Crohn's DiseasePhase 1NCT00025805
G-CSF to Treat Crohn's Disease
A Phase 1 study testing G-CSF in people with Crohn's Disease, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Crohn's Disease
- What is being tested?
- G-CSF
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Oct 2001to 13 Jun 2008
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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;
Show all 30Show fewer
- 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);
- high-dose inhaled corticosteroids or bronchodilators
- oral corticosteroids
- Current active bowel obstruction, intestinal perforation, significant GI hemorrhage, or known presence of high grade structure
- HIV positivity or signs and symptoms consistent with HIV infection
- Acute systemic or intestinal infection requiring antibiotics
- Active hepatitis B or C
- Decompensated liver disease (Childs-Pugh class B or C)
- Hematocrit less than 30 percent; Platelet count less than 100,000 or greater than 700,000; PT INR greater than 1.3 or PTT prolonged by greater than 3 seconds; serum creatinine or BUN greater than 1.5 times the upper limit of normal (ULN); ALT(SGPT) or AST(SGOT) greater than 2 times the ULN; total bilirubin greater than 1.25 times the ULN; alkaline phosphatase greater than 1.5 times the ULN.
- Pregnant or nursing women
- History of cancer (other than resected cutaneous basal or squamous cell carcinoma; and in situ cervical cancer) with less than 5 years documentation of a disease-free state
- History of myocardial infarction within the last 12 months
- Patients expected to require surgery for their Crohn's disease within 12 weeks of study entry.
- Any condition that, in the investigator's opinion, places the patient at undue risk by participating in the study.
- History of anaphylactic reaction or hypersensitivity to G-CSF (Filgrastim) or proteins derived from E. coli
- Presence of splenomegaly defined as a palpable spleen on physical exam.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Granulocyte-Colony Stimulating Factor Treatment for Crohn's Disease: A Pilot Study Assessing Immune and Clinical Response
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.
Read more
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
Read the detailed description
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.
- Conditions
- Crohn's Disease
- Being tested
- G-CSF
- Keywords
- Cytokines, Th1 Th2 Response, Inflammatory Bowel Dx, Lymphocyte, Colonoscopy, Crohn's Disease, Crohn's
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
G-CSFDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2001 (estimated)
- Study start23 Oct 2001
- Study completion13 Jun 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Crohn's DiseaseStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Enrolment
- 23 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00025805
- Sponsor's protocol ID
- 020019
- Other IDs
- 02-I-0019
- Status last verified
- 13 Jun 2008
- First submitted
- 25 Oct 2001
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
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.
PubMed 10631550
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Granulocyte-Colony Stimulating Factor Treatment for Crohn's Disease: A Pilot Study Assessing Immune and Clinical Response
- ClinicalTrials.gov ID
- NCT00025805
- Acronym / sponsor ID
- 020019
- Conditions
- Crohn's Disease
- Keywords
- Cytokines, Th1 Th2 Response, Inflammatory Bowel Dx, Lymphocyte, Colonoscopy, Crohn's Disease, Crohn's
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 23 Oct 2001
- Study completion
- 13 Jun 2008
- First posted
- 26 Oct 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
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.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (30 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| G-CSF | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 10631550Blumberg 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.
Related trials for Crohn's Disease
Not yet recruitingPhase 1
An Open-label, DDI Study to Investigate the Effects of Duvakitug on the PK of Selected Cytochrome P450 Substrates
Ulcerative Colitis, Crohn's Disease
RecruitingObservational study
Longitudinal Immunophenotyping of Patients With Inflammatory Bowel Disease
Inflammatory Bowel Disease, Crohn's Disease
RecruitingObservational study
Ibd CAncer and seRious Infections in France (I-CARE 2)
IBD, Ulcerative Colitis
RecruitingObservational study
Characterization of Colorectal Dysplasic Lesions and Stratification of Their Evolving Risk in Inflammatory Bowel Disease Patients: a Prospective, Observational and Multicenter Study
Crohn Disease (CD), Colitis Ulcerative
Enrolling by invitationPhase 4
MOdel-Informed Precision Dosing of Ustekinumab and VEdolizumab in Inflammatory Bowel Disease
Inflammatory Bowel Diseases, Crohn Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing G-CSF in people with Crohn's Disease, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00025805, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2017.