (6-month, 1-year, 2-year, 3-year). Your progress will be carefully monitored through self-assessment and physical examination. Many of these procedures are relatively new, and prospective studies may contribute to the management of these and other related conditions.

• Autologous chondrocyte implantation (ACI)
• Osteochondral autograft transplantation
• Osteochondral allograft transplantation
• Meniscus transplantation

CARTILAGE TRIALS AT RUSH

BIOLOGIC IMPLANTS

DENOVO NT
DeNovo® NT (Natural Tissue) is a human tissue allograft consisting of particulated juvenile articular cartilage intended for implantation at the lesion site with the help of fibrin adhesive. Chondrocytes within the DeNovo NT implant clone, divide and produce matrix leading to defect fill and peripheral integration. The Denovo NT Graft is surgically implanted and affixed to subchondral bone using commercial fibrin during a mini-open knee arthrotomy. This is a post market, prospective, non-randomized study to assess the clinical outcomes of DeNovo® NT for the treatment of one or two contained lesion(s) equal to ICRS Grade 3 (Outerbridge Grade III/IV) of the femoral condyle or trochlear groove and OCD lesions with minimal involvement of the subchondral bone. Male and non-pregnant female patients between 18 and 55 years of age are screened for study recruitment. This is a two-year study and clinical evaluations will be performed preoperatively and postoperatively at 2 weeks, 3, 6, 12, 18, and 24 months. Pre- and postoperative radiographs and MRIs will be performed.

DENOVO ET
Denovo ET (Engineered Tissue) Graft is an in vitro grown, 3-dimensional hyaline-like cartilage tissue created by culturing disaggregated allogeneic chondrocytes derived from juvenile human donors. Each implant contains viable cultured chondrocytes embedded in a viscoelastic matrix created entirely by the chondrocytes during in vitro culture. The Denovo ET Graft is surgically implanted and affixed to subchondral bone using commercial fibrin during a mini-open knee arthrotomy. Having completed the pre-clinical work and Phase I study at Rush, the FDA has approved the enrollment for a pivotal Phase III clinical trial. This is a prospective randomized study compared to microfracture. The purpose of this phase III clinical trial is to demonstrate the efficacy and safety of the Denovo ET Implant for the treatment of ICRS Grade 3 to 4 articular cartilage lesions of the knee compared to microfracture treatment.

Male and non-pregnant female patients between 18 and 60 years of age are screened for study recruitment. This is a five-year study and clinical evaluations will be performed preoperatively and postoperatively at 6 weeks, 6, 12, 18, 24, 36 months and annually thereafter through 5 years. Pre- and postoperative radiographs and MRIs will be performed.

CAIS
CAIS (Cartilage Autograft Implantation System) utilizes morselized autologous hyaline cartilage harvested arthroscopically that is affixed onto a synthetic, resorbable implant using a fibrin sealant and implanted in a single-stage procedure through a mini-open knee arthrotomy.

Having completed the pre-clinical work and Phase I study at Rush, the FDA has approved the enrollment for a pivotal Phase III clinical trial. This is a prospective randomized study compared to microfracture for isolated defects of the femur. The purpose of this phase III clinical trial is to demonstrate the efficacy and safety of the CAIS implant for the treatment of non-OCD lesions (between ICRS grades I and IIID) or OCD lesions (between ICRS grades I and IVA) of the knee compared to microfracture treatment.

Male and non-pregnant female patients between 18 and 55 years of age are screened for study recruitment. This is a four-year study and clinical evaluations will be performed preoperatively and postoperatively at 1 & 3 weeks, 3, 6, 12, 18, 24, 30, 36, 42 and 48 months. Pre and postoperative radiographs and MRIs will be performed.

LIMITED RESURFACING IMPLANTS

HEMICAP RESURFACING PROSTHESIS
The HemiCAP™ implant is a limited resurfacing arthroplasty component designed to match the shape and contour of the individual patient's cartilage surface. It is essentially a resurfacing "patch" for an area of damaged cartilage and bone designed to protect the remaining, normal cartilage in an attempt to prevent further damage. The HemiCAP is intended to manage pain and disability in the middle-aged and older patient until a total joint replacement treatment option becomes more necessary and is part of a clinical treatment strategy to avoid early-age-revision scenarios.

This is a prospective, non-randomized, open label pivotal clinical trial to evaluate the safety and efficacy of the HemiCAP Resurfacing Prosthesis for the treatment of focal femoral condyle defects. The clinical indication is limited to those individuals with significant pain and loss of joint function associated with large unstable full thickness articular (ICRS Grade 4) and osteochondral defects who have not responded to other treatments including previous cartilage repair surgery.

Male and non-pregnant female patients between 35 and 60 years of age are screened for study recruitment. This is a two-year study and clinical evaluations will be performed preoperatively and postoperatively at 2 & 6weeks, 3, 6, 12 and 24 months. Pre and postoperative MRIs will be performed.

MENISCUS TRIAL

MENISCAL TEAR WITH OA RESEARCH (MeTeOR)
Significant controversy remains about the short- and long-term benefits of mensicetomy performed in a setting of concomitant arthritis. Rush University Medical Center is part of a multi-center NIH funded study investigating this problem. This is a randomized controlled trial of arthroscopic partial meniscectomy (APM) versus a standardized non-operative management program among patients (age 45 or above) for patients with symptomatic meniscal tear in the setting of concomitant knee osteoarthritis.

The principal goals of the trial are:

1. To establish whether APM is efficacious as compared to a standardized non-operative management program for pain relief and functional improvement in this population six months after treatment initiation.
2. To identify prognostic factors associated with favorable outcomes among patients randomized to APM, and among those randomized to the nonoperative program. To identify types of patients in whom surgery is particularly efficacious (or inefficacious), as compared with nonoperative therapy.

The trial cohort will be followed for two years to examine differences in the efficacy of APM as compared with nonoperative therapy over a longer period of follow-up. Patients will be scheduled for a baseline evaluation, an intervention, and two follow-up evaluations at 3 and 18 months. The total duration of participation will be two years for each patient.

OSTEOARTHRITIS TRIAL

AUTOLOGOUS CONDITIONED PLASMA (ACP) vs. HYALURONIC ACID (HA)
Autologous blood products (i.e., PRP or platelet rich plasma) provide cellular and humeral mediators from platelets which are beneficial in augmenting tissue healing. It has been hypothesized that this response is due to the presence of varying growth factors in platelets favoring anabolic effects and inhibiting catabolic effects associated with oosteoarthritis. The Autologous Conditioned Plasma Double Syringe (ACP-DS) is a double-syringe system, which rapidly isolates platelets and growth factors (GF) from patient’s own peripheral blood.

The purpose of this randomized, double-blind, prospective trial is to investigate the use of ACP in patients with knee osteoarthritis and compare clinical & biological responses of ACP to current standard treatment, Hyaluronic-Acid. Over the course of 36 months, 100 patients will undergo synovial fluid aspiration at the time of injection, subjective questionnaires, physical-examination and imaging at set time-points to determine the effects of each treatment.

Inclusion criteria for this study will include patients between the ages of 18-80 with an image verified diagnosis of OA and symptomatic pain for at least one month with no recent treatment using intra-articular injections of the knee (i.e., corticosteroids or HA). Patients will be scheduled to receive injection once a week for three consecutive weeks and evaluations will be performed at baseline, week 1, 2 & 5 and month 3 & 6. The total duration of participation will be 6 months for each patient.

Platelet-Rich Plasma

Can Platelet-Rich Plasma Ease the Pain of Osteoarthritis?

CHICAGO—For years, doctors have used platelet-rich plasma, or PRP, to promote healing after surgery. Now, Rush University Medical Center is studying whether PRP can help relieve knee pain in patients with mild to moderate osteoarthritis. PRP contains growth factors that promote cell proliferation and is prepared from the patient's own blood tissue. It has received popular attention because of its use in treating sports injuries in professional athletes, but the jury is still out on whether it is effective.

"There have been few controlled clinical trials, and results are inconsistent, but data so far suggests that it could be a promising treatment for healing in a variety of tissues," said Dr. Brian Cole, orthopaedic surgeon and head of the cartilage restoration center at Rush. "The therapy will not be a cure for osteoarthritis, but it could help put off the day when a patient will need to get a knee implant." At present, the standard of care is either corticosteroid injections, which may last about three months, or synthetic lubricants containing hyaluronic acid, which can last for up to a year.

In the double-blind, randomized, controlled study, 100 patients will receive either hyaluronic acid or PRP. The PRP is prepared from 10 millimeters of the patient's own blood. The blood is spun in a centrifuge to separate the platelets from the red and white blood cells. The platelets are then injected into the knee joint using ultrasound imaging to guide placement.

Patients will receive three injections over three weeks, and will be monitored for two years receiving a clinical exam to assess pain and knee function. In addition, a teaspoon-size sample will be taken of the synovial fluid around the knee joint to test for molecular changes that may indicate a shift in the balance of anabolic factors that increase the buildup of tissue and catabolic factors that break it down. An imbalance in these factors has been implicated in the deterioration that leads to osteoarthritis.

For additional information, please contact the study's research coordinator Vasil Karas (312.432.2380 or email vasili.karas@gmail.com) or Dr. Brain Cole at bcole@rushortho.com.

Shoulder

Arthroscopic Rotator Cuff Repair

Prospective Study: For patients scheduled to have arthroscopic rotator cuff repairs, we encourage you to participate in regularly scheduled follow-up visits (6-month, 1-year, 2-year, 3-year). Your progress will be carefully monitored through self-assessment and physical examination. This procedure is relatively new, and the prospective studies may contribute to the management of this and related conditions.

Normal Shoulder Function: A survey is performed that includes subjective and objective data to quantify shoulder function. We believe that there are a few variables that may influence the outcome of the score, namely age, sex, and hand dominance. We are currently collecting data from patients with normal shoulders to create a database sufficient to describe normal shoulder function to better understand disease processes.