Crohn DiseaseNCT04272788
Association of Breg and Treg With the Clinical Effects of Infliximab in the Treatment of Patients With Crohn's Disease
An observational study of Crohn Disease, run by Second Affiliated Hospital of Wenzhou Medical University at 1 site in China.
Trial summary
Aims: The main aim of this study is to access the predictive value of Treg and Breg for the clinical effect of Infliximab in the treatment through analyzing the relationship between Breg and Treg and the efficacy of Infliximab. Design: It is a prospective, observational study. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Crohn Disease
- What is being tested?
- Infliximab
- Type of treatment
- Injection or infusion
- How many people
- 32 participants
- Where
- 1 siteChina
- Study dates
- 24 Jan 2017to 29 Sep 2019
- Phase
- Observational
- 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
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients from the gastroenterology department at the Second Affiliated Hospital of Wenzhou Medical University are eligible for entry. Healthy controls are recruited at Health Examination Center of the Second Affiliated Hospital of Wenzhou Medical University.
Who may be able to join
- Crohn's Disease at initial active stage with CDAI ≥150.
- Starting Infliximab treatment
- No current disease
- No daily drug use
Who cannot join
- Significant co-morbidity (e.g. cancer, intestinal tuberculosis, ischemic enteritis, radiation enteritis)
- Other immunological disease (e.g. diabetes, rheumatoid arthritis systemic lupus erythematosus)
- Current treatment with glucocorticoids, immunosuppressants and biological agents
- Healthy controls
- Significant co-morbidity (e.g. cancer, intestinal tuberculosis, ischemic enteritis, radiation enteritis)
- Other immunological disease (e.g. diabetes, rheumatoid arthritis systemic lupus erythematosus)
- Current treatment with glucocorticoids, immunosuppressants and biological agents
Trial locations and contacts
1 site in 1 country.
About this study
Aims: The main aim of this study is to access the predictive value of Treg and Breg for the clinical effect of Infliximab in the treatment through analyzing the relationship between Breg and Treg and the efficacy of Infliximab.
Design: It is a prospective, observational study. In the treatment group, 32 patients with Crohn's disease (CD) about to start Infliximab-treatment are recruited. They have blood samples drawn at week 0 and 14 of Infliximab treatment. 33 healthy individuals serve as a control group. Controls are only investigated once. All treatment and follow-up are according to national guidelines. The frequencies of Treg and Breg are investigated using flow cytometry. Subjects data are extracted from various registries.
Read the detailed description
- Patients with CD at initial active stage are collected from department of gastroenterology, the Second Affiliated Hospital of Wenzhou Medical University. The diagnosis of CD is based on clinical, endoscopic, laboratory, radiologic, histo-pathological findings and close follow-up in accordance with the guidelines for the diagnosis and treatment of CD issued by the European Crohn's Disease and Colitis in 2016. Healthy individuals are collected from the Health Examination Center of the Second Affiliated Hospital of Wenzhou Medical University as the healthy controls. The demographic and characteristic information of CD patients and healthy controls are recorded.
- Infliximab (5mg/kg) is given intravenously at week 0, 2 and 6 to induce CD remission, and then maintained with the same dose of Infliximab every 8 weeks.
- CD patients are followed for 14 weeks after the first administration of infliximab. At week 14 of Infliximab treatment, according to symptoms, CDAI and endoscopic mucosal healing, CD patients are classified as remission group (CDAI<150 and endoscopic mucosal healing, R group) and non-remission group (CDAI≥150 and/or mucosal non-healing group, N group).
- C-reactive protein (CRP), leucocyte count (WBC), platelet count (PLT), erythrocyte sedimentation rate (ESR) are detected in CD patients to assess the clinical efficacy at week 0 and 14 of Infliximab treatment respectively.
- Approximate 5 mL of peripheral fasting venous blood is obtained from every CD patient (at weeks 0 and 14 of Infliximab treatment) and healthy controls. Peripheral blood mononuclear cells (PBMCs) are isolated from the blood samples.
- Multi-color flow cytometry is applied to examine the frequency of Breg (CD3-CD19+IL-10+ B cell) in B cell: PBMCs are resuspended in RPMI 1640 medium, supplemented with 10% fetal bovine serum and 1% Penicillin/Streptomycin Solution, added in a 96-well flat-bottom culture plate. Then the obtained cells are stimulated with lipopolysaccharide for 48 hours, cultured at 37℃ in 5% CO2 in the incubator, and added Phorbol 12-myristate 13-acetate and ionomycin and Brefeldin A during the final 5 hours. After stimulated and cultured in vitro, PBMCs are stained with FITC-conjugated anti-human CD3 antibodies, APC-conjugated anti-human CD19 antibodies for 30 minutes with blocking light at 4℃. Then stained cells are fixed and permeabilized using a Cytofix/Cytoperm kit and stained with PE-conjugated anti-human IL-10 antibodies for 2 hours at 4℃ that protected form light. Flow staining buffer solution resuspends cells before flow cytometry detection of Breg.
- Multi-color flow cytometry is applied to examine the frequency of Treg (CD4+CD25+Foxp3+ T cell) in CD4+ T cell: PBMCs are stained with FITC-conjugated anti-human CD4 antibodies, APC-conjugated anti-human CD25 antibodies for 30 minutes with blocking light at 4℃. Stained cells are added fixing buffer and incubated at 4℃ in the dark overnight, then stained with PE-conjugated anti-human FoxP3 antibodies for 2 hours at 4℃ that protected form light. Flow staining buffer solution resuspends cells before flow cytometry detection of Treg.
- Conditions
- Crohn Disease
- Being tested
- Infliximab
- Keywords
- Crohn Disease, Infliximab, Treg, Breg
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InfliximabDrug
The CD patients at initial active stage without treatment of glucocorticoids, immunosuppressants and biological agents are included in the study when the decision to treat with Infliximab is already made. This study is observational, and all treatment and clinical follow-up are according to national guidelines.
| Study group | Role | What they receive |
|---|---|---|
| CD patients | CD patients about to start Infliximab treatment, gives as i.v. injection of 5 mg/kg at baseline, after 2 weeks, 6 weeks, and then every 8th week.CD patients are followed for 14 weeks after the first administration of infliximab. At week 14 of Infliximab treatment, CD patients are classified as remission group (CDAI<150 and endoscopic mucosal healing, R group) and non-remission group (CDAI≥150 and/or mucosal non-healing group, N group). Receives: Drug: Infliximab | |
| Healthy controls | Healthy controls without Crohn's Disease. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of the frequency of Treg in R group
The frequency of Treg is measured in peripheral blood by flow cytometry.
Measured: week 0 of Infliximab treatment, week 14 of Infliximab treatment
Change of the frequency of Breg in R group
The frequency of Breg is measured in peripheral blood by flow cytometry.
Measured: week 0 of Infliximab treatment, week 14 of Infliximab treatment
Change of the frequency of Treg in N group
The frequency of Treg is measured in peripheral blood by flow cytometry.
Measured: week 0 of Infliximab treatment, week 14 of Infliximab treatment
Change of the frequency of Breg in N group
The frequency of Breg is measured in peripheral blood by flow cytometry.
Measured: week 0 of Infliximab treatment, week 14 of Infliximab treatment
Secondary outcomes (10)
Change of Crohn's disease activity index (CDAI) in R group
CDAI is a measure of Crohn's Disease severity. CDAI < 150 is in remission stage, and ≥ 150 is in active stage. CDAI is negatively correlated with disease activity in CD patients.
Measured: week 0 of Infliximab treatment, week 14 of Infliximab treatment
Change of C-reactive protein (CRP) in R group
CRP is often combined to evaluate the disease activity of CD patients.The normal CRP range is (0-8) mg/L.Increased CRP indicates disease activity.
Measured: week 0 of Infliximab treatment, week 14 of Infliximab treatment
Change of leucocyte count (WBC) in R group
WBC is often combined to evaluate the disease activity of CD patients.The normal WBC range is (4-10)×109/L.Increased WBC indicates disease activity.
Measured: week 0 of Infliximab treatment, week 14 of Infliximab treatment
Change of platelet count (PLT) in R group
PLT is often combined to evaluate the disease activity of CD patients.The normal PLT range is (100-300)×109/L.Increased PLT indicates disease activity.
Measured: week 0 of Infliximab treatment, week 14 of Infliximab treatment
Change of erythrocyte sedimentation rate (ESR) in R group
ESR is often combined to evaluate the disease activity of CD patients.The normal ESR range is (0-15)mm/h.Increased ESR indicates disease activity.
Measured: week 0 of Infliximab treatment, week 14 of Infliximab treatment
Change of Crohn's disease activity index (CDAI) in N group
CDAI is a measure of Crohn's Disease severity. CDAI < 150 is in remission stage, and ≥ 150 is in active stage. CDAI is negatively correlated with disease activity in CD patients.
Measured: week 0 of Infliximab treatment, week 14 of Infliximab treatment
Change of C-reactive protein (CRP) in N group
CRP is often combined to evaluate the disease activity of CD patients.The normal CRP range is (0-8) mg/L.Increased CRP indicates disease activity.
Measured: week 0 of Infliximab treatment, week 14 of Infliximab treatment
Change of leucocyte count (WBC) in N group
WBC is often combined to evaluate the disease activity of CD patients.The normal WBC range is (4-10)×109/L.Increased WBC indicates disease activity.
Measured: week 0 of Infliximab treatment, week 14 of Infliximab treatment
Change of platelet count (PLT) in N group
PLT is often combined to evaluate the disease activity of CD patients.The normal PLT range is (100-300)×109/L.Increased PLT indicates disease activity.
Measured: week 0 of Infliximab treatment, week 14 of Infliximab treatment
Change of erythrocyte sedimentation rate (ESR) in N group
ESR is often combined to evaluate the disease activity of CD patients.The normal ESR range is (0-15)mm/h.Increased ESR indicates disease activity.
Measured: week 0 of Infliximab treatment, week 14 of Infliximab treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2020
- Study start24 Jan 2017
- Primary completion29 Sep 2019
- Study completion29 Sep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Crohn DiseaseStudies of the same condition, open and under way.
- More trials run by Second Affiliated Hospital of Wenzhou Medical UniversityThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yi Jiang, PhD, Principal investigator, Second Affiliated Hospital of Wenzhou Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04272788
- Sponsor's protocol ID
- SAHoWMU-CR2020-01-205
- Status last verified
- Feb 2020
- First submitted
- 11 Feb 2020
- Last updated
- 17 Feb 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Data sets will be made available on relevant requests and in accordance with journal guidelines when publishing results from this study.
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Association of Breg and Treg With the Clinical Effects of Infliximab in the Treatment of Patients With Crohn's Disease
- ClinicalTrials.gov ID
- NCT04272788
- Acronym / sponsor ID
- SAHoWMU-CR2020-01-205
- Conditions
- Crohn Disease
- Keywords
- Crohn Disease, Infliximab, Treg, Breg
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Second Affiliated Hospital of Wenzhou Medical UniversityUniversity, hospital or other
- Study start
- 24 Jan 2017 (actual)
- Primary completion
- 29 Sep 2019 (actual)
- Study completion
- 29 Sep 2019 (actual)
- First posted
- 17 Feb 2020 (actual)
- 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.
Aims: The main aim of this study is to access the predictive value of Treg and Breg for the clinical effect of Infliximab in the treatment through analyzing the relationship between Breg and Treg and the efficacy of Infliximab.
Design: It is a prospective, observational study. In the treatment group, 32 patients with Crohn's disease (CD) about to start Infliximab-treatment are recruited. They have blood samples drawn at week 0 and 14 of Infliximab treatment. 33 healthy individuals serve as a control group. Controls are only investigated once. All treatment and follow-up are according to national guidelines. The frequencies of Treg and Breg are investigated using flow cytometry. Subjects data are extracted from various registries.
Detailed description
- Patients with CD at initial active stage are collected from department of gastroenterology, the Second Affiliated Hospital of Wenzhou Medical University. The diagnosis of CD is based on clinical, endoscopic, laboratory, radiologic, histo-pathological findings and close follow-up in accordance with the guidelines for the diagnosis and treatment of CD issued by the European Crohn's Disease and Colitis in 2016. Healthy individuals are collected from the Health Examination Center of the Second Affiliated Hospital of Wenzhou Medical University as the healthy controls. The demographic and characteristic information of CD patients and healthy controls are recorded.
- Infliximab (5mg/kg) is given intravenously at week 0, 2 and 6 to induce CD remission, and then maintained with the same dose of Infliximab every 8 weeks.
- CD patients are followed for 14 weeks after the first administration of infliximab. At week 14 of Infliximab treatment, according to symptoms, CDAI and endoscopic mucosal healing, CD patients are classified as remission group (CDAI<150 and endoscopic mucosal healing, R group) and non-remission group (CDAI≥150 and/or mucosal non-healing group, N group).
- C-reactive protein (CRP), leucocyte count (WBC), platelet count (PLT), erythrocyte sedimentation rate (ESR) are detected in CD patients to assess the clinical efficacy at week 0 and 14 of Infliximab treatment respectively.
- Approximate 5 mL of peripheral fasting venous blood is obtained from every CD patient (at weeks 0 and 14 of Infliximab treatment) and healthy controls. Peripheral blood mononuclear cells (PBMCs) are isolated from the blood samples.
- Multi-color flow cytometry is applied to examine the frequency of Breg (CD3-CD19+IL-10+ B cell) in B cell: PBMCs are resuspended in RPMI 1640 medium, supplemented with 10% fetal bovine serum and 1% Penicillin/Streptomycin Solution, added in a 96-well flat-bottom culture plate. Then the obtained cells are stimulated with lipopolysaccharide for 48 hours, cultured at 37℃ in 5% CO2 in the incubator, and added Phorbol 12-myristate 13-acetate and ionomycin and Brefeldin A during the final 5 hours. After stimulated and cultured in vitro, PBMCs are stained with FITC-conjugated anti-human CD3 antibodies, APC-conjugated anti-human CD19 antibodies for 30 minutes with blocking light at 4℃. Then stained cells are fixed and permeabilized using a Cytofix/Cytoperm kit and stained with PE-conjugated anti-human IL-10 antibodies for 2 hours at 4℃ that protected form light. Flow staining buffer solution resuspends cells before flow cytometry detection of Breg.
- Multi-color flow cytometry is applied to examine the frequency of Treg (CD4+CD25+Foxp3+ T cell) in CD4+ T cell: PBMCs are stained with FITC-conjugated anti-human CD4 antibodies, APC-conjugated anti-human CD25 antibodies for 30 minutes with blocking light at 4℃. Stained cells are added fixing buffer and incubated at 4℃ in the dark overnight, then stained with PE-conjugated anti-human FoxP3 antibodies for 2 hours at 4℃ that protected form light. Flow staining buffer solution resuspends cells before flow cytometry detection of Treg.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CD patients | – | Drug: InfliximabCD patients about to start Infliximab treatment, gives as i.v. injection of 5 mg/kg at baseline, after 2 weeks, 6 weeks, and then every 8th week.CD patients are followed for 14 weeks after the first administration of infliximab. At week 14 of Infliximab treatment, CD patients are classified as remission group (CDAI<150 and endoscopic mucosal healing, R group) and non-remission group (CDAI≥150 and/or mucosal non-healing group, N group). |
| Healthy controls | – | –Healthy controls without Crohn's Disease. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients from the gastroenterology department at the Second Affiliated Hospital of Wenzhou Medical University are eligible for entry. Healthy controls are recruited at Health Examination Center of the Second Affiliated Hospital of Wenzhou Medical University.
Key inclusion criteria (4 listed)
- Crohn's Disease at initial active stage with CDAI ≥150.
- Starting Infliximab treatment
- No current disease
- No daily drug use
Key exclusion criteria (7 listed)
- Significant co-morbidity (e.g. cancer, intestinal tuberculosis, ischemic enteritis, radiation enteritis)
- Other immunological disease (e.g. diabetes, rheumatoid arthritis systemic lupus erythematosus)
- Current treatment with glucocorticoids, immunosuppressants and biological agents
- Healthy controls
- Significant co-morbidity (e.g. cancer, intestinal tuberculosis, ischemic enteritis, radiation enteritis)
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 |
|---|---|---|
| InfliximabThe CD patients at initial active stage without treatment of glucocorticoids, immunosuppressants and biological agents are included in the study when the decision to treat with Infliximab is already made. This study is observational, and all treatment and clinical follow-up are according to national guidelines. | Drug | CD patients |
Primary outcome
Change of the frequency of Treg in R group
Time frame: week 0 of Infliximab treatment, week 14 of Infliximab treatment
The frequency of Treg is measured in peripheral blood by flow cytometry.
Change of the frequency of Breg in R group
Time frame: week 0 of Infliximab treatment, week 14 of Infliximab treatment
The frequency of Breg is measured in peripheral blood by flow cytometry.
Change of the frequency of Treg in N group
Time frame: week 0 of Infliximab treatment, week 14 of Infliximab treatment
The frequency of Treg is measured in peripheral blood by flow cytometry.
Change of the frequency of Breg in N group
Time frame: week 0 of Infliximab treatment, week 14 of Infliximab treatment
The frequency of Breg is measured in peripheral blood by flow cytometry.
10 secondary outcomes
Change of Crohn's disease activity index (CDAI) in R group
Time frame: week 0 of Infliximab treatment, week 14 of Infliximab treatment
Change of C-reactive protein (CRP) in R group
Time frame: week 0 of Infliximab treatment, week 14 of Infliximab treatment
Change of leucocyte count (WBC) in R group
Time frame: week 0 of Infliximab treatment, week 14 of Infliximab treatment
Change of platelet count (PLT) in R group
Time frame: week 0 of Infliximab treatment, week 14 of Infliximab treatment
Change of erythrocyte sedimentation rate (ESR) in R group
Time frame: week 0 of Infliximab treatment, week 14 of Infliximab treatment
Change of Crohn's disease activity index (CDAI) in N group
Time frame: week 0 of Infliximab treatment, week 14 of Infliximab treatment
Change of C-reactive protein (CRP) in N group
Time frame: week 0 of Infliximab treatment, week 14 of Infliximab treatment
Change of leucocyte count (WBC) in N group
Time frame: week 0 of Infliximab treatment, week 14 of Infliximab treatment
Change of platelet count (PLT) in N group
Time frame: week 0 of Infliximab treatment, week 14 of Infliximab treatment
Change of erythrocyte sedimentation rate (ESR) in N group
Time frame: week 0 of Infliximab treatment, week 14 of Infliximab treatment
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 17 Feb 2020.
- Individual participant dataSharing planned: Undecided. Data sets will be made available on relevant requests and in accordance with journal guidelines when publishing results from this study.
Related trials for Crohn 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.
Yi Jiang, PhD principal investigator
Second Affiliated Hospital of Wenzhou Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Crohn Disease, run by Second Affiliated Hospital of Wenzhou Medical University at 1 site in China.
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 4 inclusion and 7 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 17 Feb 2020. 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 China. 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.
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.
What does the primary outcome measure?
Change of the frequency of Treg in R group (time frame: week 0 of Infliximab treatment, week 14 of Infliximab treatment). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Feb 2020.