G-CSF to Treat Crohn's Disease
This study will examine the effectiveness of G-CSF in treating patients with Crohn's disease-a long-term recurring inflammation of the small and large intestine. Patients may have swelling and bleeding of the intestinal lining, which can lead to infection and abdominal pain, weight loss, fever, diarrhea, bloody stools, fistula (connections between the skin and intestine), intestinal blockages, and abscesses. Although there are various treatments for Crohn's disease, many patients continue to have inflammation that is difficult to control or severe side effects from the medications. G-CSF is an approved drug that is used to increase white blood cell counts. Other cells, immune cells, exposed to G-CSF can develop a specific immune action-a Th-2 response-that decreases the inflammatory response in Crohn's disease-a Th-1 response.
Patients 18 years of age or older who have had mild to moderately severe Crohn's disease for at least 4 months may be eligible for this study. Candidates will be screened with a medical history and possible review of medical records, physical examination, blood tests, electrocardiogram (EKG), urine and stool analyses and, for women, a pregnancy test. They will fill out a Crohn's Disease Activity Index questionnaire daily for 7 days and an Inflammatory Bowel Disease questionnaire.
Participants will have G-CSF therapy. Before starting therapy, they will have a series of pre-treatment tests, including a colonoscopy and leukapheresis. Colonoscopy is an examination of the colon. For the procedure, patients are given a medication to lessen anxiety and any discomfort. An endoscope-a lighted flexible tube-is inserted into the rectum, allowing examination of the extent of inflammation. The endoscope can also be used to take pictures of the colon and extract tissue samples for testing (biopsy). Leukapheresis is a procedure for collecting quantities of white blood cells. Whole blood is collected through a needle placed in an arm vein and circulated through a machine that separates it into its components. The white cells are removed, and the rest of the blood is returned to the body, either through the same needle used to draw the blood or through another needle placed in the other arm.
After the colonoscopy and leukapheresis, patients receive G-CSF injections every day for 29 days. The patient or a caregiver, such as a family member, will be taught to give the injections. Blood samples will be collected on treatment days 4, 8, 11 and 15, and a physical examination and interview, blood tests and a stool exam will be done once a week. Patients will have a repeat colonoscopy and leukapheresis 24 hours after the last treatment dose (day 29).
After the 29-day treatment, patients will be followed in the clinic as follows:
- Week 4 after treatment - physical exam and interview, routine blood work and stool exam
- Week 8 - interview and blood work
- Week 16 - interview, blood work and stool exam
- Week 24 - physical exam and interview, blood work, stool exam and colonoscopy
|Study Design:||Primary Purpose: Treatment|
|Official Title:||Granulocyte-Colony Stimulating Factor Treatment for Crohn's Disease: A Pilot Study Assessing Immune and Clinical Response|
|Study Start Date:||October 2001|
|Estimated Study Completion Date:||June 2008|
The purpose of this pilot study is to evaluate the immunologic and the clinical response to granulocyte-colony stimulating factor (G-CSF, Filgrastim, Neupogen) administered to patients with Crohn's Disease. Crohn's disease, an incurable, chronic, relapsing inflammation of the small and large intestine, affects approximately 500,000 people in the United States. The disease is characterized by full-thickness involvement of the gut wall leading to episodes of abdominal pain, diarrhea, hematochezia, weight loss and complications such as bowel obstruction, fistula formation and extraintestinal manifestations. The rationale for this study is based on several observations. First, it has been shown that effector T cells and dendritic cells harvested following G-CSF administration display a Th2 phenotype. Second, Crohn's disease in animal models has been characterized as a Th1 inflammatory disease that is susceptible to Th2 counter-regulation. Lastly, G-CSF has been an effective treatment in Crohn's disease as well as other colitides with resemblance to Crohn's disease according to published case reports. Despite the standard therapeutic use of steroids, aminosalicylates, antibiotics, antimetabolite immunosuppressants (6-MP, methotrexate), and early agents of the emerging biologics class of drugs (anti-TNFalpha antibodies, e.g.), the treatment of Crohn's disease is still troubled by loss of effectiveness of standard therapy over time, outright nonresponsiveness, and serious medication side effects. For these reasons newer agents and strategies for the treatment of Crohn's disease need to be developed and tested.
This pilot study proposes to measure the immunologic and clinical effect of two dose levels of G-CSF administered subcutaneously to patients with active Crohn's disease. The primary outcomes include documenting changes in immune parameters by measuring peripheral and lamina propria CD4 T cell cytokine release, dendritic cell phenotype and cytokine release, and changes in clinical parameters such as the Crohn's Disease Activity Index and endoscopic and histologic scores. Secondary endpoints include the rate and severity of adverse events. Our short-term goal is to document production of effector cells that have a Th2-cytokine profile and associate clinical improvement with these changes. The long-term goal of this study is to establish G-CSF as an effective alternative or adjunctive therapy with a low risk profile for the treatment of Crohn's disease.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|