Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Infliximab to Treat Crohn'S-like Inflammatory Bowel Disease in Chronic Granulomatous Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00325078
Recruitment Status : Terminated (Insufficient patient participation)
First Posted : May 12, 2006
Results First Posted : December 29, 2015
Last Update Posted : December 29, 2015
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Chronic Granulomatous Disease
Crohn'S-like IBD
Inflammatory Bowel Disease (IBD)
Intervention Drug: Infliximab
Enrollment 40
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Treatment Group Observation Group Control Volunteer
Hide Arm/Group Description

This group comprises patients with Chronic granulomatous disease (CGD) complicated by significant inflammatory bowel disease (IBD). The subjects are treated with a TNFa inhibitor at standard recommended doses for treatment of Crohn's disease. Infliximab is administered as intravenous infusions at 5mg/kg on weeks 0, 2 and 6 for induction and every 6-8 weeks at 5-10mg/kg for maintenance. Adalimumab is administered at 160mg, 60mg, 40mg, 40mg on weeks 0, 2, 4 and 6 via subcutaneous injection.

Endoscopies and gastrointestinal mucosal biopsies are obtained before treatment, following induction, and again at completion of treatment.

CGD patients with IBD who are not treated with any study medication and are monitored for rate of infections. Subjects who volunteer to participate in endoscopy and GI mucosal biopsies to provide controls for the study. The subjects in this arm may be healthy subjects, CGD subjects without GI symptoms, or subjects with Crohn's disease (CD). The rate of infections in the CGD patients without IBD are monitored.
Period Title: Overall Study
Started 8 7 25
Completed 3 2 23
Not Completed 5 5 2
Arm/Group Title Treatment Group Observation Group Control Volunteer Total
Hide Arm/Group Description

This group comprises patients with Chronic granulomatous disease (CGD) complicated by significant inflammatory bowel disease (IBD). The subjects are treated with a TNFa inhibitor at standard recommended doses for treatment of Crohn's disease. Infliximab is administered as intravenous infusions at 5mg/kg on weeks 0, 2 and 6 for induction and every 6-8 weeks at 5-10mg/kg for maintenance. Adalimumab is administered at 160mg, 60mg, 40mg, 40mg on weeks 0, 2, 4 and 6 via subcutaneous injection.

Endoscopies and gastrointestinal mucosal biopsies are obtained before treatment, following induction, and again at completion of treatment.

CGD patients with IBD who are not treated with any study medication and are monitored for rate of infections. Subjects who volunteer to participate in endoscopy and GI mucosal biopsies to provide controls for the study. The subjects in this arm may be healthy subjects, CGD subjects without GI symptoms, or subjects with Crohn's disease (CD). The rate of infections in the CGD patients without IBD are monitored. Total of all reporting groups
Overall Number of Baseline Participants 8 7 25 40
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 7 participants 25 participants 40 participants
<=18 years
1
  12.5%
3
  42.9%
0
   0.0%
4
  10.0%
Between 18 and 65 years
7
  87.5%
4
  57.1%
25
 100.0%
36
  90.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 7 participants 25 participants 40 participants
Female
1
  12.5%
0
   0.0%
6
  24.0%
7
  17.5%
Male
7
  87.5%
7
 100.0%
19
  76.0%
33
  82.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 7 participants 25 participants 40 participants
Hispanic or Latino
0
   0.0%
1
  14.3%
2
   8.0%
3
   7.5%
Not Hispanic or Latino
8
 100.0%
6
  85.7%
22
  88.0%
36
  90.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
1
   4.0%
1
   2.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 7 participants 25 participants 40 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
1
   4.0%
1
   2.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
6
  24.0%
6
  15.0%
White
8
 100.0%
6
  85.7%
15
  60.0%
29
  72.5%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
1
  14.3%
3
  12.0%
4
  10.0%
1.Primary Outcome
Title Safety of Study Drug
Hide Description Number of Infections from Baseline to 1 year
Time Frame Baseline to 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The volunteer group includes patients with chronic granulomatous disease as well as healthy normal volunteers as controls. Infection rates only pertain to and are counted in subjects with underlying immunodeficiency (chronic granulomatous disease).
Arm/Group Title Treatment Observation Control Volunteers
Hide Arm/Group Description:

This group comprises patients with Chronic granulomatous disease (CGD) complicated by significant inflammatory bowel disease (IBD). The subjects are treated with a TNFa inhibitor at standard recommended doses for treatment of Crohn's disease. Infliximab is administered as intravenous infusions at 5mg/kg on weeks 0, 2 and 6 for induction and every 6-8 weeks at 5-10mg/kg for maintenance. Adalimumab is administered at 160mg, 60mg, 40mg, 40mg on weeks 0, 2, 4 and 6 via subcutaneous injection.

Endoscopies and gastrointestinal mucosal biopsies are obtained before treatment, following induction, and again at completion of treatment.

Subjects with IBD without TNFa inhibitor treatment
Subjects who volunteer to participate in endoscopy and GI mucosal biopsies to provide controls for the study. The subjects in this arm may be healthy subjects, CGD subjects without GI symptoms, or subjects with Crohn's disease (CD). The rate of infections in the CGD patients without IBD are monitored.
Overall Number of Participants Analyzed 8 7 8
Measure Type: Number
Unit of Measure: infections
5 4 13
2.Primary Outcome
Title Efficacy of Treatment With Study Drug
Hide Description Measured participant Crohn's disease Activity Index (CDAI) values. The CDAI is a tool comprised of clinical and laboratory factors such as stool frequency, consistency, abdominal pain, general well being, weight and blood profile as an objective measure of disease activity. A higher score corresponds to greater severity of inflammatory bowel disease; severe disease conventionally defined as >450, a remission as <150, and a response to treatment as a fall of CDAI of >70 points. Infections and IBD are not expected in healthy control subjects. The greater the score, the more severe the disease, and a score of less than 5 represents clinical remission.
Time Frame Baseline, 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in the Treatment and Observation Arms with collected CDAI data. The CDAI, a tool validated for Crohn's disease is not applicable to healthy donors or CGD patients without IBD, and therefore not measured in the Control participants.
Arm/Group Title Treatment Observation
Hide Arm/Group Description:

This group comprises patients with Chronic granulomatous disease (CGD) complicated by significant inflammatory bowel disease (IBD). The subjects are treated with a TNFa inhibitor at standard recommended doses for treatment of Crohn's disease. Infliximab is administered as intravenous infusions at 5mg/kg on weeks 0, 2 and 6 for induction and every 6-8 weeks at 5-10mg/kg for maintenance. Adalimumab is administered at 160mg, 60mg, 40mg, 40mg on weeks 0, 2, 4 and 6 via subcutaneous injection.

Endoscopies and gastrointestinal mucosal biopsies are obtained before treatment, following induction, and again at completion of treatment.

CGD patients with IBD who are not treated with any study medication and are monitored for rate of infections.
Overall Number of Participants Analyzed 5 5
Measure Type: Number
Unit of Measure: Crohn's disease activity Index
CDAI Value #1 at Baseline 114.4 17.5
CDAI Value #2 at Baseline 191 22.5
CDAI Value #3 at Baseline 329.8 53
CDAI Value #4 at Baseline 505.2 159
CDAI Value #5 at Baseline 516 266.7
CDAI Value #1 at 1 year 95.5 NA [1] 
CDAI Value #2 at 1 year 138 NA [1] 
CDAI Value #3 at 1 year 185.4 NA [1] 
CDAI Value #4 at 1 year 259.2 NA [1] 
CDAI Value #5 at 1 year 295.2 NA [1] 
[1]
Only patients who completed the year of study drug treatment got a repeat CDAI
3.Other Pre-specified Outcome
Title Gut Immune Cell Types and Their Cytokine Profile
Hide Description Gut Immune cell types and their cytokine profile
Time Frame 1 year
Outcome Measure Data Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description The adverse events reported only relate to events occurring following study drug (TNFa inhibitors) treatment. Group 3 subjects who volunteered for endoscopy/gut biopsies are terminated at completion of the procedure. Baseline infections in endoscopy volunteers are not reported as adverse events.
 
Arm/Group Title Treatment Group Observation Group Control Volunteer
Hide Arm/Group Description

This group comprises patients with Chronic granulomatous disease (CGD) complicated by significant inflammatory bowel disease (IBD). The subjects are treated with a TNFa inhibitor at standard recommended doses for treatment of Crohn's disease. Infliximab is administered as intravenous infusions at 5mg/kg on weeks 0, 2 and 6 for induction and every 6-8 weeks at 5-10mg/kg for maintenance. Adalimumab is administered at 160mg, 60mg, 40mg, 40mg on weeks 0, 2, 4 and 6 via subcutaneous injection.

Endoscopies and gastrointestinal mucosal biopsies are obtained before treatment, following induction, and again at completion of treatment.

CGD patients with IBD who are not treated with any study medication and are monitored for rate of infections. Subjects who volunteer to participate in endoscopy and GI mucosal biopsies to provide controls for the study. The subjects in this arm may be healthy subjects, CGD subjects without GI symptoms, or subjects with Crohn's disease (CD). The rate of infections in the CGD patients without IBD are monitored.
All-Cause Mortality
Treatment Group Observation Group Control Volunteer
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
Treatment Group Observation Group Control Volunteer
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/8 (25.00%)   0/7 (0.00%)   0/25 (0.00%) 
Infections and infestations       
lung infection  1/8 (12.50%)  0/7 (0.00%)  0/25 (0.00%) 
Nervous system disorders       
Nervous system disorders - drug overdose  1/8 (12.50%)  0/7 (0.00%)  0/25 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Treatment Group Observation Group Control Volunteer
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/8 (37.50%)   1/7 (14.29%)   0/25 (0.00%) 
Gastrointestinal disorders       
diarrhea (clostridium diff)  1/8 (12.50%)  0/7 (0.00%)  0/25 (0.00%) 
General disorders       
Infusion related reaction  2/8 (25.00%)  0/7 (0.00%)  0/25 (0.00%) 
Surgical and medical procedures       
Infections and infestations, IV line infection  0/8 (0.00%)  1/7 (14.29%)  0/25 (0.00%) 
Due to limited subject participation and lack of sustained clinical benefits (1 year), there is insufficient complete data to generate meaningful statistics for the outcome measures. Instead, this data are reported as a case series.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: De Ravin, SukSee
Organization: National Institute of Allergy and Infectious Diseases
Phone: +1 301 496 6772
EMail: sderavin@mail.nih.gov
Layout table for additonal information
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
ClinicalTrials.gov Identifier: NCT00325078    
Other Study ID Numbers: 060160
06-I-0160
First Submitted: May 11, 2006
First Posted: May 12, 2006
Results First Submitted: March 18, 2014
Results First Posted: December 29, 2015
Last Update Posted: December 29, 2015