Intestinal Inflammation in Ankylosing Spondylitis and the Effects of Adalimumab on Mucosal Healing

NCT01174186 | Completed Phase 4 Results DMC

• 1 other identifier: 4682724
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 4

Brief Summary

Studies with intestinally asymptomatic patients with spondyloarthritis showed that approximately 1/3 had visible ulcers in the colon by scopic examinations and 2/3 had changes detectable by microscopy. Only those patients who improved in arthritis symptoms showed improvement in colonic changes. In these studies only colon and the terminal ileum was examined. Inflammation of the small intestine was not examined. Newer studies have shown an immunological link between Crohns disease and spondyloarthritis but not ulcerative colitis. The investigators wish to examine the small intestine in these patients before and after treatment, since they expect to find ulcers there linking spondyloarthritis to Crohns disease and healing after treatment.

Conditions

Spondyloarthritis; Enterocolitis

Outcome Measures

Primary Outcomes (2)

• Change Lewis Score Index

  Lewis' score describes the amount of inflammation seen optically by capsular endoscopy. Gralnek et al. devised and validated the Lewis score index, based on three endoscopic parameters: villous edema, ulcer and stenosis/stricture. Using these parameters, the authors established a score range of 8-4,800 points where: LS \< 135 reflects normal mucosal appearances, LS 135-790 mild mucosal inflammatory change and an LS value ≥790 moderate to severe mucosal inflammatory changes. The patients had endoscopy performed at baseline and again after 20 weeks. The number of patients improving was compared to number of patients deteriorating

  20 weeks

• Change in Intestinal Inflammation Measured by Faecal Calprotectin

  Feacal calprotectin is a protein and a marker of the degree of inflammation in the intestine, but not the site of inflammation. We measured the level calprotectin continuously in each of the patients. Difference was inferred by repeated measurement ANOVA

  Baseline to 52 weeks

Secondary Outcomes (2)

• Spondyloarthritis Consortium of Canada Score

  one year

• Assessment Group in Ankylosing Spondylitis (ASAS) Core Set for Clinical Practice

  one year

Study Arms (2)

Spondyloarthritis and calprotectin elevated

ACTIVE COMPARATOR

Spondylitis patients with elevated levels of fecal calprotectin. Patients are treated with adalimumab

Drug: Adalimumab

Spondyloarthritis and calprotectin normal

ACTIVE COMPARATOR

Spondylitis patients with normal levels of fecal calprotectin. Patients are treated with adalimumab.

Drug: Adalimumab

Interventions

Adalimumab DRUG

Tumor Necrosis Factor (TNF) alpha inhibitor given 40 mg subcutaneously every other week except the first time where 80 mg is given

Also known as: Humira

Spondyloarthritis and calprotectin elevated; Spondyloarthritis and calprotectin normal

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients (18 years and ≤45 years) with axial SpA according to the ASAS criteria
• Active SpA assessed by physician.
• Bath Ankylosing Spondylitis Disease Activity Index (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.

You may not qualify if:

• Diagnosed inflammatory bowel disease or high risk of intestinal stricture (previous abdominal stricture, radiation of abdomen, major abdominal surgery).
• Psoriasis
• Persons with latent Tuberculosis (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.
• 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. optic 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), 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 clinically significant inflammatory rheumatologic diseases that cannot be related to spondyloarthritis
• Current parvovirus B 19 infection.

Sponsors & Collaborators

• Regionshospitalet Silkeborg: lead
• Abbott: collaborator
• Medtronic - MITG: collaborator
• Central Denmark Region: collaborator

Study Sites (4)

Department of Rheumatology U, Aarhus Hospital

Aarhus, 8000, Denmark

Location

Regional Hospital of Horsens, Department of Medicine

Horsens, 8700, Denmark

Location

Regional Hospital of Randers, Department of Medicine

Randers, Denmark

Location

Regional Hospital of Silkeborg

Silkeborg, 8600, Denmark

Location

MeSH Terms

Conditions

Spondylarthritis; Enterocolitis

Interventions

Adalimumab

Condition Hierarchy (Ancestors)

Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Arthritis; Joint Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

15 participants in each group is not many, but the number was selected based on an a priori analysis. NSAID wash-out period of 4 weeks was chosen as best estimate. Loading dose of adalimumab was given to calprotectin elevated group

Results Point of Contact

• Title: René Oestgaard
• Organization: Silkeborg Regional Hospital

ostgard@immunology.au.dk

0045 78 41 50 00

Study Officials

• Henning Glerup, M.D.

  Regional Hospital Silkeborg, medical department

  STUDY CHAIR

• René D Oestgaard, M.D.

  Regional Hospital Silkeborg, medical department

  STUDY DIRECTOR

• Bent Deleuran, M.D.

  Department of Medical Microbiology and Immunology Aarhus University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: René Østgård, MD, Regional Hospital Denmark, medical department

Study Record Dates

• First Submitted: July 16, 2010
• First Posted: August 3, 2010
• Study Start: October 1, 2010
• Primary Completion: June 1, 2013
• Study Completion: March 1, 2014
• Last Updated: December 2, 2014
• Results First Posted: November 17, 2014

Record last verified: 2014-11

Locations

DK (4)