Leprosy Skin Test Antigens Trial

Leprosy Clinical Trial

Official title: Two New Leprosy Skin Test Antigens: MLSA-LAM and MLCwA Phase II Study in a Leprosy-Endemic Region

Status Completed

Clinical Trial Summary

The purpose of this study is to see how healthy people and leprosy patients react to 2 new skin tests for detecting leprosy. The study will evaluate the new skin tests that may aid in measuring the number of people exposed to leprosy and enable its diagnosis and treatment at an earlier stage. Participant's ages 18-60 living in Kathmandu, Nepal will be enrolled. Stages A and B of the study will use the skin test in healthy volunteers. Stage C will use the skin test in high risk volunteers (including individuals with leprosy), healthy individuals in contact with leprosy patients and individuals with tuberculosis (TB, lung disease). Study procedures will include injections, physical exam, and blood testing. Injection sites will be checked several times during the participant's study involvement (5 hours of time spread over approximately 1 month). Volunteers screened for the study, which have leprosy or tuberculosis will be treated or referred for treatment.

Clinical Trial Description

This double-blind Phase II clinical trial will be conducted in 3 stages to evaluate 2 new leprosy skin test antigens, Mycobacterium (M.) leprae Soluble Antigen (MLSA)-Lipoarabinomannan (LAM) and M. leprae Cell Wall Antigen (MLCwA), as diagnostic-epidemiological tools designed to measure incidence of leprosy infection in Kathmandu, Nepal, a leprosy endemic area. Stage A will provide an initial indication of safety of the 2 new test antigens in 10 healthy members of the leprosy endemic population (5 subjects per antigen at 2 dosages each). Stage B will expand this analysis by an additional 90 healthy subjects (45 subjects per antigen). If any subjects in Stage A or B show ulcerations at the 1.0 mcg dose of MLSA-LAM or MLCwA test sites, then only the 0.1 mcg dose will be used for Stage C. The final stage, Stage C, is divided into 2 parts. The first part, Stage C-1, will assess safety of both antigens at the high dose (1.0 mcg) in populations at a higher risk of developing ulcerations at skin test sites. Eighty subjects will be recruited: 20 household contacts of Borderline Lepromatous Leprosy (BL) / Lepromatous Leprosy (LL) leprosy patients, 20 BL/LL leprosy patients, 20 Borderline Tuberculoid Leprosy (BT) / Tuberculoid Leprosy (TT) patients and 20 tuberculosis (TB) patients. The second part, Stage C-1b, is a continuation of Stage C-1 with the same number of subjects recruited from the same groups to assess the reactivity of both antigens at the low dose (0.1 mcg). This study will define a positive skin test reaction for MLSA-LAM and MLCwA, and this definition will be used in estimating sensitivity and specificity for each skin test antigen and dosage. It is expected that the BT/TT leprosy patients and healthy contacts of leprosy patients will have larger indurations at both M. leprae-derived antigen sites and a variable reaction at the tuberculin/Purified Protein Derivative (PPD) site. The non-contacts, BL/LL leprosy patients, and TB patients will have smaller indurations at all leprosy skin test sites and a variable reaction at the tuberculin/PPD site. Finally, the TB patients will react with a large induration at the tuberculin/PPD site. Primary study objectives are to evaluate safety of these 2 new leprosy skin test antigens and to estimate specificity and sensitivity of these skin test antigens in detecting M. leprae infection by: selecting a dosage of the MLSA-LAM and MLCwA antigens that causes minimal induration in healthy non-exposed subjects; selecting a size of induration that will serve as a definition of a positive skin test reaction for MLSA-LAM and MLCwA in leprosy patients; and comparing proportion of positive skin test reactors in healthy subjects to proportion in BT/TT and BL/LL leprosy patients, contacts of leprosy patients, and TB patients. Secondary study objectives are to compare mean size of induration in response to each test antigen in healthy subjects versus BT/TT and BL/LL leprosy patients, contacts of leprosy patients, and TB patients as a measure of specificity and sensitivity; to compare the specificity and sensitivity of the 2 new antigens with tuberculin/PPD in patients with clinical leprosy, contacts of leprosy patients, and healthy unexposed subjects (non-patient contacts); to quantify release of IFN-gamma from lymphocytes in whole blood from leprosy patients, leprosy patient contacts, TB patients, and healthy nonexposed subjects, following in vitro stimulation with leprosy skin test antigens and PPD, using the QuantiFERON-CMI (Cellestis Limited, Valentia California) kit. Results will be compared to the magnitude of the skin test response; and to determine if antibodies against a M. leprae specific anti ;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Leprosy

• NCT number: NCT00128193
• Study type: Interventional
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Status: Completed
• Phase: Phase 2
• Start date: April 2002
• Completion date: September 2009