Adalimumab in the Treatment of Chronic Pouchitis

Study Overview
=================
Brief Summary
-----------------
This study wants to investigate the efficiency of biological treatment for chronic pouchitis. Chronic pouchitis is inflammation in a reconstruction after removal of the colon, a pouch. It is examined in patients with ulcerative colitis. The primary objective evaluation is to evaluate the clinically effect of biological therapy (adalimumab) in patients with chronic pouchitis. Secondary objective is to evaluate the effect of biological therapy on the endoscopical and histological inflammatory activity. It is a double-blinded randomized placebo controlled study.

Official Title
-----------------
Adalimumab (Humira) in the Treatment of Chronic Pouchitis

Conditions
-----------------
Ulcerative Colitis, Pouchitis

Intervention / Treatment
-----------------
* Drug: Adalimumab
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Operated with proctocolectomy and construction of an IPAA Prior to surgery diagnosed with ulcerative colitis according to established clinically, radiologic, endoscopic and histological criteria. Diagnosed with chronic pouchitis as defined above PDAI ≥ 7, with the clinically part of PDAI >2 and the endoscopic part of PDAI >3 Age >18 years Negative stool cultures for bacterial bowel pathogens and negative stool microscopy for parasites Serology negative for chronic hepatitis B Negative examination for tuberculosis (including x-ray of thorax and a interferon gamma test) Signed informed consent Exclusion Criteria: Treatment with glucocorticoids within the last 4 weeks Diagnosed with Crohn's disease Need of an interpreter or if patients do not understand oral or written information. Surgical complications as anal stenosis, leak of the anastomosis, or fistula arising from the pouch Abuse of medicine, alcohol or drugs Ongoing treatment with NSAID (non steroid anti inflammatory drug) Pregnancy or nursing A diverting stoma Malignancy or other severe chronic disease or expected longevity less than one year Patients diagnosed with immune deficiency Ongoing infectious disease Contraindications against treatment with tumor necrosis factor-alpha antibody, such as heart disease, former cancer disease, in vivo vaccination within the last 4 weeks

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Adalimumab<br>Every second week, mg: 160-80-40-40-40-40 12 weeks in all | Drug: Adalimumab<br> <br> * Other names: Humira;|
| Placebo Comparator: Placebo<br>Given as the active comparator, every second week | Drug: Placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response on treatment with Adalimumab | The number of patients with chronic pouchitis achieving a clinical improvement, defined as a reduction in clinically PDAI ≥ 2 at any time within the 12 weeks of treatment with adalimumab (Humira). Clinical PDAI (0-6 points)(pouchitis disease activity index)refers to fewer (0-1 point), number of bowel movements(0-2 points), rectal bleeding(0-1 point) and fecal urgency(0-2 points). | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical improvement after 12 weeks of treatment | The number of patients with a clinical improvement (PDAI reduction ≥ 2)at week 12 See the description of clinical improvement and PDAI under primary endpoint | 12 weeks | 
| Clinical remission after 12 weeks | The number of patients with pouchitis in remission at week 12 (total PDAI ≤4) | 12 weeks | 
| Endoscopic and histologic response after treatment with Adalimumab | Effect (reduction in PDAI)of adalimumab (Humira) on the endoscopical and histological activity in chronic pouchitis Endoscopical and histological activity is defined from PDAI (pouchitis disease activity index). Endoscopically the presence of Edema, Granularity, Friability, Loss of vascular pattern, Mucous exudates or Ulceration, gives 1 point each (max 6 points). Histological the presence of polymorphic nuclear leukocyte infiltration and ulceration each gives 1-3 points regarding severity (max 6 points) | 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
IPAA, Pouchitis, Ulcerative colitis, Pouch, Adalimumab, Humira