Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Identification of Scores Associated With a Favorable Clinical Response With Thiopurines in IBD Patients (SCORE1)

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: NCT02367326
Recruitment Status : Completed
First Posted : February 20, 2015
Last Update Posted : August 22, 2017
Sponsor:
Collaborator:
Apsen Farmaceutica S.A.
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Saint Etienne

Brief 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. 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).

Condition or disease Intervention/treatment
Inflammatory Bowel Diseases Other: data collection

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.

Layout table for study information
Study Type : Observational
Actual Enrollment : 400 participants
Observational Model: Cohort
Time Perspective: Prospective
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
Actual Study Start Date : June 2014
Actual Primary Completion Date : June 2017
Actual Study Completion Date : August 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease

Group/Cohort Intervention/treatment
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
Other: data collection
data collection will be carried out by the investigator during a standard hospitalization of the patient




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. number of patient in clinical remission on thiopurines [ Time Frame: day 0 (inclusion) ]

    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
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
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02367326


Locations
Layout table for location information
France
CHU Jean Minjoz
Besançon, France, 25030
CHU Caen
Caen, France, 14033
CHU Dijon
Dijon, France, 21079
CHRU Lilles
Lilles, France, 59037
CHU Montpellier
Montpellier, France, 34295
CHU Nancy
Nancy, France, 54511
CHU Nantes - Hôtel-Dieu
Nantes, France, 44093
CHU Nice
Nice, France, 06200
CHR Orléans
Orléans, France, 45000
Hôpital Saint-Antoine
Paris, France, 75012
CHU Bordeaux
Pessac, France, 33604
CH Lyon Sud
Pierre Bénite, France, 69310
CHU Reims
Reims, France, 51092
CHU Rennes
Rennes, France, 35033
CHU Saint-Etienne
Saint-Etienne, France, 42055
Sponsors and Collaborators
Centre Hospitalier Universitaire de Saint Etienne
Apsen Farmaceutica S.A.
Investigators
Layout table for investigator information
Principal Investigator: Xavier ROBLIN, MD CHU Saint-Etienne

Layout table for additonal information
Responsible Party: Centre Hospitalier Universitaire de Saint Etienne
ClinicalTrials.gov Identifier: NCT02367326     History of Changes
Other Study ID Numbers: 1208169
DR-2012-589 ( Other Identifier: CNIL )
First Posted: February 20, 2015    Key Record Dates
Last Update Posted: August 22, 2017
Last Verified: August 2017

Keywords provided by Centre Hospitalier Universitaire de Saint Etienne:
score
inflammatory bowel disease
crohn's disease
ulcerative colitis
clinical response
thiopurines

Additional relevant MeSH terms:
Layout table for MeSH terms
Intestinal Diseases
Inflammatory Bowel Diseases
Gastrointestinal Diseases
Digestive System Diseases
Gastroenteritis