ulcerative colitis MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856 MedDRA version: 20.0 Level: PT Classification code 10009790 Term: Coagulation time System Organ Class: 10022891 - Investigations MedDRA version: 21.0 Level: PT Classification code 10061684 Term: Platelet function test System Organ Class: 10022891 - Investigations
Conditions
Interventions
Trade Name: Adalimumab
Pharmaceutical Form: Injection
INN or Proposed INN: ADALIMUMAB
CAS Number: 331731-18-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-
T
Sponsors
Fundación Española de Gastroenterología
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: EX VIVO STUDY IN PATIENTS WITH UC PATIENTS WITH UC: - Over 18 years old. - Diagnosis of UC according to the criteria of the European Crohn’s and Colitis Organisation (ECCO). - Previous treatments are allowed, provided they have remained stable for the past 3 months. - In the case of patients with active UC, they should have endoscopic activity within 1 month of starting the treatment (Mayo endoscopic sub-index of = 2). -Women of childbearing potential who use methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods. Such methods include: intrauterine device (IUD) bilateral tubal occlusion vasectomised partner sexual abstinence Or women of childbearing potential who use a combination of male condom with either cap, diaphragm or sponge with spermicide INDIVIDUALS WITHOUT UC: - Over 18 years old. - Subjects not diagnosed with UC, or other inflammatory allergic, malignant or autoimmune diseases. - Women of childbearing potential who use methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods. Such methods include: intrauterine device (IUD) bilateral tubal occlusion vasectomised partner sexual abstinence Or women of childbearing potential who use a combination of male condom with either cap, diaphragm or sponge with spermicide IN VIVO STUDY IN PATIENTS WITH UC PATIENTS WITH UC: - Over 18 years old. - Diagnosis of UC according to the criteria of the European Crohn’s and Colitis Organisation (ECCO). - Have indication of treatment with anti-TNFa (infliximab, adalimumab or golimumab) o tofacitinib. - Be the first received JAK-inhibitor or anti-TNFa with a given mechanism of action and have endoscopic activity of UC within 1 month of starting the treatment (Mayo endoscopic sub-index of = 2). - Previous treatments (including corticosteroids and immunosuppressants) are allowed provided that they have been stable for the last 3 months before beginning treatment with JAK-inhibitor or anti-TNFa and that they are maintained at a stable dose for the duration of the study -Women of childbearing potential who use methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods. Such methods include: intrauterine device (IUD) bilateral tubal occlusion vasectomised partner sexual abstinence Or women of childbearing potential who use a combination of male condom with either cap, diaphragm or sponge with spermicide INDIVIDUALS WITHOUT UC: - Over 18 years old. - Subjects not diagnosed with UC, or other inflammatory, allergic, malignant or autoimmune diseases. - Women of childbearing potential who use methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods. Such methods include: intrauterine device (IUD) bilateral tubal occlusion vasectomised partner sexual abstinence Or women of childbearing potential who use a combination of male condom with either cap, diaphragm or sponge with spermicide Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: EX VIVO STUDY IN PATIENTS WITH UC PATIENTS WITH UC: - Under 18 years old. - Immune-mediated disease, neoplasm or active infection. - Pregnancy or lactation. - Alcohol or drug abuse. - Ostomy. - Abdominal surgery in the last 6 months. - Colectomy. - Active infection with hepatitis B, C or HIV virus. - Medical history of thromboembolic events. -Treatment with anticoagulants, antiplatelets or other drugs that alter the coagulation. - Use of combined hormonal contraceptives or hormone replacement therapy. - Hereditary coagulation disorders. - Refusal to give consent for participation in the study. INDIVIDUALS WITHOUT UC: - Under 18 years of age. - Advanced chronic disease or any other pathology that prevents the monitoring of the protocol of this study. - Pregnancy or lactation. - Alcohol or drug abuse. - Ostomy. - Abdominal surgery in the last 6 months. - Colectomy. - Active infection with hepatitis B, C or HIV virus. - Medical history of thromboembolic events. -Treatment with anticoagulants, antiplatelets or other drugs that alter the coagulation. - Use of combined hormonal contraceptives or hormone replacement therapy. - Hereditary coagulation disorders. - Refusal to give consent for participation in the study. IN VIVO STUDY IN PATIENTS WITH UC PATIENTS WITH UC: - Under 18 years old. - Immune-mediated disease. - Neoplasm or active infection. - Pregnancy or lactation. - Alcohol or drug abuse. - Ostomy. - Abdominal surgery in the last 6 months. - Colectomy. - Active infection with hepatitis B, C or HIV virus. - Indication of anti-TNFa or JAK-inhibitors treatment for a cause other than UC. - Have previously received a drug with the same mechanism of action (anti-TNFa or JAK-inhibitors) - Medical history of thromboembolic events. -Treatment with anticoagulants, antiplatelets or other drugs that alter the coagulation. - Use of combined hormonal contraceptives or hormone replacement therapy. - Hereditary coagulation disorders. - Refusal to give consent for participation in the study. INDIVIDUALS WITHOUT UC: - Under 18 years of age. - Advanced chronic disease or any other pathology that prevents the monitoring of the protocol of this study. - Pregnancy or lactation. - Alcohol or drug abuse. - Active infection with hepatitis B, C or HIV virus. - Finding of macroscopic alterations during the colonoscopy or finding of relevant inflammatory alterations in the biopsies obtained during the colonoscopy. -Treatment with immunomodulators, immunosuppressants, corticosteroids or other drugs that alter the immune system. - Medical history of thromboembolic events. -Treatment with anticoagulants, antiplatelets or other drugs that alter the coagulation. - Use of combined hormonal contraceptives or hormone replacement therapy. - Hereditary coagulation disorders. - Refusal to give consent for participation in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Study of platelet function [analysis of platelet activation (expression of surface markers PAC-1 and P-selectin) and platelet aggregation (percentage of maximum aggregation)] and clot formation kinetics using the ROTEM® technique [clotting time (seconds), clot formation time (seconds), angle a (degrees) and maximum clot strength (mm)] in peripheral blood samples from UC patients using an ex vivo approach (in the presence or absence of tofacitinib or anti-TNFa) and in vivo (in UC patients before and after initiation of tofacitinib or anti-TNFa treatment).;Timepoint(s) of evaluation of this end point: 12 months;Main Objective: - To study the ex vivo effect of tofacitinib on platelet function and coagulation in patients with UC.;Secondary Objective: - To evaluate the in vivo effect of tofacitinib on the procoagulant status (platelet function and coagulation) in patients with UC over time. - To determine if there is a specific effect of tofacitinib on haemostasis in UC patients treated with this drug compared with biological agents for UC. - To generate a collection of biological samples (serum, plasma, nucleic acids, RNA, stool and urine) from a cohort of patients with UC (before and after treatment with tofacitinib or anti-TNFa) that can be used for future complementary studies. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Determination of platelet activation: - Platelet activation status will be assessed ex vivo in platelet-rich plasma (PRP) samples from UC patients (active and quiescent) and healthy controls incubated in the absence or presence of drug (tofacitinib or anti-TNFa). Regarding the in vivo study, platelet activation will be analyzed in samples from patients with active UC before and after initiating treatment with tofacitinib or anti-TNFa. Platelet aggregation: - Platelet aggregation will be measured in PRP using a lumiaggregometer (Chrono-log Corporation, Havertown, PA, USA). In the case of the ex vivo study, PRP from UC patients (active and quiescent) and healthy controls will be incubated in the absence or presence of the different drugs (tofacitinib or anti-TNFa) and the results will be expressed as the percentage of maximum aggregation. Regarding the in vivo study, platelet aggregation will be analyzed in samples from patients with active UC before and after initiating treatment with tofacitinib or anti-TNFa. Clot formation study: - The procoagulant effect of tofacitinib in patients with UC will be evaluated ex vivo and in vivo using the rotational thromboelastometry technique (ROTEM®). For this purpose, the kinetics of clot formation will be studied using the INTEM test and the contribution of platelets to maximum clot firmness using the FIBTEM assay. For the ex vivo study, whole blood samples from UC patients (active and quiescent) and healthy controls incubated in the absence or presence of the different drugs (tofacitinib or anti-TNFa) will be incubated. As for the in vivo study, whole blood samples will be analyzed in patients with active UC before and after initiating treatment with tofacitinib or anti-TNFa. Endoscopic activity: - It will be evaluated by the Mayo endoscopic sub-score; endoscopic activity willbe considered as = 2. Endoscopic response: - It will be defined as a decrease of = 1 point in the Mayo endoscopic sub-score (6 | — |
Countries
Spain
Contacts
Public ContactSandra Hermida Vázquez
Hopsital Universitario de La Princesa
Outcome results
None listed