Symptoms and General Pathology

All Conditions

Skin and Connective Tissue Diseases

Immune System Diseases

Rare Diseases

Necrosis

Pemphigoid, Bullous

Blister

Skin Diseases

Skin Diseases, Vesiculobullous

Autoimmune Diseases

Pathological Conditions, Anatomical

Bullous Pemphigoid

All Drugs and Chemicals

Antibodies

Immunoglobulins

Immunoglobulins, Intravenous

Eosinophil Cationic Protein

Bullae and blood serum, which are obtained before and under treatment, will be compared in each other regardless of any condition.

Mehmet Salih Gurel, Professor

This study investigates the differences of Eosinophil Cationic Protein, Tumor Necrosis Factor-alpha and Anti-BP180-NC16A IgG levels of blister fluids in Bullous Pemphigoid patients which appeared before and under treatment subsequently. These molecules will also be measured in blood serum before and under treatment. Changes of titers in serum and differences between blister fluids will be compared to observe whether correlation exists between them. These measures will also be compared between groups of responders and non-responders to the first-line treatment options to analyze correlation with treatment success.

Bullous Pemphigoid is an auto-immune bullous disorder in which auto-antibodies to hemidesmosomes, complement pathway, inflammatory cells and mediators play a crucial roles for disease pathogenesis.

Anti-BP180-NC16A IgG is an antibody that it primarily triggers inflammatory reactions and complement cascade in bullae development and plays major roles in disease pathogenesis. It is secreted by plasma cells which is induced by T-helper 2 cells and their cytokines in serum and lesional tissue. Anti-BP180 antibody detection in serum is very important in diagnosis and titers correlate with disease activity. Anti-BP180 antibody can also be detected in blister fluids and it may aid diagnosis.

Eosinophil cationic Protein is a cytokine and secreted by Eosinophil which is found in abundant numbers and correlated with tissue damage in Bullous Pemphigoid lesions. Serum titers of Eosinophil Cationic Protein has a correlation with disease activity and it is higher in blister fluid than serum. Tumor Necrosis Factor-alpha is an another cytokine which is secreted from inflammatory cells initially after inflammatory cascade is triggered. It is also found increased in serum blister fluids. Tumor necrosis factor-alpha is associated with clinical severity in bullous pemphigoid.

In Bullous Pemphigoid, development of bulla is required to be stopped if treatment will be considered as successful. Nevertheless smaller, more rapidly healing vesicles and bullae appear under treatment which are not regarded as findings of treatment failure. In this study we will measure Eosinophil Cationic Protein, Tumor Necrosis Factor-alpha and Anti-BP180-NC16A IgG levels with E.L.I.S.A. technique in these subsequently appeared blisters if they will appear and compare them with pretreatment blisters. We will also measure levels of these molecules in blood serum before and under treatment. We will analyze corralation between blood serum and blister fluids. Also we will compare responder patients and non-responder patients to first-line treatment options to observe correlation of changes and differences in these body fluids with treatment success.

Blister Fluid: Blister fluids will be obtained from all enrolled patients in specific three intervals: Before treatment, 4-7. and 8-14. days of treatment in 24 hours after they appear.

Bullae of only one individual day will be selected for each interval to study if they appeared.

Blood Serum: Blood serum will be obtained from all enrolled patients before treatment, seventh day of treatment and fourteen day of treatment.

Obtaining blood serum from patients was added to study afterward. New ethical committee approval was received for that modification in recruitment status at May 17, 2018. Thus blood serum weren't obtained patients who were recruited before that approval. But other specimens obtained from these patients will be included study.

Cytokines in Blister Fluids of Bullous Pemphigoid (BP)

Evaluation of Cytokines and Immunoglobulins in Serum and Blister Fluids Appeared Before Treatment and Subsequently Under Treatment in Bullous Pemphigoid

Calculated of measurements of Eosinophil Cationic Protein (pg/ml) by ELISA technique in blister fluids and serums that obtained before treatment and under first and second weeks of treatment.

Calculated of measurements of Tumor Necrosis Factor-alpha (pg/ml) by ELISA technique in blister fluids and serums that obtained before treatment and under first and second weeks of treatment.

Calculated of measurements of Anti-BP180-NC18A IgG (U/ml) by ELISA technique in blister fluids and serums that obtained before treatment and under first and second weeks of treatment.

Time interval between initiation of treatment and control of disease activity/beginning of consolidation phase

Time interval between control of disease activity and end of consolidation phase.

Development of nontransient lesions that heal in more than one week, continued extension of old lesions, failure of established lesions to begin to heal or continued pruritus despite of Treatment of one month.

Appearance of more than three lesions per month or at least one large eczematous lesion or urticarial plaques that do not heal within one week, or extension of established lesions or daily pruritus in patient who was achieved disease control

This assessment will depend on multiple factors according to more than one classification. Patients will be separated to mild, moderate, severe conditions according to their clinical findings.

Mild: Involvement of less than %10 of skin surface area and appearance of less than 10 bullae in each day. Both feature will be necessary to regard individual patient's disease as mild.

Moderate: Involvement of %10-30 of skin surface area and appearance of less than 10 bullae in each day. Both feature will be necessary to regard individual patient's disease as moderate.

Severe: Involvement of more than %30 of skin surface area or appearance of more than 10 bullae in each day or B.P.D.A.I. score more than 56 (without Visual analogue score of pruritus). Existence of even one of this findings will ve sufficient to regard individual patient's disease as severe.

BPDAI is an index to assess disease area and severity depending on involvement of mucosa and skin region, lesion number and size. Minimum score is 0 and maximum score is 360.

This index will be calculated at before treatment, second week and fourth week of treatment. After first month it will be calculated in each follow-up visit.

Scars of previous lesions are also included to this index, minimum score is 0 and maximum score is 12.

This index will be calculated at before treatment, second week and fourth week of treatment. After first month it will be calculated in each follow-up visit.

Visual analogue score of pruritus is also part of this index. Minimum score is 0 and maximum score is 10. This score will be assessed for last 24 hours, last one week, last one month one by one; thus maximum score will be 30.

This index will be calculated at before treatment, second week and fourth week of treatment. After first month it will be calculated in each follow-up visit.

Mahmut Can Koska

Assistant Doctor

Digestive System Diseases

Inflammation

Inflammatory Bowel Diseases

Intestinal Diseases

Gastrointestinal Diseases

Gastroenteritis

screening every 3rd month: (home monitoring: FC and DA)

screening On demand: (home monitoring: FC and DA)

Home monitoring is a supportive treatment. Patients are randomized to screen themselves on demand

At Home Screening procedure On demand

Home monitoring is a supportive treatment. Patients are randomized to screen themselves every 3 months

At Home Screening procedure every 3 months

Pia Munkholm, Professor

This study is a side protocol/extension of 10 years of ClinicalTrials.gov ID: NCT02492555. The purpose of this study is to determine if the IBD patients doing home monitoring (screening themselves on demand (OD) or every 3 months) have relative reduced rates of colectomies, resections, mortalities and cancer after 11 years of web monitoring. The IBD patients are self-monitoring by web apps consisting of a short disease activity questionnaire (DA) and fecal calprotectin (FC) on any smart phone.

This study is a side protocol/extension of 10 years of ClinicalTrials.gov ID: NCT02492555. Among 2.500 IBD patients the investigators have consecutively from the Gastroenterology out-patient clinic at North Zealand University Hospital recruited in total 120 in the study.

At the out-patient consultation IBD patients has been informed about the project and the IBD eHealth nurse has ensured that no exclusion criteria was met by the patients.

Inclusion criteria:

IBD patients in remission, SCCAI ≤ 2 (Simple Clinical Colitis Activity Index )) or HBI \< 5 (Harvey \& Bradshaw Activity Index ) or in mild to moderate disease activity ( SCCAI 3-4, HBI \< 16) IBD patients who can read, speak and understand Danish. IBD patients that can take advantage of the Internet and wireless network. 18 years or older.

Exclusion criteria:

IBD patients with severe disease activity HB \> 16 SCCAI ≥ 5 IBD patients with social, medical or psychological issues of a more complex character. IBD patients with particularly complex issues such as drug and alcohol problems, severe mental / psychiatric disorders and / or serious social impact.IBD patients who cannot attend due language barrier or cognitive disorder. Age less than 18.

When the patient has agreed to participate in the study, randomized to either OD or 3. Months (This has been done ClinicalTrials.gov ID: NCT02492555)

Patients log in to www.noh.constant-care.dk at least once every 3rd months throughout the project period of 11 years in total (2015-2026). When the patient log in to the telemedicine platform the following scorings must be filled out:

1. - Disease activity (DA), respectively SCCAI or HBI.
2. - Quality of life assessment, s-IBDQ
3. - FACIT (Fatigue score)
4. - MARS ( Medical Adherence Rating Scale)
5. - FC, fecal calprotectin mg / kg measured by the patient's own SMART phone, rapid home test.

If the patients prefer to send the fecal samples for test, it will be analyzed in the ehealth gastro lab. at the hospital with a SMART phone as well.

The results of the scoring systems will appear to the health care professionals and patients in a traffic light manner (red, yellow and green).

If the patient experiences a recurrence of the disease, it moves from green to either yellow or red area in the traffic graph, and patient will further be instructed to contact Gastro medical clinic project nurse for an early consultation and decision on further treatment initiative. This will also be indicated at the patient's website. If alarm symptoms occurs patients are instructed to contact the project nurse. Thus patients are treated in accordance to national and international guideline. By screening of the inflammation burden (web algorithm), the decision is moving forward.

Patients logging in on demand, indicate disease activity, quality of life and FC at the start, and subsequently when needed and at the end of the study (after 11 years from inclusion).

At relapse, disease activity score and FC is settled and repeated no later than 7 days here after. When the patient has reached remission (green) a new DA and FC test should be performed to verify the remission.

The purpose of this study is to determine if the IBD patients doing home monitoring have relative reduced rates of colectomies, resections, mortalities and cancer after 11 years of web monitoring. Relative reduced rates of colectomies etc. means - relative to standard care but also if there is a difference between the two web screening procedures on these endpoints.

120 IBD patients has been randomized to screen for disease activity and FC either OD or every 3 months. 60 patients in each group

Are Rates of Colectomies, Resections, Mortalities and Cancer Reduced by Home Monitoring of IBD Patients ?

Are Rates of Colectomies, Resections, Mortalities and Cancer Reduced by Home Monitoring of IBD Patients Tightly on Demand or Every 3 Months by Fecal Calprotectin and Disease Activity?

Both AUC total, but also as a red \>600 mg/kg, yellow (200-600 mg/kg) and green (below 200mg/kg ) AUC will be performed from the individualized curves

Both AUC total, but also as a red \>5, yellow (2-4) and green (\< 2 ) AUC will be performed from the individualized curves

Both AUC total, but also as a red \>16 , yellow (6-16) and green (≤5) AUC will be performed from the individualized curves

Based on epidemiology four figures have been developed to describe disease-course of IBD. These figures have been used in a retrospective study (Maagaard et al. 2016) to measure change in Disease course.The four figures depicting different types of disease courses is described as follows:

1. Mild IBD with indolent course
2. Mild IBD with aggressive course
3. Chronic IBD with continuous course
4. Chronic IBD with intermittent course The patients have to choose one figure representing their disease course type the best at inclusion and 11 years later

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Cytokines in Blister Fluids of Bullous Pemphigoid (BP)	NCT03856840	Pemphigoid, Bul...		18 Years -	Istanbul Medeniyet University
Cytokines in Blister Fluids of Bullous Pemphigoid (BP)	NCT03856840	Pemphigoid, Bul...		18 Years -	Istanbul Medeniyet University
Cytokines in Blister Fluids of Bullous Pemphigoid (BP)	NCT03856840	Pemphigoid, Bul...		18 Years -	Istanbul Medeniyet University
Are Rates of Colectomies, Resections, Mortalities and Cancer Reduced by Home Monitoring of IBD Patients ?	NCT03038984	Inflammatory Bo...	At Home Screeni... At Home Screeni...	18 Years -	Nordsjaellands Hospital

Spots Global Cancer Trial Database for disease activity