Intestinal inflammation in ankylosing spondylitis assessed by stoll samples and endoscopy and the effects of adalimumab on inflammation

• Register: EUCTR
• Last refreshed on: 3 October 2016
• Main ID: EUCTR2009-018085-35-DK
• Date of registration: 05/05/2010
• Prospective Registration: Yes
• Primary sponsor: Regionalhospital Silkeborg
• Public title: Intestinal inflammation in ankylosing spondylitis assessed by stoll samples and endoscopy and the effects of adalimumab on inflammation
• Scientific title: Intestinal Inflammation in Ankylosing Spondylitis assessed by Fecal Calprotectin, Capsular Endoscopy and Colonoscopy and the effects of Adalimumab on mucosal healing - INTASAH
• Date of first enrolment: 21/05/2010
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-018085-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Denmark

Contacts

• Name: Studieledelse
• Affiliation: Regionshospitalet Silkeborg

• Name: Studieledelse
• Affiliation: Regionshospitalet Silkeborg

Key inclusion & exclusion criteria

Inclusion criteria:
Patients (>18 years and =45 years) with axial SpA according to the ASAS criteria
Active SpA assessed by physician.
BASDAI = 4.
Faecal calprotectin = 100mg/kg.
Negative pregnancy test (serum-HCG) for women of childbearing age before the start of the study. (Women not of childbearing age are defined as postmenopausal for at least 1 year or surgically sterilised (bilateral tubal ligation, bilateral oophorectomy or hysterectomy)). Women of childbearing age included in the study will be required to use contraception during the entire study period (i.e. one of the following: contraceptive pills, intrauterine device, depot injection of gestagen, subdermal implant, hormonal vaginal ring or transdermal patch). In addition, contraception must be used following any discontinuation of the study drug for a period of 150 days.
Ability and willingness to self-administer the subcutaneous injections or have a person available to administer the injections.
Ability and willingness to give written informed consent and meet the requirements of the study protocol.
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 40
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Diagnosed inflammatory bowel disease or high risk of intestinal stricture (previous abdominal stricture, radiation of abdomen, major abdominal surgery).
NSAID ingestion less than 4 weeks before inclusion.
Persons with latent TB (positive Mantoux skin test (>10 mm), positive cultivation for mycobacteria in tissue samples and/or chest X-ray indicating TB) or other risk factors for activation of untreated latent TB.
Current or recurrent infections or serious infections requiring hospitalisation or treatment with intravenous antibiotics within the last 30 days or oral antibiotics within the last 14 days before inclusion.
Positive serology for Hepatitis B or C indicating active infection.
Medical history of positive HIV status (in case of suspicion control of HIV test).
Medical history of histoplasmosis or listeriosis.
Previous cancer or lymphoid proliferative disease except completely well-treated cutaneous squamous cell carcinoma, basal cell carcinoma or cervical dysplasia.
Previous diagnosis or signs of demyelinising diseases of the central nervous system (e.g. opticus neuritis, disturbance of vision, disturbed gait/ataxia, facial paresis, apraxia).Severe renal insufficiency (creatinine clearance < 35 ml/min - normogram).
Affected hepatic function: Liver enzymes > 3 x above the normal limit.
Clinically significant drug or alcohol abuse in the last year or daily current alcohol consumption.
Diabetes, unstable ischemic heart disease, heart failure (NYHA III-IV), active chronic inflammatory bowel disease, recent apoplexia cerebri (within 3 months), chronic leg ulcer and any other condition (e.g. indwelling catheter) which at the discretion of the investigator means that participation in the protocol would entail a risk for the person in question.
Anticoagulant treatment.
Pregnancy or breast-feeding.
Other inflammatory rheumatologic diseases that cannot be related to spondyloarthritis
Current parvovirus B 19 infection.
Glucocorticosteroid treatment within the last 4 weeks (except nasal and inhalation steroids). Contraindication to study drug.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Ankylosing spondylitis Inflammatory bowel disease
MedDRA version: 14.0 Level: PT Classification code 10061371 Term: Spondylitis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
MedDRA version: 14.0 Level: LLT Classification code 10041672 Term: Spondylitis ankylosing System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
MedDRA version: 14.0 Level: LLT Classification code 10048398 Term: Spondylitis ankylosing aggravated System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
MedDRA version: 14.0 Level: LLT Classification code 10041671 Term: Spondylitis ankylopoietica System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
MedDRA version: 14.0 Level: PT Classification code 10002556 Term: Ankylosing spondylitis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
MedDRA version: 14.0 Level: LLT Classification code 10041673 Term: Spondylitis NOS System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Trade Name: Humira
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ADALIMUMAB
CAS Number: 331731-18-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-

Primary Outcome(s)

Main Objective: To establish the proportion of otherwise intestinally low-symptomatic patients with intestinal ulcers in patients diagnosed with active spondyloarthritis and to illustrate the healing rate following treatment with the TNF-alpha inhibitor adalimumab

Primary end point(s): 1: Mucosal healing after 20 weeks of treatment with adalimumab assessed using Lewis scoring following capsular endoscopy. (Null hypothesis: Treatment for 20 weeks with adalimumab results in no variation in patients with Lewis scoring under 135 following.)
2: Description whether intestinal ulcers occur in the small bowel in patients with spondyloarthritis assessed by measurement of faecal calprotectin during 52 weeks of treatment (Null hypothesis: No intestinal changes occur in patients with spondyloarthritis)

Secondary Objective: The proportion of patients (%) with mucosal healing of ileal and colon lesions following treatment with adalimumab. • The change in disease activity assessed using ASAS core set for daily practice (25) and BASDAI, BASMI as well as BASFI before and after treatment with adalimumab. • The change in MRI scanning score before and after treatment with adalimumab.
The correlation between change in Lewis score and change in faecal calprotectin.
The correlation between change in disease activity in AS and change in Lewis score.
The correlation between change in AS disease activity assessed by cellular and soluble inflammation markers and change in intestinal inflammation.
The correlation between change in AS activity assessed using MRI of sacroiliac joint and the whole spine and change in intestinal inflammation.
The correlation between change in AS activity assessed using MRI of sacroiliac joint and the whole spine and change in cellular and soluble inflammation markers.

Timepoint(s) of evaluation of this end point: 1: 20 weeks
2: 52 weeks

Secondary Outcome(s)

Secondary end point(s): • The proportion of patients (%) with mucosal healing of ileal and colon lesions following treatment with adalimumab.
• The change in disease activity assessed using ASAS core set for daily practice (25) and BASDAI, BASMI as well as BASFI before and after treatment with adalimumab.
• The change in MRI scanning score before and after treatment with adalimumab.
• The correlation between change in Lewis score and change in faecal calprotectin.
• The correlation between change in disease activity in AS and change in Lewis score.
• The correlation between change in AS disease activity assessed by cellular and soluble inflammation markers and change in intestinal inflammation.
• The correlation between change in AS activity assessed using MRI of sacroiliac joint and the whole spine and change in intestinal inflammation.
• The correlation between change in AS activity assessed using MRI of sacroiliac joint and the whole spine and change in cellular and soluble inflammation markers.

Timepoint(s) of evaluation of this end point: 20 and 52 weeks of treatment

Secondary ID(s)

NCT01174186

4682724

Source(s) of Monetary Support

Gigtforeningen

Abbott Laboratories

European Capusule Endoscopy Group

Region Midtjylland

Regionshospitalet Silkeborg