Ignite Creation Date:
2024-05-05 @ 11:46 AM
Last Modification Date:
2024-10-26 @ 9:13 AM
Study NCT ID:
NCT00128739
Status:
COMPLETED
Last Update Posted:
2005-08-29
First Post:
2005-08-09
Brief Title:
Treatment of Gastro-Intestinal andor Hepatic Graft Versus Host Disease With Budesonide in Patients Following Peripheral Blood Stem Cell Transplantation
Sponsor:
Rafa Laboratories
Organization:
Rafa Laboratories
Study Overview
Official Title:
A Phase 3 Study to Evaluate the Place of Budesonide in the Treatment of GVHD
Status:
COMPLETED
Status Verified Date:
2005-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Twenty-four 2 x 12 patients with intestinal graft versus host disease GVHD Grades 2 3 or 4 will be treated with budesonide 3mg three times daily or placebo for 12 weeks All of the patients will receive cyclosporine and by mouth po prednisone or intravenous IV methylprednisone with a starting dose of 2mgkgday standard anti-GVHD treatment Doses of steroids will be decreased by approximately 10 or 10mg per week depending upon patients weight upon response to therapy defined as a decrease of volume of diarrhea by 50 per day decrease in abdominal pain and no presence of bloody stool Patients with Grades 3 or 4 will be withdrawn from the study if there is no response after one week of therapy Patients with Grade 2 may continue with no decrease in prednisone dose until response is achieved
Detailed Description:
Graft versus host disease GVHD is one of the most common complications of bone marrow transplantation BMT Targets of GVHD are the gastro-intestinal tract GIT liver and skin causing severe diarrhea and mucosal aberration and hepatitis that can cause life threatening liver failure As a result of the mucosal aberration and the general immuno-suppression caused both by the GVHD process itself and by the anti GVHD therapy these patients are highly susceptible for severe life threatening infections that usually originate from the GIT Systemic steroids are the backbone of anti GVHD therapy However in GVHD systemic steroids have to be administered for a prolonged duration and in high doses thus causing prolonged immune suppression and exposing the patients to steroid side effects such as hypertension diabetes cataract formation etc
Budesonide is a steroid that combines topical anti-inflammatory activity with high first-pass hepatic extraction It was shown to be effective in treatment of inflammatory bowel disease with results slightly less then systemic steroids and fewer steroid-related adverse reactions Except for its influence on the gut budesonide was also shown to benefit inflammatory hepatic conditions such as primary biliary cirrhosis liver transplantation and autoimmune hepatitis Recently it has been shown that budesonide is an effective treatment in acute GIT GVHD The investigators propose to evaluate the effect of budesonide in GIT and hepatic GVHD with the following study
Patients
Twelve patients after allogenic peripheral blood stem cell transplantation PBSCT with grade 2 GIT andor hepatic GVHD will be prospectively compared to 12 placebo controls
Inclusion Criteria
Clinical and biopsy proven grade 2 GIT ANDOR hepatic GVHD
Exclusion Criteria
Preventive antimicrobial treatment with the exception of Resprim or somatostatin in the GIT GVHD patients
Anti-GVHD treatment other then steroids maximal dose 2 mgkg methylprednisolone and cyclosporine A or tacrolimus
Study Protocol
All patients will be assessed for GVHD scoring organ and general according to standard criteria and tested before inclusion for the following parameters -
Colon andor liver biopsy GVHD staging including number of crypt abscesses
Liver function tests - blood albumin AST ALT GGTP Alk Phos LDH bilirubin coagulation function cholesterol
Stool - volume and frequency
Radiological - CT scan for mucosal edema wall thickening and ascites
Kidney function tests - blood creatinine creatinine clearance
Blood pressure
Fasting blood glucose If normal - oral glucose tolerance test glycosylated hemoglobin
Ophthalmologist evaluation for cataract formation and IOP
GIT absorption assessment - xylose absorption
Microbiological - stool culture and stool for CDT CMV PCR culture for CMV in blood and urine
Bone density - by ultrasound
After inclusion the patients will be treated with budesonide 9 or 15mg per day in divided doses or placebo Other anti-GVHD treatment or ursodeoxycholic acid will not be withheld but tapering off will be tried
Study parameters
LFT albumin PT cholesterol renal function stool volume and frequency CMV culture and PCR clinical GVHD staging - every 2 weeks
Xylose test - every month
Ophthalmologist evaluation diabetes control and CT scan - every 3 months
GIT andor liver biopsy for GVHD staging including number of crypt abscesses and CMV PCR bone density - every 6 months
Blood urine and stool culture during every febrile episode
Study duration 14 weeks
End points
Hospitalizations due to GVHD andor due to infections
Overall and GIT or hepatic GVHD staging
Time to response
Maximal daily diarrhea volume and frequency
Weight
Liver function tests
Cataract formation and IOP
TNF level
Albumin
TPN consumption
Bone density
Hypertension
Diabetes - presence and control
Febrile episodes
Positive cultures
Days of antibiotic therapy
Survival
Budesonide is a steroid that combines topical anti-inflammatory activity with high first-pass hepatic extraction It was shown to be effective in treatment of inflammatory bowel disease with results slightly less then systemic steroids and fewer steroid-related adverse reactions Except for its influence on the gut budesonide was also shown to benefit inflammatory hepatic conditions such as primary biliary cirrhosis liver transplantation and autoimmune hepatitis Recently it has been shown that budesonide is an effective treatment in acute GIT GVHD The investigators propose to evaluate the effect of budesonide in GIT and hepatic GVHD with the following study
Patients
Twelve patients after allogenic peripheral blood stem cell transplantation PBSCT with grade 2 GIT andor hepatic GVHD will be prospectively compared to 12 placebo controls
Inclusion Criteria
Clinical and biopsy proven grade 2 GIT ANDOR hepatic GVHD
Exclusion Criteria
Preventive antimicrobial treatment with the exception of Resprim or somatostatin in the GIT GVHD patients
Anti-GVHD treatment other then steroids maximal dose 2 mgkg methylprednisolone and cyclosporine A or tacrolimus
Study Protocol
All patients will be assessed for GVHD scoring organ and general according to standard criteria and tested before inclusion for the following parameters -
Colon andor liver biopsy GVHD staging including number of crypt abscesses
Liver function tests - blood albumin AST ALT GGTP Alk Phos LDH bilirubin coagulation function cholesterol
Stool - volume and frequency
Radiological - CT scan for mucosal edema wall thickening and ascites
Kidney function tests - blood creatinine creatinine clearance
Blood pressure
Fasting blood glucose If normal - oral glucose tolerance test glycosylated hemoglobin
Ophthalmologist evaluation for cataract formation and IOP
GIT absorption assessment - xylose absorption
Microbiological - stool culture and stool for CDT CMV PCR culture for CMV in blood and urine
Bone density - by ultrasound
After inclusion the patients will be treated with budesonide 9 or 15mg per day in divided doses or placebo Other anti-GVHD treatment or ursodeoxycholic acid will not be withheld but tapering off will be tried
Study parameters
LFT albumin PT cholesterol renal function stool volume and frequency CMV culture and PCR clinical GVHD staging - every 2 weeks
Xylose test - every month
Ophthalmologist evaluation diabetes control and CT scan - every 3 months
GIT andor liver biopsy for GVHD staging including number of crypt abscesses and CMV PCR bone density - every 6 months
Blood urine and stool culture during every febrile episode
Study duration 14 weeks
End points
Hospitalizations due to GVHD andor due to infections
Overall and GIT or hepatic GVHD staging
Time to response
Maximal daily diarrhea volume and frequency
Weight
Liver function tests
Cataract formation and IOP
TNF level
Albumin
TPN consumption
Bone density
Hypertension
Diabetes - presence and control
Febrile episodes
Positive cultures
Days of antibiotic therapy
Survival
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None