Rapid CommunicationsA placebo-controlled trial of ICAM-1 antisense oligonucleotide in the treatment of Crohn's disease☆,☆☆
Section snippets
Study design
The study was a single-center, double-blinded, placebo-controlled, randomized (3:1; ISIS 2302 to placebo), fixed-dose within patient, and dose-escalation trial, approved by the Ethics Committee of the University of Alberta. We enrolled 20 patients between the ages of 18 and 80 who had moderately active Crohn's disease (Crohn's Disease Activity Index [CDAI], 200–350) despite stable background therapy of moderate-dose corticosteroids (prednisone or equivalent, ≤40 mg/day) and mesalamine drugs for
Patients
Baseline characteristics of the ISIS 2302 and placebo patients are shown in Table 1; none of the differences was statistically significant.
Empty Cell ISIS 2302 Placebo No. of patients 15 5 Sex (M/F) 9/6 3/2 Age (yr) 36.5 (18–78) 26.0 (19–33) Disease duration (yr) 8.6 (2–32) 5.7 (2–12) Prednisone dosage (mg/day) 15.5 (10–40) 13.6 (7.5–30) CDAI 294 (201–428) 291 (129–345) EIS 13.05 (1.8–26.1) 8.62 (1.6–17.0) IBDQ 163.9 (93–215) 182 (156–210)
Discussion
This study provided a novel opportunity to use systemically administered antisense in a human disease process, offering us a means to study a very specific manipulation in the treatment of Crohn's disease: the inhibition of ICAM-1 through an antisense mechanism. In addition to following clinical measures, the study was designed to allow an examination of the effects of ISIS 2302 on peripheral blood lymphocyte and intestinal mucosal ICAM-1 expression and the effects of manipulating ICAM-1 on
Acknowledgements
The authors thank Stanley T. Crooke, M.D., Ph.D., for his thoughtful review of the manuscript; Bonnie Wolschuk, R.N., Kim Doan, B.S., and Diana Martini, M.S., for their expert assistance in the execution of the trial; William Pelkey, Ph.D., and Jan Callahan, Ph.D., for the statistical analyses; and Robert A. Rothlein, Ph.D., and Elizabeth Mainolfi, M.S., of Boehringer Ingelheim Pharmaceuticals Inc., for the sICAM-1 analyses.
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Cited by (0)
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Supported by Isis Pharmaceuticals, Inc., Carlsbad, California.
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Address requests for reprints to: Bruce R. Yacyshyn, M.D., Department of Gastroenterology, 2E3.11 Walter MacKenzie Health Sciences Centre, University of Alberta, Edmonton, Alberta, Canada T6G 2R7. Fax: (403) 492-2504.