Intestinal Tuberculosis Diagnostics and the Differentiation From Crohn's Disease

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

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.

Study Overview

• Status: Unknown
• Conditions: Crohn's Disease; Pulmonary Tuberculosis; Intestinal Tuberculosis

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 Type: Observational
• Enrollment (Anticipated): 550

Contacts and Locations

Study Locations

• India
  • Kerala
    • Trivandrum, Kerala, India, 695011
      • Recruiting
      • Population Health & Research Institiute, Medical College
      • Contact: KT Shenoy, M.D. Ph.D; Phone Number: +91 9447044364; Email: dr.ktshenoy@gmail.com
      • Principal Investigator: KT Shenoy, M.D Ph.D
      • Sub-Investigator: Geir Larsson, M.D
• Norway
  • Oslo, Norway, 0440
    • Active, not recruiting
    • Lovisenberg Diakonal Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Consecutive patients from four secondary or tertiary care referral centres in the two southernmost states in India (Kerala and Tamil Nadu).

Consecutive patients from nine secondary or tertiary care referral centres in South-East Norway.

Description

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):

  1. Endoscopic apparent intestinal tuberculosis: transverse ulcers, pseudopolyps, involvement of fewer than four intestinal segments, patulous ileo-coecal valve
  2. Histological evidence of tubercles/granulomas with caseation necrosis in intestinal biopsies
  3. DNA of M.tb detected by PCR of intestinal biopsies
  4. Positive immunohistochemistry in intestinal biopsies.
  5. 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:

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

Exclusion Criteria:

a) Age below 18 years b) HIV positive c) Malignancy

Study Plan

How is the study designed?

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Calprotectin levels in patients with active intestinal tuberculosis	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.	18 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Levels of calprotectin in patients with intestinal tuberculosis after antituberculous therapy.	18 months

Collaborators and Investigators

• Sponsor: Lovisenberg Diakonale Hospital
• Collaborators: 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

Publications and helpful links

General Publications

• Larsson, G; Shenoy, KT; Roseth, A; Bjune, G; Moum, B. Diagnosis and differentiation of intestinal tuberculosis and Crohn's disease by use of faecal and serum calprotectin. INFLAMMATORY BOWEL DISEASES 17: S35-S35 Suppl. 1 JAN 2011

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (ANTICIPATED): December 1, 2011
• Study Completion (ANTICIPATED): December 1, 2012

Study Registration Dates

• First Submitted: December 30, 2011
• First Submitted That Met QC Criteria: December 30, 2011
• First Posted (ESTIMATE): January 2, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): January 2, 2012
• Last Update Submitted That Met QC Criteria: December 30, 2011
• Last Verified: December 1, 2011

More Information

Terms related to this study

• Keywords: CD; ITB; PTB
• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Inflammatory Bowel Diseases; Tuberculosis; Crohn Disease; Tuberculosis, Pulmonary
• Other Study ID Numbers: LDS 150