Clinical Trials and IBD

Since 1996, our centre has participated in many national and international clinical drug trials for IBD. We have several ongoing trials, and these are detailed below, or click here.

The most recent drugs to come to the Canadian market are Remicade (Infliximab), which is used in patients with Crohn’s disease and rheumatoid arthritis, and Humira (adalibumab) for Crohn’s disease. More information on these drugs is available by clicking here

In order for a new drug to become commercially available, the pharmaceutical companies must apply to the regulatory agencies such as the FDA in the US and Health Canada for permission to conduct their research on human subjects. The research process follows strict clinical and governmental guidelines, and once approved it must be reviewed and approved by the local Research Ethics Board before any subjects are recruited. Subjects are recruited into clinical drug trials in a variety of ways, including directly from the physician’s clinic or upon referral from another physician or through advertisement such as in the local paper. All subjects enter into a clinical drug trial voluntarily and may withdraw their participation at any time. There are at least 4 Phases in the clinical drug trial process.

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The Phase II and Phase III studies are most common in our research centre. The clinical drug trials randomly assign the chance to receive either the active substance or an inactive substance, called a placebo. The decision as to who receives study drug or not is done by computer in most cases, and no one at the research site knows whether the subject is assigned to study drug or placebo. If necessary, the physician has the ability to find out which substance the patient is taking after contacting the pharmaceutical medical monitor. Placebo continues to be a part of clinical trials in IBD because remarkably approximately 30% of subjects receiving placebo will improve. Clinical drug trials can be as short as 12 weeks or as long as 60 months. Participation in a clinical drug trial means committing your time and energy to the study, and complying with the study visits. The advantage to participating in a clinical trial is that drug is provided free of charge, and these trials allow patients potential access to new and hopefully safer drugs. A disadvantage of participating is that you need to speak with or see our study nurses often. Some may think this is an advantage! It also means that participants must take an active role in their care. During and after the study has been completed, the research staff are watching for side effects and monitoring the effectiveness of the study drug on the participants. The research office is notified of any potentially harmful effects that might be discovered during the clinical drug trial, and these are communicated to the participants. If all goes well and the pharmaceutical company can prove that their drug works well in those diseases that it is intended for, then the government agencies will approve the drug for use in the general public.

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Recent clinical trials published that our Centre participated in

Buchman AL, Katz S, Fang JC, Bernstein CN, Abou-Assi SG; for the Teduglutide Study. Teduglutide, a novel mucosally active analog of glucagon-like peptide-2 (GLP-2) for the treatment of moderate to severe Crohn’s disease. Inflammatory Bowel Diseases 2010: 16; 962-973

Teduglutide, an analog of glucagon-like peptide-2 (GLP-2), is associated with trophic effects on gut mucosa (this means that it can enhance growth and development of the lining of the bowel). Its role in the treatment of active Crohn’s disease was assessed in a pilot, randomized, placebo-controlled, double-blinded, dose-ranging study. Persons with moderate-to-severe Crohn’s disease received 1 of 3 doses of teduglutide (0.05, 0.10, or 0.20 mg/kg daily) delivered as a daily subcutaneous injection for 8 weeks or placebo. The primary outcome measure was the percentage of subjects in each group that responded to treatment, defined as a decrease in Crohn’s Disease Activity Index (CDAI) score to <150 or a decrease of > 100 points. At week 8 there was an optional 12-week open-label period of treatment with teduglutide 0.10 mg/kg/d. Overall 100 persons were enrolled and 71 completed the study. There were numerically higher response and remission rates in all teduglutide-treated groups as compared with placebo, although the percentage of subjects who achieved a clinical response or remission was more substantial, and seen as early as week 2 of treatment in the highest dose (0.2 mg/kg/d) group (44% response and 32% remission versus 32% response and 20% remission in the placebo group). Of persons who had not achieved remission during the 8-week placebo-controlled phase in the higher-dose group, 50% achieved remission during the more prolonged, open-label treatment phase.. Adverse events were not different between placebo and active treatment groups. We concluded that Teduglutide is a novel and potentially effective therapy for inducing remission and mucosal healing in patients with active moderate-to-severe Crohn’s disease. Further clinical investigation of this growth factor is warranted.

Thia KT, Mahadevan U, Feagan BG, Wong C, Cockeram A, Bitton A, Bernstein CN, Sandborn WJ. Ciprofloxacin or metronidazole for the treatment of perianal fistulas in patients with Crohn’s disease: A randomized double-blind, placebo-controlled pilot study. Inflammatory Bowel Diseases 2009; 15: 17-24.

This study could not be fully completed because of failure to enroll sufficient patients and hence this serves as a pilot study. This is unfortunate because there are no studies that clearly prove the efficacy of antibiotics to treat perineal fistulas in Crohn’s disease. Nonetheless, they do seem to have some efficacy and hence metronidazole (Flagyl) and ciprofloxacin remain mainstays as therapy of perineal fistulas.

Reinisch W, de Villiers W, Bene L, Simon L, Rácz I, Katz S, Altorjay I, Feagan B, Riff D, Bernstein CN, Hommes D, Rutgeerts P, Cortot A, Cheng M, Pearce T, Sands B. Fontolizumab in Moderate to Severe Crohn’s Disease: A Phase 2, Randomized, Double blind, Placebo-controlled, Multiple-dose Study. Inflammatory Bowel Diseases 2009; 16: 233-42.

Fontolizumab, is an antibody to interferon gamma which like TNF is a proinflammatory protein we all make in our bowels and elsewhere in our body. Use of this antibody was studied in patients with Crohn’s disease (CD). A total of 201 patients with Crohn’s Disease were enrolled in this study. The drug did not clearly show benefit in Crohn’s disease activity compared to placebo, although the drug appeared to be safe. It is unclear if further studies will be conducted with these agents.

Other clinical trials now published that our Centre participated in

Schreiber S, Feagan B, D’Haens G, Colombel JF, Geboes K, Yurcov M, Isakov V, Golovenko O, Bernstein CN, Ludwig D, Winter T, Meier U, Yong C, Steffgen J for the BIRB 796 Study Group. Oral p38 mitogen activated protein kinase (MAPK) inhibition with BIRB 796 for active Crohn’s disease: a randomized, double-blind, placebo-controlled trial. Clinical Gastroenterology and Hepatology 2006; 4:325-34

Schreiber S, Rutgeerts P, Fedorak RN, Khaliq-Kareemi M, Kamm MA, Boivin M, Bernstein CN, Staun M, Thomsen OO, Innes A; CDP870 Crohn’s Disease Study Group. A randomized, placebo-controlled trial of Certolizumab Pegol (CDP870) for treatment of Crohn’s Disease. Gastroenterology. 2005;129: 807-818.

Feagan BG, Sandborn WJ, Baker JP, Cominelli F, Sutherland LR, Elson CO, Salzberg BA, Archambault A, Bernstein CN, Lichtenstein GR, Heath PK, Cameron S, Hanauer SB. A randomized, double-blind, placebo-controlled trial of CDP571, a humanized monoclonal antibody to tumor necrosis factor-a, in patients with corticosteroid-dependent Crohn’s disease. Alimentary Pharmacology and Therapeutics 2005; 21: 373-84.

Sands BE, Anderson FH, Bernstein CN, Chey W, Feagan BG, Fedorak RN, Kamm M, Korzenik JR, Lashner BA, Onken J, Rachmilewitz D, Rutgeerts P, Wild G, Wolf DC, Marsters PA, Travers SB, Blank MA, van Deventer SJ. Infliximab Maintenance Therapy for Fistulizing Crohn’s Disease (ACCENT II). New England Journal of Medicine 2004;350: 876-85.

Thia KT, Mahadevan U, Feagan BG, Wong C, Cockeram A, Bitton A, Bernstein CN, Sandborn WJ. Ciprofloxacin or metronidazole for the treatment of perianal fistulas in patients with Crohn’s disease: A randomized double-blind, placebo-controlled pilot study. Inflammatory Bowel Diseases 2009; 15: 17-24.

 

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