Intestinal Tuberculosis Diagnostics and the Differentiation From Crohn's Disease

Sponsor

Lovisenberg Diakonale Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT01503099

Collaborator

Helse Sor-Ost (Other), The Unger-Vetlesen Medical Fund, Jersey, C.I (Other), Odd Fellow Medical Fund, Norway (Other)

550

Enrollment

Locations

Duration (Months)

275

Patients Per Site

7.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

One aims to devise a method for the screening and differentiation of intestinal tuberculosis and Crohn's Disease. Additionally, one aims to detect and survey multidrug resistant TB.

Condition or Disease	Intervention/Treatment	Phase
Intestinal Tuberculosis Pulmonary Tuberculosis Crohn's Disease

Detailed Description

Intestinal tuberculosis (ITB) and Crohn's disease (CD) may present identically; the consequence of misdiagnosing and mistreating one disease for the other may be grave. CD is on the increase worldwide while TB re-emerges in areas of low TB endemicity. Current diagnostic guidelines evolve from research in areas with low TB prevalence, thereby being inappropriate in TB endemic regions. To date, no simple or non-invasive methods exist to diagnose ITB and to differentiate it from CD.

One aims to devise a method for screening and differentiation of the two diseases. By using non-invasive rapid tests one wishes to make diagnostics available to resource poor settings. Ideally, referrals to invasive diagnostic procedures would decrease, thus liberating economic and staff resources. Furthermore, patients may avoid unnecessary, expensive and often inconclusive advanced procedures. Additionally, one aims to detect and survey multidrug resistance caused by empiric TB treatment, which in itself obscures ITB diagnosis.

This case control study matches 50 ITB patients and 50 CD patients with 100 healthy controls in India, and 50 CD patients with 100 healthy controls in Norway. Comparative statistical analysis will be carried out. Challenges include patient adherence and sample handling. Non-TB gastrointestinal infections may confound the results and will be adjusted for.

Recently published data suggests that the serum/faecal calprotectin ratio may be used to discriminate ITB from healthy subjects.

Study Design

Study Type:

Observational

Anticipated Enrollment :

550 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Intestinal Tuberculosis Diagnostics and the Differentiation From Crohn's Disease in Populations of High vs. Low Tuberculosis Endemicity

Study Start Date :

Oct 1, 2009

Anticipated Primary Completion Date :

Dec 1, 2011

Anticipated Study Completion Date :

Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active ITB Patients with active intestinal tuberculosis (ITB)
Controls India Healthy subjects serving as controls
CD India Patients with active Crohn's Disease (CD) in India
Active PTB Patients with active pulmonary tuberculosis (PTB)
CD Norway Patients with active Crohn's Disease (CD) in Norway
Controls Norway Healthy subjects serving as controls in Norway

Outcome Measures

Primary Outcome Measures

Calprotectin levels in patients with active intestinal tuberculosis [18 months]
Establishment of serum and faecal calprotectin levels in patients with active intestinal tuberculosis in comparison with healthy control subjects, patients with Crohn's Disease and patients with active pulmonary tuberculosis.

Secondary Outcome Measures

Levels of calprotectin in patients with intestinal tuberculosis after antituberculous therapy. [18 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Above 18 years of age.
ITB as per standard criteria a), and one or more of b) to e) must be fulfilled (Gold standard):

Endoscopic apparent intestinal tuberculosis: transverse ulcers, pseudopolyps, involvement of fewer than four intestinal segments, patulous ileo-coecal valve
Histological evidence of tubercles/granulomas with caseation necrosis in intestinal biopsies
DNA of M.tb detected by PCR of intestinal biopsies
Positive immunohistochemistry in intestinal biopsies.
Histological demonstration of acid fast bacilli in a lesion.

Active Crohn's disease as per standard criteria (Gold standard), at least two of the following:

Clinical: inflammatory, perforating (fistulising) disease, obstructive symptoms secondary to small bowel stenosis or stricture.
Endoscopic: deep linear or serpingenous ulcerations, discrete ulcers in normal appearing mucosa, cobble-stoning or discontinuous or asymmetrical inflammation.
Radiographic: segmental disease (skip lesions), small bowel or colonic strictures, stenosis or fistula.
Histological: sub-mucosal or transmural inflammation, granulomas, focal cryptitis and chronic inflammatory infiltration, skip lesions including rectal sparing (no topical rectal therapy).

Exclusion Criteria:

Age below 18 years b) HIV positive c) Malignancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Population Health & Research Institiute, Medical College	Trivandrum	Kerala	India	695011
2	Lovisenberg Diakonal Hospital	Oslo		Norway	0440

Sponsors and Collaborators

Lovisenberg Diakonale Hospital
Helse Sor-Ost
The Unger-Vetlesen Medical Fund, Jersey, C.I
Odd Fellow Medical Fund, Norway

Investigators

Study Chair: Bjorn Moum, M.D Ph.D, Oslo University Hospital, Aker
Study Chair: Gunnar Bjune, M.D Ph.D, University of Oslo, Dept. of International Health