Von Willebrand Antigen and Activity as Novel Biomarkers of Hemostasis in Inflammatory Bowel Disease
NCT ID: NCT03715673
Last Updated: 2020-01-13
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
Recruitment Status
UNKNOWN
Total Enrollment
46 participants
Study Classification
OBSERVATIONAL
Study Start Date
2019-10-01
Study Completion Date
2020-12-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
The investigators are going to study von Willebrand antigen and activity levels in patients with inflammatory bowel disease. The study will be on 46 patients who were diagnosed with inflammatory bowel disease mainly ulcerative colitis and Crohn's disease divided into two arms; group A will include 23 cases with active IBD(cases)status and group B will include 23 cases with inactive IBD status(control) to compare the vWF antigen and activity ( expected to be higher in active disease group.
The investigators will follow all of the patients for any arterial or venous thrombosis to evaluate IBD as a risk factor of thrombosis, on the other hand, they are looking to detect cases of acquired von Willebrand syndrome in some cases with bleeding that not explained by the inflammatory bowel disease status.
The aim of the work:
1. Assessment of VWF antigen in patients with inflammatory bowel disease and correlate it to disease activity.
2. Evaluation of VWF antigen as a risk factor for thrombosis in inflammatory bowel disease patients.
3. Detection of acquired von Willebrand disease in inflammatory bowel disease.
The investigators will follow all of the patients for any arterial or venous thrombosis to evaluate IBD as a risk factor of thrombosis, on the other hand, they are looking to detect cases of acquired von Willebrand syndrome in some cases with bleeding that not explained by the inflammatory bowel disease status.
The aim of the work:
1. Assessment of VWF antigen in patients with inflammatory bowel disease and correlate it to disease activity.
2. Evaluation of VWF antigen as a risk factor for thrombosis in inflammatory bowel disease patients.
3. Detection of acquired von Willebrand disease in inflammatory bowel disease.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Coagulation Parameters in IBD Patients
NCT04115722
Coagulopathy
UNKNOWN
Novel Biomarkers in Inflammatory Bowel Disease
NCT03833310
Inflammatory Bowel Diseases
COMPLETED
Composite Ratios Boost CRP's Power in Monitoring Ulcerative Colitis.
NCT07261579
Ulcerative Colitis
COMPLETED
Clinical Characteristics and Risk Factors of Children Suffering From Inflammatory Bowel Diseases At Assiut University Children Hospital
NCT05002166
Inflammatory Bowel Disease
RECRUITING
Investigation of VAP-1 Expression and Tissue Blood Flow by PET-MRI in Patients With Crohn's Disease
NCT06555042
Crohn Disease
Inflammatory Bowel Diseases
Crohn Disease of Small Intestine
+3 more
RECRUITING
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
VWF is a high-molecular-weight multimeric glycoprotein, synthesized and released by vascular endothelial cells and megakaryocytes that play an important role in platelet-endothelial cell interaction and stabilizing the factor VIII (FVIII) coagulation protein.
Von Willebrand factor (VWF) is an acute-phase protein and a marker of endothelial damage.
VWF is crucial for platelet adhesion and aggregation. High-molecular weight multimers (HMWMs) are involved in platelet aggregation under high shear stress but under normal conditions it presents solely in the subendothelium and released into the bloodstream following activation of endothelial cells.
Coagulation and inflammation are simultaneously activated and respond in synergy as a preserved mechanism to repair the injured areas during tissue damage.
This observation is particularly relevant in acute inflammatory diseases, such as sepsis, but it also seems to be very important in chronic inflammatory conditions, such as inflammatory bowel disease.
Inflammatory bowel disease (IBD) with its two main forms, ulcerative colitis (UC) and Crohn disease (CD), is a chronic inflammatory condition characterized by local and systemic inflammation predominantly affecting the gastrointestinal tract and well known to be associated with a hypercoagulable state and subsequently with an increased risk for venous thromboembolism (VTE).
Thromboembolic complications such as Deep Venous Thrombosis (DVT) and Pulmonary Embolism (PE) represent amongst IBD complications an important and underestimated factor to be borne in mind which can significantly influence patient's morbidity and mortality.
In fact, according to the latest population-cohort studies, a 2 to 3-time fold increased risk of developing of thromboembolic complications was reported for IBD patients compared to general population.
In particular as Grainge., et al. and Papa., et al. both demonstrate in their studies, the incidence of thromboembolic events varies depending on the activity phase of the disease, suggesting that there is a higher risk of thromboembolic complications especially during IBD flares, with similar relative risk values for both Crohn's Disease and Ulcerative Colitis.
Although the causes of the increased risk of VTE in IBD are not yet completely understood, endothelial dysfunction has been demonstrated in IBD and it is evident through increasing levels of endothelial injury markers. The most frequently used biochemical markers of endothelial damage include von Willebrand factor (vWF), TM, vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1) and endothelin-1 (ET-1).
In 2017 Cibor et al published the first report of the effects of parameters associated with the structure and function of VWF on hemostasis in IBD. On the one hand, ADAMTS13: Ag was lower in IBD patients than in controls, particularly in subjects with UC; this resulted in an increased number of circulating multimers of VWF and thus an elevated thrombotic risk. The prothrombotic effects are enhanced by markedly elevated VWF: Ag.
On the other hand, the incidence of AVWS, which leads to an increased risk for bleeding, was higher in IBD patients. These findings provide insight into the elevated risk for thromboembolic events and bleeding observed in UC and less frequently in CD. The dysregulation of the balance between VWF function and ADAMTS13 reported herein might contribute to the complex hemostatic abnormalities observed in IBD.
Currently, the association between CD and AVWS is likely underestimated, especially in cases of acute bleeding not related to disease activity.
In 2017 Di Sabatino, et al reported three cases of IBD patients, who developed severe hemorrhagic manifestations due to the concomitant presence of an AVWS, in addition to other three cases was described in the literature. Such a condition can be life-threatening and its timely identification is mandatory to adopt the optimal therapeutic strategy.
The association between AVWS and IBD might be more frequent than expected. The autoimmune pathogenesis of IBD makes the association more likely. The availability of specialized coagulation centers and correlation with clinical information should confirm the diagnosis.
Methodology:
Patients will be subjected to the following:
Clinical assessment:
1. The clinical assessment will include demographic data, the presence of comorbidities, cigarette-smoking habits, previous history of thromboembolism and medications.
2. Body mass index (BMI) will be calculated for all patients.
3. In patients with CD and UC, the following parameters will be evaluated: disease duration, disease location, disease activity, complications, and past surgical procedures. Complications are defined as abscesses, fistulae, and stenoses.
4. Disease activity will be assessed according to ECCO-ESGAR Consensus Guidelines 2018.
Laboratory assessment:
The following will be done for all patients:
1. WBC, hematocrit, platelet count.
2. partial activated thromboplastin time.
3. C-reactive protein (CRP), and fecal calprotectin.
4. VWF: Ag, VWF: RCo and VWF: CB.
Radiological tests:
In cases with suspected arterial or venous thromboembolism, the appropriate radiological study will be done (i.e. venous doppler for deep venous thrombosis).
Von Willebrand factor (VWF) is an acute-phase protein and a marker of endothelial damage.
VWF is crucial for platelet adhesion and aggregation. High-molecular weight multimers (HMWMs) are involved in platelet aggregation under high shear stress but under normal conditions it presents solely in the subendothelium and released into the bloodstream following activation of endothelial cells.
Coagulation and inflammation are simultaneously activated and respond in synergy as a preserved mechanism to repair the injured areas during tissue damage.
This observation is particularly relevant in acute inflammatory diseases, such as sepsis, but it also seems to be very important in chronic inflammatory conditions, such as inflammatory bowel disease.
Inflammatory bowel disease (IBD) with its two main forms, ulcerative colitis (UC) and Crohn disease (CD), is a chronic inflammatory condition characterized by local and systemic inflammation predominantly affecting the gastrointestinal tract and well known to be associated with a hypercoagulable state and subsequently with an increased risk for venous thromboembolism (VTE).
Thromboembolic complications such as Deep Venous Thrombosis (DVT) and Pulmonary Embolism (PE) represent amongst IBD complications an important and underestimated factor to be borne in mind which can significantly influence patient's morbidity and mortality.
In fact, according to the latest population-cohort studies, a 2 to 3-time fold increased risk of developing of thromboembolic complications was reported for IBD patients compared to general population.
In particular as Grainge., et al. and Papa., et al. both demonstrate in their studies, the incidence of thromboembolic events varies depending on the activity phase of the disease, suggesting that there is a higher risk of thromboembolic complications especially during IBD flares, with similar relative risk values for both Crohn's Disease and Ulcerative Colitis.
Although the causes of the increased risk of VTE in IBD are not yet completely understood, endothelial dysfunction has been demonstrated in IBD and it is evident through increasing levels of endothelial injury markers. The most frequently used biochemical markers of endothelial damage include von Willebrand factor (vWF), TM, vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1) and endothelin-1 (ET-1).
In 2017 Cibor et al published the first report of the effects of parameters associated with the structure and function of VWF on hemostasis in IBD. On the one hand, ADAMTS13: Ag was lower in IBD patients than in controls, particularly in subjects with UC; this resulted in an increased number of circulating multimers of VWF and thus an elevated thrombotic risk. The prothrombotic effects are enhanced by markedly elevated VWF: Ag.
On the other hand, the incidence of AVWS, which leads to an increased risk for bleeding, was higher in IBD patients. These findings provide insight into the elevated risk for thromboembolic events and bleeding observed in UC and less frequently in CD. The dysregulation of the balance between VWF function and ADAMTS13 reported herein might contribute to the complex hemostatic abnormalities observed in IBD.
Currently, the association between CD and AVWS is likely underestimated, especially in cases of acute bleeding not related to disease activity.
In 2017 Di Sabatino, et al reported three cases of IBD patients, who developed severe hemorrhagic manifestations due to the concomitant presence of an AVWS, in addition to other three cases was described in the literature. Such a condition can be life-threatening and its timely identification is mandatory to adopt the optimal therapeutic strategy.
The association between AVWS and IBD might be more frequent than expected. The autoimmune pathogenesis of IBD makes the association more likely. The availability of specialized coagulation centers and correlation with clinical information should confirm the diagnosis.
Methodology:
Patients will be subjected to the following:
Clinical assessment:
1. The clinical assessment will include demographic data, the presence of comorbidities, cigarette-smoking habits, previous history of thromboembolism and medications.
2. Body mass index (BMI) will be calculated for all patients.
3. In patients with CD and UC, the following parameters will be evaluated: disease duration, disease location, disease activity, complications, and past surgical procedures. Complications are defined as abscesses, fistulae, and stenoses.
4. Disease activity will be assessed according to ECCO-ESGAR Consensus Guidelines 2018.
Laboratory assessment:
The following will be done for all patients:
1. WBC, hematocrit, platelet count.
2. partial activated thromboplastin time.
3. C-reactive protein (CRP), and fecal calprotectin.
4. VWF: Ag, VWF: RCo and VWF: CB.
Radiological tests:
In cases with suspected arterial or venous thromboembolism, the appropriate radiological study will be done (i.e. venous doppler for deep venous thrombosis).
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Inflammatory Bowel Diseases
Von Willebrand Diseases
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
Observational Model Type
CASE_CONTROL
Study Time Perspective
PROSPECTIVE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Cases:Active IBD patients
23 patients with active inflammatory bowel disease for whom von willlebrand antigen and activity will be done
von willebrand antigen and activity
Intervention Type
DIAGNOSTIC_TEST
Measuring von Willebrand antigen and activity (VWF: RCo and VWF: CB)
Control:Inactive IBD patients
23 patients with inactive inflammatory bowel disease; VWF antigen and activity will be done for them
von willebrand antigen and activity
Intervention Type
DIAGNOSTIC_TEST
Measuring von Willebrand antigen and activity (VWF: RCo and VWF: CB)
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
von willebrand antigen and activity
Measuring von Willebrand antigen and activity (VWF: RCo and VWF: CB)
Intervention Type
DIAGNOSTIC_TEST
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
•Patients with inflammatory bowel disease either newly or previously diagnosed aged18 years and older.
Exclusion Criteria
* Pregnancy.
* Myocardial infarction.
* Stroke.
* Thromboembolism.
* Known hemorrhagic diathesis.
* Cancer.
* Renal insufficiency.
* Liver injury.
* Diabetes.
* patients who are on aspirin, heparin, oral anticoagulants, or oral contraceptives pills.
* Myocardial infarction.
* Stroke.
* Thromboembolism.
* Known hemorrhagic diathesis.
* Cancer.
* Renal insufficiency.
* Liver injury.
* Diabetes.
* patients who are on aspirin, heparin, oral anticoagulants, or oral contraceptives pills.
Minimum Eligible Age
18 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Assiut University
OTHER
Sponsor Role
lead
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Alaa Mohammed Abozied Abdallah
clinical hematology specialist
Responsibility Role
PRINCIPAL_INVESTIGATOR
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Assiut University
Asyut, , Egypt
Site Status
RECRUITING
Countries
Review the countries where the study has at least one active or historical site.
Egypt
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
References
Explore related publications, articles, or registry entries linked to this study.
Yee A, Kretz CA. Von Willebrand factor: form for function. Semin Thromb Hemost. 2014 Feb;40(1):17-27. doi: 10.1055/s-0033-1363155. Epub 2013 Dec 13.
Reference Type
BACKGROUND
Cibor D, Domagala-Rodacka R, Rodacki T, Jurczyszyn A, Mach T, Owczarek D. Endothelial dysfunction in inflammatory bowel diseases: Pathogenesis, assessment and implications. World J Gastroenterol. 2016 Jan 21;22(3):1067-77. doi: 10.3748/wjg.v22.i3.1067.
Reference Type
BACKGROUND
Reininger AJ. The function of ultra-large von Willebrand factor multimers in high shear flow controlled by ADAMTS13. Hamostaseologie. 2015;35(3):225-33. doi: 10.5482/HAMO-14-12-0077. Epub 2015 May 18.
Reference Type
BACKGROUND
Lipinski S, Bremer L, Lammers T, Thieme F, Schreiber S, Rosenstiel P. Coagulation and inflammation. Molecular insights and diagnostic implications. Hamostaseologie. 2011 May 2;31(2):94-102, 104. doi: 10.5482/ha-1134. Epub 2010 Dec 9.
Reference Type
BACKGROUND
Esmon CT. The interactions between inflammation and coagulation. Br J Haematol. 2005 Nov;131(4):417-30. doi: 10.1111/j.1365-2141.2005.05753.x.
Reference Type
BACKGROUND
Owczarek D, Cibor D, Glowacki MK, Rodacki T, Mach T. Inflammatory bowel disease: epidemiology, pathology and risk factors for hypercoagulability. World J Gastroenterol. 2014 Jan 7;20(1):53-63. doi: 10.3748/wjg.v20.i1.53.
Reference Type
BACKGROUND
Arora Z, Wu X, Navaneethan U, Shen B. Non-surgical porto-mesenteric vein thrombosis is associated with worse long-term outcomes in inflammatory bowel diseases. Gastroenterol Rep (Oxf). 2016 Aug;4(3):210-5. doi: 10.1093/gastro/gov012. Epub 2015 Apr 28.
Reference Type
BACKGROUND
Bollen L, Vande Casteele N, Peeters M, Van Assche G, Ferrante M, Van Moerkercke W, Declerck P, Vermeire S, Gils A. The Occurrence of Thrombosis in Inflammatory Bowel Disease Is Reflected in the Clot Lysis Profile. Inflamm Bowel Dis. 2015 Nov;21(11):2540-8. doi: 10.1097/MIB.0000000000000531.
Reference Type
BACKGROUND
Grainge MJ, West J, Card TR. Venous thromboembolism during active disease and remission in inflammatory bowel disease: a cohort study. Lancet. 2010 Feb 20;375(9715):657-63. doi: 10.1016/S0140-6736(09)61963-2. Epub 2010 Feb 8.
Reference Type
BACKGROUND
Papa A, Gerardi V, Marzo M, Felice C, Rapaccini GL, Gasbarrini A. Venous thromboembolism in patients with inflammatory bowel disease: focus on prevention and treatment. World J Gastroenterol. 2014 Mar 28;20(12):3173-9. doi: 10.3748/wjg.v20.i12.3173.
Reference Type
BACKGROUND
Cromer WE, Mathis JM, Granger DN, Chaitanya GV, Alexander JS. Role of the endothelium in inflammatory bowel diseases. World J Gastroenterol. 2011 Feb 7;17(5):578-93. doi: 10.3748/wjg.v17.i5.578.
Reference Type
BACKGROUND
Cibor D, Owczarek D, Butenas S, Salapa K, Mach T, Undas A. Levels and activities of von Willebrand factor and metalloproteinase with thrombospondin type-1 motif, number 13 in inflammatory bowel diseases. World J Gastroenterol. 2017 Jul 14;23(26):4796-4805. doi: 10.3748/wjg.v23.i26.4796.
Reference Type
BACKGROUND
Di Sabatino A, Ambaglio C, Aronico N, Ghidelli N, Lenti MV, Gamba G, Corazza GR. Acquired von Willebrand syndrome in inflammatory bowel disease. Haemophilia. 2017 May;23(3):e231-e233. doi: 10.1111/hae.13209. Epub 2017 Mar 17. No abstract available.
Reference Type
BACKGROUND
Federici AB, Budde U, Castaman G, Rand JH, Tiede A. Current diagnostic and therapeutic approaches to patients with acquired von Willebrand syndrome: a 2013 update. Semin Thromb Hemost. 2013 Mar;39(2):191-201. doi: 10.1055/s-0033-1334867. Epub 2013 Feb 8.
Reference Type
BACKGROUND
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
vWF in IBD
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.
Hematological Indices and Fecal Calprotectin Predict Histological Remission in Ulcerative Colitis
NCT04818788
UNKNOWN
Value Of ACE Index (Albumin, CRP And Endoscopy) In Predicting Intra Venous Steroid Response In Acute Severe Ulcerative Colitis In Assiut University Hospitals
NCT06267651
NOT_YET_RECRUITING
Inherited Thromophilia and Thrombotic Risks in Inflammatory Bowel Disease During Activity and Remission
NCT06691451
NOT_YET_RECRUITING
Role of the Chemical Environment in the Pathogenesis of Inflammatory Bowel Disease
NCT03376230
TERMINATED
Anti CT-P13 Antibody in Moderate to Severe Inflammatory Bowel Disease
NCT02846961
COMPLETED
Biologics in Management of Inflammatory Bowel Disease in Egyptian Patients
NCT05720221
COMPLETED
Platelet Indices in Inflammatory Bowel Diseases
NCT07320443
NOT_YET_RECRUITING
Biological Therapy in Patients With Inflammatory Bowel Disease
NCT05599867
UNKNOWN
Cytokines and Genes in Therapeutic Response in Crohn's Disease
NCT03266471
COMPLETED
68Ga-FAPI-46 PET/CT for Assessing Small Bowel Fibrostenosis in Crohn's Disease
NCT07273188
NOT_YET_RECRUITING
EARLY_PHASE1
Delayed Diagnostic Time& Inflammatory Bowel Diseased Patients
NCT04952558
UNKNOWN
Neutrophil to Lymphocyte Ratio in Inflammatory Bowel Disease
NCT04558658
UNKNOWN
Role of C-Reactive Protein /Albumin Ratio in Evaluation of Disease Activity in Patients With Inflammatory Bowel Disease
NCT05738915
UNKNOWN
Evaluation of Blood Platelet Indices,Platelet Aggregation in the Activity of IBD Patients on Biological Treatment
NCT05406934
UNKNOWN
Study of Inflammatory Markers (VNN1) in Crohn Disease and Ulcerative Colitis.
NCT02304666
UNKNOWN
NA
Hypercoagulability Study Using Haemostatic Techniques in Patients With Inflammatory Bowel Disease
NCT04896203
UNKNOWN
Vitamin D Status in Inflammatory Bowel Disease
NCT03496246
UNKNOWN
NA
Biomarkers of Intestinal Fibrosis in Small Bowel Crohn's Disease
NCT04088773
ACTIVE_NOT_RECRUITING
Open-label V565 Target Engagement Study
NCT03705117
COMPLETED
PHASE1
Serum Lactate and Ulcerative Colitis
NCT05876494
UNKNOWN
Magnetic Resonance Enterography in Inflammatory Bowel Diseases
NCT04324632
UNKNOWN
Fluorescence Imaging of Adalimumab-680LT in Inflammatory Bowel Disease
NCT06117423
RECRUITING
PHASE1/PHASE2
Evaluation of a New Oral Contrast Agent for MR Enterography in the Assessment of Crohn Disease in the Small Bowel
NCT00587210
COMPLETED
Fluorescence Imaging of Adalimumab-680LT and Risankizumab-800CW in Inflammatory Bowel Disease
NCT07258641
NOT_YET_RECRUITING
PHASE1/PHASE2