Inflammatory Bowel DiseasesSCORE1NCT02367326
Identification of Scores Associated With a Favorable Clinical Response With Thiopurines in IBD Patients
An observational study of Inflammatory Bowel Diseases, run by Centre Hospitalier Universitaire de Saint Etienne at 15 sites in France.
Trial summary
Inflammatory bowel disease (IBD) groups together Crohn's Disease (CD) and ulcerative colitis (UC). Its prevalence is high representing approximately 0.4% of the population. The peak incidence for these diseases ranges between 2 and 30 years of age with a second peak for CD recently reported at 60. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Inflammatory Bowel Diseases
- What is being tested?
- data collection
- How many people
- 400 participants
- Where
- 15 sitesFrance
- Study dates
- Jun 2014to Aug 2017
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: patients with Crohn's Disease or Ulcerative Colitis and on thiopurines at stable doses for at least 3 months, monotherapy or combined with corticotherapy
Who may be able to join
- Adult patients affiliated with or beneficiaries of a national health insurance scheme
- Male our female over 18 years of age and under 70 having given his/her informed consent to participate in this trial.
- Any patients with Crohn's Disease or Ulcerative Colitis meeting clinical, endoscopic and histological criteria.
- Patients on thiopurines at stable doses for at least 3 months, monotherapy or combined with corticotherapy using the following doses:
- AZATHIOPRINE at the dose of 2 to 2.5 mg/kg/day, regular oral dosing for 3 months or PURINETHOL at the dose of 1 to 1.5 mg/kg/day, regular oral dosing for 3 months
Who cannot join
- Patients with intolerance to thiopurines resulting in reduction or discontinuation of thiopurines by the referring physician.
- Post operative Crohn's Disease patients for whom thiopurines were indicated preventively or in the event of endoscopic abnormalities.
- Extensive colic resection, (sub)total colectomy.
- History of > 3 resections of the small intestine or diagnosis of a short bowel
- Crohn's Disease with a perianal lesion whether the latter is isolated or the focus of the disease
- Patient with a enterocutaneous, abdominal or pelvic fistula with abscess or fistula likely to require surgery during the study
Show all 13Show fewer
- Ileostomy, colostomy or known intestinal stenosis
- Severe active infection
- Active neoplasia
- Known TPMPT homozygote mutation
- Patients on anti-TNF or Methotrexate in the last 3 months or during thiopurine therapy
- Patients on Allopurinol.
- Patient who expressed his/her refusal to participate in the study
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
France15 sites
CHU Jean Minjoz
Besançon, 25030
CHU Caen
Caen, 14033
CHU Dijon
Dijon, 21079
CHRU Lilles
Lilles, 59037
CHU Montpellier
Montpellier, 34295
CHU Nancy
Nancy, 54511
CHU Nantes - Hôtel-Dieu
Nantes, 44093
CHU Nice
Nice, 06200
CHR Orléans
Orléans, 45000
Hôpital Saint-Antoine
Paris, 75012
CHU Bordeaux
Pessac, 33604
CH Lyon Sud
Pierre-Bénite, 69310
CHU Reims
Reims, 51092
CHU Rennes
Rennes, 35033
CHU Saint-Etienne
Saint-Etienne, 42055
About this study
Official title: Identification of Composite Clinical and Lab Scores Associated With a Favorable Clinical Response With Thiopurines in Patients With IBD (Inflammatory Bowel Disease): an International Clinical Trial
Inflammatory bowel disease (IBD) groups together Crohn's Disease (CD) and ulcerative colitis (UC). Its prevalence is high representing approximately 0.4% of the population. The peak incidence for these diseases ranges between 2 and 30 years of age with a second peak for CD recently reported at 60. These diseases develop over time into complications requiring in 2/3 of cases surgical resection procedures in CD and colectomy in over 20% of cases. Cohort data has recently shown that the early use of azathioprine from the first year would decrease the need for surgery. Aside from biologics, azathioprine is the most widely used immunosuppressant in IBD management. Its metabolism is highly variable in the overall population since over 10% of patients are slow metabolizers and 15% fast metabolizers. This explains partly treatment failures and side effects with thiopurines. A lot of research has shown that metabolite measurement of azathioprine (6-TGN end methylated derivatives) could be used clinically even if these results remain controversial. In fact, their positive predicative value (PPV) in clinical response does not exceed 60%. This costly testing cannot be done everywhere, is not reimbursed by national health services, and may not be used in some countries. It is, however, key in order optimize these drugs at a time when only two anti-TNFs are possible in the event of failure on thiopurines. Older studies have shown that MCV and lymphonenia could be markers for thiopurine impregnation. Recently, an American study provided a mathematic formula enabling to achieve over 80% PPV for the clinical response on AZA but this calculation needs to be confirmed and it is, moreover, patented (costly).
Read the detailed description
We suggest developing a predictive score for clinical thiopurines in IBD based on routine lab data obtained when monitoring patients on thiopurines. This initial work will enable to identify clinical and/or lab factors in order to develop a score based on an international, multicenter, cross-section study. Two hundred patients with treatment failure on thiopurines will be included and at least as many in clinical remission on thiopurines. A subsequent longitudinal study, over all recruiting centers will enable to validate the score. Finally, a prospective study will assess the clinical impact of the optimization of this score in patients sustaining a treatment failure on thiopurines. This score - if confirmed - will subsequently be at no additional cost in the management of patients on thiopurines.
- Conditions
- Inflammatory Bowel Diseases
- Being tested
- data collection
- Keywords
- score, inflammatory bowel disease, crohn's disease, ulcerative colitis, clinical response, thiopurines
- Medical subject headings
- Inflammatory Bowel Diseases, Crohn Disease, Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
data collectionOther
data collection will be carried out by the investigator during a standard hospitalization of the patient
| Study group | Role | What they receive |
|---|---|---|
| Patients with Inflammatory Bowel Disease | patients with Crohn's Disease or Ulcerative Colitis meeting clinical, endoscopic and histological criteria and on thiopurines at stable doses for at least 3 months, monotherapy or combined with corticotherapy Receives: Other: data collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
number of patient with therapeutic failure on thiopurines
A therapeutic failure on thiopurines will be considered to be any patient with at least one of the following criteria:
- For Crohn's Disease: a HBI score > 4
- For Ulcerative Colitis: a partial Mayo score > 2 or activity reported by the expert at the time of a visit
- For both disease:
- Corticodependence, defined according to ECCO criteria, as an impossibility to reduce the dose of Prednisolone to less than 10 mg/day (or 3 mg/day for Budesonide) in the 3 months following corticotherapy induction.
- Corticoresistance, defined according to ECCO criteria, as a lack of response to the dose of 0.75mg/kg of a Prednisone equivalent for 4 weeks.
- the need to change treatment or a surgical indication.
Measured: day 0 (inclusion)
Secondary outcomes (1)
number of patient in clinical remission on thiopurines
A clinical remission shall be considered as any patients with at least one of the following criteria:
- For Crohn's Disease: a HBI score < 4
- For ulcerative colitis: a partial Mayo score ≤ 2 with no subscore > 1
- For both diseases, no corticotherapy for at least 3 months.
Measured: day 0 (inclusion)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2015 (estimated)
- Study startJun 2014
- Primary completionJun 2017
- Study completionAug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Inflammatory Bowel DiseasesStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de Saint EtienneThe 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
- 400 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Apsen Farmaceutica S.A.
- Responsible party
- Sponsor
- Investigators
- Xavier ROBLIN, MD, Principal investigator, Centre Hospitalier Universitaire de Saint Etienne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02367326
- Sponsor's protocol ID
- 1208169
- Other IDs
- DR-2012-589
- Acronym
- SCORE1
- Status last verified
- Aug 2017
- First submitted
- 12 Feb 2015
- Last updated
- 22 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identification of Composite Clinical and Lab Scores Associated With a Favorable Clinical Response With Thiopurines in Patients With IBD (Inflammatory Bowel Disease): an International Clinical Trial
- ClinicalTrials.gov ID
- NCT02367326
- Acronym / sponsor ID
- SCORE1 / 1208169
- Conditions
- Inflammatory Bowel Diseases
- Keywords
- score, inflammatory bowel disease, crohn's disease, ulcerative colitis, clinical response, thiopurines
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 400 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire de Saint EtienneUniversity, hospital or other
- Collaborators
- Apsen Farmaceutica S.A.
- Study start
- Jun 2014 (actual)
- Primary completion
- Jun 2017 (actual)
- Study completion
- Aug 2017 (actual)
- First posted
- 20 Feb 2015 (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.
Inflammatory bowel disease (IBD) groups together Crohn's Disease (CD) and ulcerative colitis (UC). Its prevalence is high representing approximately 0.4% of the population. The peak incidence for these diseases ranges between 2 and 30 years of age with a second peak for CD recently reported at 60. These diseases develop over time into complications requiring in 2/3 of cases surgical resection procedures in CD and colectomy in over 20% of cases. Cohort data has recently shown that the early use of azathioprine from the first year would decrease the need for surgery. Aside from biologics, azathioprine is the most widely used immunosuppressant in IBD management. Its metabolism is highly variable in the overall population since over 10% of patients are slow metabolizers and 15% fast metabolizers. This explains partly treatment failures and side effects with thiopurines. A lot of research has shown that metabolite measurement of azathioprine (6-TGN end methylated derivatives) could be used clinically even if these results remain controversial. In fact, their positive predicative value (PPV) in clinical response does not exceed 60%. This costly testing cannot be done everywhere, is not reimbursed by national health services, and may not be used in some countries. It is, however, key in order optimize these drugs at a time when only two anti-TNFs are possible in the event of failure on thiopurines. Older studies have shown that MCV and lymphonenia could be markers for thiopurine impregnation. Recently, an American study provided a mathematic formula enabling to achieve over 80% PPV for the clinical response on AZA but this calculation needs to be confirmed and it is, moreover, patented (costly).
Detailed description
We suggest developing a predictive score for clinical thiopurines in IBD based on routine lab data obtained when monitoring patients on thiopurines. This initial work will enable to identify clinical and/or lab factors in order to develop a score based on an international, multicenter, cross-section study. Two hundred patients with treatment failure on thiopurines will be included and at least as many in clinical remission on thiopurines. A subsequent longitudinal study, over all recruiting centers will enable to validate the score. Finally, a prospective study will assess the clinical impact of the optimization of this score in patients sustaining a treatment failure on thiopurines. This score - if confirmed - will subsequently be at no additional cost in the management of patients on thiopurines.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with Inflammatory Bowel Disease | – | Other: data collectionpatients with Crohn's Disease or Ulcerative Colitis meeting clinical, endoscopic and histological criteria and on thiopurines at stable doses for at least 3 months, monotherapy or combined with corticotherapy |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- patients with Crohn's Disease or Ulcerative Colitis and on thiopurines at stable doses for at least 3 months, monotherapy or combined with corticotherapy
Key inclusion criteria (5 listed)
- Adult patients affiliated with or beneficiaries of a national health insurance scheme
- Male our female over 18 years of age and under 70 having given his/her informed consent to participate in this trial.
- Any patients with Crohn's Disease or Ulcerative Colitis meeting clinical, endoscopic and histological criteria.
- Patients on thiopurines at stable doses for at least 3 months, monotherapy or combined with corticotherapy using the following doses:
- AZATHIOPRINE at the dose of 2 to 2.5 mg/kg/day, regular oral dosing for 3 months or PURINETHOL at the dose of 1 to 1.5 mg/kg/day, regular oral dosing for 3 months
Key exclusion criteria (13 listed)
- Patients with intolerance to thiopurines resulting in reduction or discontinuation of thiopurines by the referring physician.
- Post operative Crohn's Disease patients for whom thiopurines were indicated preventively or in the event of endoscopic abnormalities.
- Extensive colic resection, (sub)total colectomy.
- History of > 3 resections of the small intestine or diagnosis of a short bowel
- Crohn's Disease with a perianal lesion whether the latter is isolated or the focus of the disease
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 |
|---|---|---|
| data collectiondata collection will be carried out by the investigator during a standard hospitalization of the patient | Other | Patients with Inflammatory Bowel Disease |
Primary outcome
number of patient with therapeutic failure on thiopurines
Time frame: day 0 (inclusion)
A therapeutic failure on thiopurines will be considered to be any patient with at least one of the following criteria: * For Crohn's Disease: a HBI score > 4 * For Ulcerative Colitis: a partial Mayo score > 2 or activity reported by the expert at the time of a visit * For both disease: * Corticodependence, defined according to ECCO criteria, as an impossibility to reduce the dose of Prednisolone to less than 10 mg/day (or 3 mg/day for Budesonide) in the 3 months following corticotherapy induction. * Corticoresistance, defined according to ECCO criteria, as a lack of response to the dose of 0.75mg/kg of a Prednisone equivalent for 4 weeks. * the need to change treatment or a surgical indication.
1 secondary outcome
number of patient in clinical remission on thiopurines
Time frame: day 0 (inclusion)
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 22 Aug 2017.
Related trials for Inflammatory Bowel Diseases
Recruiting
Effect of Mediterranean Diet in Inflammatory Bowel Disease
Inflammatory Bowel Disease
Enrolling by invitationPhase 4
MOdel-Informed Precision Dosing of Ustekinumab and VEdolizumab in Inflammatory Bowel Disease
Inflammatory Bowel Diseases, Crohn Disease
RecruitingObservational study
Longitudinal Immunophenotyping of Patients With Inflammatory Bowel Disease
Inflammatory Bowel Disease, Crohn's Disease
RecruitingObservational study
Clinical and Basic Investigations Into Hermansky-Pudlak Syndrome
Hermansky-Pudlak Syndrome (HPS)
RecruitingPhase 1
A Sub Study to Investigate the Safety and Tolerability of Aletekitug in Participants With Moderate To Severe Ulcerative Colitis
Colitis, Ulcerative
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.
Xavier ROBLIN, MD principal investigator
Centre Hospitalier Universitaire de Saint Etienne
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Inflammatory Bowel Diseases, run by Centre Hospitalier Universitaire de Saint Etienne at 15 sites in France.
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 5 inclusion and 13 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 22 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in France. 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?
number of patient with therapeutic failure on thiopurines (time frame: day 0 (inclusion)). 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 22 Aug 2017; AzTrials last refreshed its copy on 8 Nov 2026.