Summer 2006

Massachusetts General Hospital Physicians Test Leukocytapheresis Device for Treatment of Ulcerative Colitis and Crohn’s Disease

The Massachusetts General Hospital Crohn's and Colitis Center is conducting two multi-center double-blinded sham-controlled clinical trials of a device that may help reduce the signs and symptoms of ulcerative colitis (UC) and Crohn's disease (CD).

Bruce E. Sands, MD, Medical Co-director of the Crohn's and Colitis Center and international principal investigator for both trials, says, "Medical therapy - antiinflammatory drugs, immunosuppressants, and biologics - is effective in reducing symptoms and achieving remission in some patients, but other patients either do not respond to or cannot tolerate standard pharmacologic therapy. Leukocytapheresis is the first nonpharmacologic approach to treating UC and CD to be tested in the U.S. This approach seems to be appealing to patients because it does not introduce a medication and its potential side effects into the body, but rather removes activated cells that may have a role in the disease process." Appropriate candidates for both trials have moderate to severe disease that does not respond adequately to standard medications. The protocol regimen consists of ten selective apheresis treatments using the Adacolumn Apheresis System, a unique leukocytapheresis device that selectively adsorbs granulocytes and monocytes. The system consists of a column filled with cellulose acetate beads that trap the granulocytes and monocytes, a blood pump and associated monitors, and a venous access system.

Each treatment lasts approximately one hour with a flow rate of approximately 30 ml/minute. Less than one-third of the total circulation passes extracorporeally through the column, and about 50 percent of the granulocytes and monocytes in that volume are removed. Disease activity is monitored at regular intervals throughout the treatment period using the disease activity index (DAI) for UC patients and the Crohn's disease activity index for CD patients. The primary endpoint is response at twelve weeks. Definitions of response and remission are consistent with current FDA standards.

The UC trial is closed, but researchers are still actively recruiting appropriate candidates for the CD trial who may benefit from this therapy. The current trials are based on results of earlier uncontrolled trials in Japan and Europe, as well as a pilot feasibility study, of which Dr. Sands was principal investigator, that evaluated the safety, tolerability, and efficacy of selective apheresis to treat symptoms of UC and CD.

That study, currently in press at the Journal of Clinical Gastroenterology, suggested that the procedure is safe and generally well tolerated. Side effects - mainly headache, dizziness, and nausea - are common to all apheresis procedures and were tolerable and transient. Researchers did conclude that adequate venous access is critical to patient comfort and acceptance of the procedure.

The findings also suggested that the procedure is feasible in a range of settings, including academic medical centers and private practice clinics, and that it appears to have an effect on disease activity.

The mechanism by which selective apheresis achieves a therapeutic effect is not yet entirely clear. Activated granulocytes and macrophages are found abundantly in the intestinal mucosa of inflammatory bowel disease sufferers, and removal of these cell populations involved in perpetuating inflammation seems likely to be responsible for some of the effect. However, when blood is run extracorporeally, there are effects on the cells, and these may also contribute to an anti-inflammatory effect.

Dr. Sands concludes, "Assuming we are able demonstrate that Adacolumn leukocytapheresis is superior to the sham treatment in achieving response and remission in patients with active disease, questions about how best to use the system remain. Further trials will seek to elucidate whether it is possible to give cycles of therapy to prevent relapse, and if so, what is the optimum timing."

Crohn's and Colitis Center Clinical Trials

1. Prospective registry in IBD study at Massachusetts General Hospital (PRISM).
2. Double-blind, randomized, parallel arm, dose ranging study of IMURAN in subjects with active Crohn's Disease requiring treatment with Prednisone: A Crohn's Disease Optimal Range Dose of IMURAN Study (ACORDIS).
3. Probiotics and Intestinal Disease: The effect of Probiotics on fecal flora and symptoms of patients with Crohn's Disease.
4. A study of pouch outcomes among patients who have undergone Restorative Proctocolectomy with Ileal Pouch Anal Anastomosis.
5. A prospective, randomized, double-blinded, placebo (Sham) controlled study to evaluate the safety and efectiveness of the Adacolumn Apheresis System for the treatment of moderate to severe Crohn's Disease.