Leprosy Skin Test Antigens Trial
Condition: Leprosy
MeSH terms: Leprosy
Study type: Interventional
Phase: Phase 2

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.
    

Detailed 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
    

Intervention name(s): Tuberculin, Purified Protein Derivative; MLSA-LAM; MLCwA; Tuberculin, Purified Protein Derivative; Placebo
Intervention type(s): Biological; Other; Other; Biological; Other
Intervention description(s): A tuberculin skin test used to diagnose latent tuberculosis (TB) infection. 2 TU dose; Mycobacterium leprae soluble antigen with minimal amounts of immunosuppressive lipoglycans; dosages 0.1 and 1.0 micrograms; administered in sterile diluent 0.9% saline (NaCl).; Cell wall-associated proteins of Mycobacterium leprae; dosages 0.1 and 1.0 micrograms; administered in sterile diluent 0.9% saline (NaCl).; Licensed TB reagent, 100 microliters, 5 TU dose.; Saline (NaCl) serves as a diluent control in Stage A and B only.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Diagnostic
Keywords: leprosy, Mycobacterium leprae, Hansen's Disease, skin test, Nepal