G-CSF to Treat Crohn's Disease

NCT00025805 | Completed Phase 1

• 2 other identifiers: 02001902-I-0019
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Crohn's Disease

Keywords

Cytokines; Th1 Th2 Response; Inflammatory Bowel Dx; Lymphocyte; Colonoscopy; Crohn's Disease; Crohn's

Interventions

G-CSF DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects must have a verifiable diagnosis of active Crohn's disease of at least 4 months' duration. The diagnosis must be supported by characteristic 1) endoscopic or radiographic findings and 2) histopathologic changes on endoscopic biopsy or resected tissue.
• All subjects must be over age 18.
• The Crohn's disease is mildly to moderately active based on a Crohn's Disease Activity Index score between 225 and 450 (with either a diarrhea rating or abdominal pain rating of greater than or equal to 25).
• If currently receiving any medications for Crohn's disease, subjects may only be on a stable regimen of one or a combination of the following drug doses and durations: antibiotic therapy for greater than or equal to 2 weeks; Corticosteroids (less than or equal to 25 mg Prednisone/d, or Prednisone equivalent) for greater than or equal to 4 weeks; 5-ASA/Sulfasalazine for greater than or equal to 4 weeks; azathioprine/6-MP for greater than or equal to 8 weeks (Note: patients receiving Azathioprine or 6-MP must have been receiving these medications for greater than or equal to 12 weeks before randomization.); Probiotics for greater than or equal to 4 weeks.
• Use of barrier or hormonal methods of birth control for male and famale subjects who are not surgically sterile or postmenopausal.
• Negative serum beta-hCG for women of child-bearing potential (women who are not surgically sterile or postmenopausal) to exclude early pregnancy.
• Negative results on stool examination for culture of enteric pathogens (Salmonella, Shigella, Yersinia, Campylobacter, Vibrio, E. coli O157/H7), Clostridia difficile toxin assay, enteric parasites and their ova (including Giardia and Cryptosporidia).

You may not qualify if:

• If any one of the above eligibility requirements is not met.
• Use of any the following medications within the specified time period prior to the first dose of study drug or at any time during the study: Corticosteroid enema or 5-ASA enema or suppositories (7 days); Thalidomide (2 weeks); Corticosteroids (greater than 25 mg Prednisone/d or Prednisone equivalent) (4 weeks); Methotrexate, Cyclosporin, Tacrolimus (FK506, Prograf), Thalidomide, or Mycophenolate mofetil (CellCept) (4 weeks), or any biological therapy (cytokine, anti-cytokine, or integrin-based therapy); Monoclonal antibodies to TNF (4 months); any experimental agent (1 month); use of greater than 500 mg/d aspirin or any dose of other NSAID (24 hours).
• Multiple bowel resections (greater than or equal to 200 cm) AND enteral or parenteral therapy to maintain weight.
• Use of any other investigational agent within 30 days beginning the treatment phase of this study.
• Any of the following abnormalities on an electrocardiogram: QT(c) greater than 0.48 sec, Mobitz type II second or third degree atrioventricular block, left bundle branch block or right bundle branch block with any fascicular block, changes consistent with acute ischemia.
• A diagnosis of ulcerative colitis or indeterminate colitis;
• Cushing's syndrome;
• Coexisting Th2-type inflammatory diseases: a.) scleroderma b.) MODERATE persistent asthma defined as the presence of one of the features listed below:
• Clinical features before treatment: daily symptoms, exacerbations that affect activity and sleep, nighttime asthma symptoms two to four times a week, peak expiratory flow (PEF) or forced expiratory volume (FEV1) greater than 60 percent to less than 80 percent of predicted, variability greater than 30 percent;
• Daily medication required to maintain control:
• Daily controller medication (especially for nighttime symptoms): inhaled corticosteroids and long acting bronchodilators
• SEVERE persistent asthma defined as the presence of one of the features listed below:
• Clinical features before treatment: continuous symptoms, frequent exacerbations, frequent nighttime asthma symptoms more than 4 times a week, daily physical activities limited by asthma symptoms, PEF or FEV1 less than 60 percent predicted, variability greater than 30 percent;
• Daily medication required to maintain control:
• Multiple daily controller medications (long-term);

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Blumberg RS, Saubermann LJ, Strober W. Animal models of mucosal inflammation and their relation to human inflammatory bowel disease. Curr Opin Immunol. 1999 Dec;11(6):648-56. doi: 10.1016/s0952-7915(99)00032-1.

  PMID: 10631550 BACKGROUND

MeSH Terms

Conditions

Crohn Disease

Interventions

Granulocyte Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: October 25, 2001
• First Posted: October 26, 2001
• Study Start: October 23, 2001
• Study Completion: June 13, 2008
• Last Updated: July 2, 2017

Record last verified: 2008-06-13

Locations

US (1)