Phase I, II and III Trials in Inflammatory Bowel Diseases: A Practical Guide for the Non-specialist

2020 ◽  
Vol 14 (5) ◽  
pp. 710-718 ◽  
Author(s):  
Ferdinando D’Amico ◽  
Cedric Baumann ◽  
Hélène Rousseau ◽  
Silvio Danese ◽  
Laurent Peyrin-Biroulet
Keyword(s):  
Clinical Trial ◽  
Data Analysis ◽  
Inflammatory Bowel Diseases ◽  
Control Group ◽  
Patient Stratification ◽  
Clinical Phase ◽  
New Drug ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Design Type

Abstract In the last few decades several new molecules have been developed in the field of inflammatory bowel diseases. However, the process that leads to the approval and use of a new drug is very long, expensive and complex, consisting of various phases. There is a pre-clinical phase that is performed on animals and a clinical phase that is directed to humans. Each research phase aims to evaluate different aspects of the drug and involves a specific target group of subjects. In addition, many aspects must be considered in the evaluation of a clinical trial: randomization, presence of a control group, blind design, type of data analysis performed, and patient stratification. The objective of this review is to provide an overview of the clinical trial phases of a new drug in order to better understand and interpret their results.

scholarly journals Biological therapy and surgery rates in inflammatory bowel diseases – Data analysis of almost 1000 patients from a Hungarian tertiary IBD center

PLoS ONE ◽  
2018 ◽  
Vol 13 (7) ◽  
pp. e0200824 ◽  
Author(s):  
Kata Szántó ◽  
Tibor Nyári ◽  
Anita Bálint ◽  
Renáta Bor ◽  
Ágnes Milassin ◽  
...  
Keyword(s):  
Data Analysis ◽  
Inflammatory Bowel Diseases ◽  
Biological Therapy ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Surgery Rates

scholarly journals The Prevalence of Adherent-Invasive Escherichia coli and Its Association With Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Razie Kamali Dolatabadi ◽  
Awat Feizi ◽  
Mehrdad Halaji ◽  
Hossein Fazeli ◽  
Peyman Adibi
Keyword(s):  
Escherichia Coli ◽  
Systematic Review ◽  
Inflammatory Bowel Diseases ◽  
Meta Analysis ◽  
Control Group ◽  
Pooled Prevalence ◽  
Bowel Diseases ◽  
Phylogenetic Grouping ◽  
Inflammatory Bowel ◽  
And Control

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are known as chronic gastrointestinal inflammatory disorders. The present systematic review and meta analysis was conducted to estimate the prevalence of adherent-invasive Escherichia coli (AIEC) isolates and their phylogenetic grouping among IBD patients compared with the controls. A systematic literature search was conducted among published papers by international authors until April 30, 2020 in Web of Science, Scopus, EMBASE, and PubMed databases. The pooled prevalence of AIEC isolates and their phylogenetic grouping among IBD patients as well as in controls was estimated using fixed or random effects models. Furthermore, for estimating the association of colonization by AIEC with IBD, odds ratio along with 95% confidence interval was reported. A total of 205 articles retrieved by the initial search of databases, 13 case–control studies met the eligibility criteria for inclusion in the meta analysis. There were 465 IBD cases (348 CD and 117 UC) and 307 controls. The pooled prevalence of AIEC isolates were 28% (95% CI: 18–39%), 29% (95% CI: 20–40%), 13% (95% CI: 1–30%), and 9% (95% CI: 3–19%), respectively among IBD, CD, UC, and control group, respectively. Our results revealed that the most frequent AIEC phylogroup in the IBD, CD, and control groups was B2. Fixed-effects meta analysis showed that colonization of AIEC is significantly associated with IBD (OR: 2.93; 95% CI: 1.90–4.52; P < 0.001) and CD (OR: 3.07; 95% CI: 1.99–4.74; P < 0.001), but not with UC (OR: 2.29; 95% CI: 0.81–6.51; P = 0.11). In summary, this meta analysis revealed that colonization by AIEC is more frequent in IBD and is associated with IBD (CD and UC). Our results suggested that the affects of IBD in patients colonized with the AIEC pathovar is not random, it is in fact a specific disease-related pathovar.

scholarly journals DIAGNOSTIC VALUE OF INTERLEUKIN-6 AND D-DIMER IN INFLAMMATORY BOWEL DISEASES

2021 ◽  
pp. 92-96
Author(s):  
А. P. Lutsyk ◽  
D. V. Shorikova
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Interleukin 6 ◽  
Roc Analysis ◽  
Diagnostic Value ◽  
Control Group ◽  
Active Process ◽  
Montreal Classification ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
D Dimer

The article deals with the diagnostic value of changes in the content of interleukin-6 and D-dimer in patients with inflammatory bowel diseases (IBD) - Ulcerative Colitis (UC) and Crohn Disease (CD). Materials and methods: We have studied 34 patients with UC and 18 people with CD with continuously recurrent course. There are also analysed data of 15 patients with UC and 15 patients with CD in period of the remission. The control group included 30 healthy volunteers. Clinical, endoscopic examination, an immunoassay determination of the content of interleukin-6 (IL-6) and D-dimer, was carried out. CD activity was assessed using the Chron’s disease activity index. The localization of CD was established according to the Montreal classification. The clinical activity of the disease in patients with UC was determined using the classification according to Truelove-Witts. The value of the index consisted of the sum of points for each indicator, which allowed determining the activity of the inflammatory process. Statistical processing was performed using STATISTICA 10.0 (StatSoft. Inc., USA), at p<0.05, the discrepancies between the obtained data were considered statistically significant. Research results. According to the obtained data, mild activity was found in 7 patients with UC (20.6%) and 4 - with CD (22.3%), moderate severity - in 17 (50.0%) and 8 (44.4%) patients, severe - in 10 (29.4%) and 6 (33.3%) patients. In the remission stage, 15 patients with UC and 15 patients with CD were examined. According to the Montreal classification, lesions of the upper gastrointestinal tract (L4) were observed in 4 patients with CD (22.2%), terminal ileitis (L1) occurred in 10 patients (55.6%), 4 patients were diagnosed with ileocolitis (L3) - 22.2%. It has been established that patients with an active course of UC and CD had a higher level of proinflammatory markers and thrombosis markers (D-dimer and IL-6) compared with inactive course and control group (p<0.05). The D-dimer content in UC was 690±315 pg/l. It is confirmed the increase of the content of this marker in 2.55 times compared to control group and in 1.43 times than inactive course of the disease respectively. The level of IL-6 at active in course of UC was 3.36±1.78 pg/ml, increasing in 2.07 times against control and in 1.72 times compared with group of remission. In the active course of CD, the level of D-dimer reached 720±267 pg/ml, increasing in 2.67 times in relation to control and in 1.60 times with respect to patients under remission. The content of IL-6 in the active course of CD reached 4.07±2.17 pg/ml, increasing in 2.85 times in comparison to healthy individuals and in 2.83 times relatively patients with remission. While using the ROC-analysis, the most sensitive value as a “cut point” for the diagnosis of the active process in the course of IBD can be considered the content of the D-dimer in an amount of more than 650 pg/l. The calculated AUC in ROC-analysis for the IL-6 content was 73.7%±6.14% (61.7 - 85.7, p<0.001), indicating the prognostic value of the model. The values of the IL-6 content of more than 2.80 pg/ml are diagnostically significant to predict the active process in IBD.

scholarly journals N10 Effectiveness of self-management workshop in inflammatory bowel diseases according to psychosocial profiles. Clinical trial

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S661-S662
Author(s):  
A Rivera Sequeiros ◽  
Y Torres Dominguez ◽  
M Á ◽  
Izquierdo Macías ◽  
M V Ruiz Romero
Keyword(s):  
Quality Of Life ◽  
Social Support ◽  
Clinical Trial ◽  
Inflammatory Bowel Diseases ◽  
Self Management ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Management Workshop ◽  
Psychosocial Profiles

Abstract Background The main objective in the management of chronic diseases is to maintain and improve the quality of life. In this sense, the involvement of the patient in their self-care should be a priority for nursing, but we know that the results are not always the desired ones. Self-care education and training should focus on social and emotional aspects, identified as predictors of the deterioration of the quality of life. Studies have identified psychosocial profiles (Controlled, Reinforced, Weak, Fragile) of patients with inflammatory bowel diseases (IBD) based on their level of social support and emotional coping. These profiles could predict the effectiveness of these educational workshops. This study aims to compare the effectiveness of a self-management workshop in different patient profiles to identify what type of patient might benefit and which don’t. Methods Non-randomised clinical trial. 61 outpatients were included. Inclusion criteria: Have IBD, be over 18 years old and sign the informed consent. They were included in a self-management training programme to learn about the disease and coping. There were 4 sessions in a month. They completed a questionnaire before the workshop, at the end of the workshop, at 3 months and at 6 months. The variables were sociodemographic, clinical, quality of life, coping, perceived stress, social support and anxiety-depression. Results The characteristics of the sample are shown in Table 1. The four psychosocial profiles described in the literature were identified and the effectiveness of the workshop in each one was analysed. The intrasubject linear analysis showed a linear type increase in the quality of life of patients with Reinforced and Weakening profile, between baseline and third month (−3.81, p = 0.036, CI: (− 7.45; −0.17) and − 6.21, p = 0.004, CI: (− 11.08; −1.35) respectively). The observed power was 91.5% and 93.8% for each case. However, no significant differences were found in patients with Controlled profile and Fragiles. The results found were not associated with other variables of the study. Conclusion Identifying psychosocial profiles allows us to succeed with the type of education we offer to patients. We must customise the information and resources. In the case of patients with a great lack of family support, one would first have to intervene with the family and then offer emotional education and not vice versa.

scholarly journals On-Treatment Decrease of Serum Interleukin-6 as a Predictor of Clinical Response to Biologic Therapy in Patients with Inflammatory Bowel Diseases

2020 ◽  
Vol 9 (3) ◽  
pp. 800 ◽  
Author(s):  
Gian Caviglia ◽  
Chiara Rosso ◽  
Francesco Stalla ◽  
Martina Rizzo ◽  
Alessandro Massano ◽  
...  
Keyword(s):  
Clinical Response ◽  
Inflammatory Bowel Diseases ◽  
Biologic Therapy ◽  
Multivariate Logistic Regression Analysis ◽  
Response To Treatment ◽  
Control Group ◽  
Biologic Treatment ◽  
Necrosis Factor Alpha ◽  
Bowel Diseases ◽  
Inflammatory Bowel

In patients with inflammatory bowel diseases (IBD) undergoing biologic therapy, biomarkers of treatment response are still scarce. This study aimed to evaluate whether serum zonulin, a biomarker of intestinal permeability; soluble CD163 (sCD163), a macrophage activation marker; and a panel of serum cytokines could predict the response to biologic treatment in patients with IBD. For this purpose, we prospectively enrolled 101 patients with IBD and 19 patients with irritable bowel syndrome (IBS) as a control group; 60 out of 101 patients underwent treatment with biologics. Zonulin, sCD163, and cytokines were measured at the baseline in all patients and after 10 weeks of treatment in the 60 patients who underwent biologic therapy. We observed that zonulin levels were higher in IBD patients with active disease compared to those in remission (p = 0.035), and that sCD163 values were higher in patients with IBD compared to those with IBS (p = 0.042), but no association with therapy response was observed for either biomarker. Conversely, interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor-alpha showed a significant reduction from baseline to week 10 of treatment, particularly in responder patients. By multivariate logistic regression analysis corrected for disease (Crohn’s disease or ulcerative colitis), type of biologic drug (Infliximab, Adalimumab, Vedolizumab, or Ustekinumab) and disease activity, the reduction in IL-6 values was associated with a clinical response at 12 months of biological therapy (odds ratio (OR) = 4.75, 95% confidence interval (CI) 1.25–18.02, p = 0.022). In conclusion, the measurement of serum IL-6 in biologics-treated IBD patients may allow for the prediction of response to treatment at 12 months of therapy and thus may help with tailoring personalized treatment strategies.

Clinico-pathological profile evaluation in patients affected by chronic inflammatory bowel diseases

2017 ◽  
Vol 41 (S1) ◽  
pp. S320-S320
Author(s):  
F. Travagliati ◽  
E. Borrelli ◽  
S. Martinelli ◽  
L. Dattoli ◽  
D. Ferrarese ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Self Efficacy ◽  
Social Impact ◽  
Anxiety And Depression ◽  
Control Group ◽  
Psychological Wellness ◽  
Bowel Diseases ◽  
Chron's Disease ◽  
Inflammatory Bowel ◽  
Competing Interest

IntroductionInflammatory bowel diseases (IBDs) have high social impact. Aetiology is still unknown, however multifactorial genesis is surely implicated. We tried to correlate IBDs and psychological distress through evaluated psychometrical instruments and subsequently to relate subjective influences with gastroenteric clinical manifestation, defining new critical elements on which IBD are based.MethodsIn our study, we included 57 participants, selected according to their diagnosis, between those attending our gastrointestinal ambulatory: 26 had Chron's disease, while 31 had ulcerative colitis. 78 people without gastroenteric or psychiatric disorder were also included in the study as control group. Psychometric questionnaires were administered to evaluate anxiety and depressive symptoms, quality of live, self-efficacy and resilience (Fig. 1).ResultsLevels of anxiety and depression were higher in patients with IBDs than in the control group. STAI-Y highlighted higher state anxiety and trait anxiety levels in first group. HADS showed higher scores in ill patients, as well as CD-RISC showed a more impaired resilience. EQ-VAS, PGWBI and GSE revealed significant differences in health status, psychological wellness and self-efficacy between the two groups.ConclusionsIBDs seem related to psychological diseases. Affected patients have higher anxiety and depression levels than general population as well as lower self-efficacy and resilience. Those elements being strictly linked to physical discomfort contributes to develop a loop in which patients get caught. Creating a model of integrated cooperation between gastroenterologist and psychiatrist during treatment of patients with IBDs seems fundamental to grant at once all the professional figures each patient needs for better care.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals The cardiovascular system in patients with functional and inflammatory bowel diseases

2018 ◽  
Vol 90 (2) ◽  
pp. 59-64
Author(s):  
I V Maev ◽  
A N Kazulin ◽  
D N Andreev
Keyword(s):  
Right Ventricle ◽  
Cardiovascular System ◽  
Inflammatory Bowel Diseases ◽  
Right Atrium ◽  
Systolic Pressure ◽  
Clinical Manifestations ◽  
Control Group ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
The Right

Aim. Identification of subclinical and metamanifests state changes of cardiovascular system in patients with functional and inflammatory bowel diseases (IBD) without a background of cardiac pathology. Materials and methods. Was examined 79 patients with colon diseases, 20 patients were diagnosed with irritable bowel syndrome (IBS) with diarrhea, 37 - with undifferentiated colitis (UdC) and 22 patients with ulcerative colitis (UC). As a control group were examined in 50 healthy subjects. All patients received treatment in accordance with international and national guidelines. Prescribed medications had effect on the function of the cardiovascular system. Patients with contacting the hospital and against the onset of remission was performed ultrasound of the heart. Determines the size of the left atrium, heart rate, end-diastolic volume, end-systolic volume, ejection fraction (EF), cardiac index (CI), total peripheral vascular resistance, the presence of right heart failure, blood flow, the area of the right atrium and right ventricle in systole and diastole, and calculated the proportion of contractility of the right atrium and right ventricle. Determined systolic pressure in PA (SPPA), the average pressure in PA (APPA). Results. Clinical manifestations of cardiac syndrome was identified in 75,0% of patients with IBS, 54,1% of patients NK and 68,2% patients with UC. When performing correlation analysis in the patients with UdC and UC was noted the relationship of hemodynamic parameters and disease severity was more pronounced in UC. So, when comparing the duration of the disease and levels of the MLC - r=0,52 and r=0,73 (p

scholarly journals THE ROLE OF ENDOTHELIAL DYSFUNCTION IN INFLAMMATORY BOWEL DISEASES

2021 ◽  
Vol 20 (2) ◽  
Author(s):  
A.P. Lutsyk ◽  
E.I. Shorikov
Keyword(s):  
Endothelial Dysfunction ◽  
Inflammatory Bowel Diseases ◽  
Inactive Disease ◽  
Control Group ◽  
Endothelium Dysfunction ◽  
Mild Degree ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Index Level ◽  
Severe Degree

The purpose of the study – to assess the disorders’ degree of endothelium dysfunction inpatients with nonspecific ulcerative colitis (NUC) and Crohn's disease (CD), dependingon the severity of inflammation.Material and methods. 34 patients with NUC and 18 people with CD with continuousrecurrent courses, 15 patients with NUC and 15 patients with CD in remission wereobserved. The control group included 30 healthy volunteers.Results. It has been established that patients with active NUC had a significantly higherlevel of markers characterizing changes of proliferative (VEGF-165) and adhesive(VCAM-1) endothelial functions vs. control (in 4.62 and 2.01 times) and patients whohad an inactive disease (at 3.95 and 4.62) (p<0.05). In the active course of NUC, VEGF-165 level increased by 3.27 and 5.03 times, the level of VCAM by 1.83 and 2.09 times vs.inactive and control group (p<0.05).In patients with severe and moderate degrees of NUC, we have set an increase in theconcentration of VEGF-165 compared with mild degree, p<0.05. It has been proven thatin severe degree of CD, the concentration of VEGF-165 increased 21.5% vs. moderateactivity and 63.1% vs. mild activity, p<0.05.It has been established that adhesive phenotype of endothelial dysfunction with severeactivity of NUC was associated with an elevated content of adhesion molecule, dependingof activity, p<0.05. The adhesive phenotype of endothelial dysfunction is proved forpatients with severe activity of CD compared with moderate and mild activity, p<0.05.We have revealed a reliable direct regression relationship between the concentration ofthe vascular endothelial growth factor and the activity of UC according to the TrueloveWitts scale (R=0.29, p<0.05), between the CDAI index level in CD and the content ofVCAM-1 (R=0.29, p<0.05).Conclusions. Inflammatory bowel diseases - NUC and CD are accompanied withendothelium dysfunction, proliferative and adhesive phenotypes, associated with theactivity of process.

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