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| Sponsor: | National Institute of Allergy and Infectious Diseases (NIAID) |
|---|---|
| Information provided by: | National Institute of Allergy and Infectious Diseases (NIAID) |
| ClinicalTrials.gov Identifier: | NCT00128193 |
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Leprosy |
Drug: MLSA-LAM Drug: MLCwA Drug: Placebo Drug: RT-23 Drug: Tuberculin, Purified Protein Derivative (Tubersol®) |
Phase II |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Diagnostic |
| Official Title: | Two New Leprosy Skin Test Antigens: MLSA-LAM and MLCwA Phase II Study in a Leprosy-Endemic Region |
| Enrollment: | 260 |
| Study Start Date: | April 2002 |
| Study Completion Date: | October 2009 |
| Primary Completion Date: | October 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: A1-Ramping (MLSA-LAM)
5 subjects to receive: 1.0 mcg of MLSA-LAM, 0.1 mcg of MLSA-LAM, 5 TU Purified Protein Derivative/Tubersol®, saline (NaCl).
|
Drug: MLSA-LAM
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).
Drug: Placebo
Saline (NaCl) serves as a diluent control in Stage A and B only.
Drug: Tuberculin, Purified Protein Derivative (Tubersol®)
Licensed TB reagent, 100 microliters, 5 TU dose.
|
|
Experimental: A2-Ramping (MLCwA)
5 subjects to receive: 1.0 mcg of MLCwA, 0.1 mcg of MLCwA, 5 TU Purified Protein Derivative/Tubersol®, saline (NaCl).
|
Drug: MLCwA
Cell wall-associated proteins of Mycobacterium leprae; dosages 0.1 and 1.0 micrograms; administered in sterile diluent 0.9% saline (NaCl).
Drug: Placebo
Saline (NaCl) serves as a diluent control in Stage A and B only.
Drug: Tuberculin, Purified Protein Derivative (Tubersol®)
Licensed TB reagent, 100 microliters, 5 TU dose.
|
|
Experimental: B2-Full-Scale (MLCwA)
45 subjects to receive: 1.0 mcg of MLCwA, 0.1 mcg of MLCwA, 5 TU Purified Protein Derivative/Tubersol®, saline (NaCl).
|
Drug: MLCwA
Cell wall-associated proteins of Mycobacterium leprae; dosages 0.1 and 1.0 micrograms; administered in sterile diluent 0.9% saline (NaCl).
Drug: Placebo
Saline (NaCl) serves as a diluent control in Stage A and B only.
Drug: Tuberculin, Purified Protein Derivative (Tubersol®)
Licensed TB reagent, 100 microliters, 5 TU dose.
|
|
Experimental: B1-Full-Scale (MLSA-LAM)
45 subjects to receive: 1.0 mcg of MLSA-LAM, 0.1 mcg of MLSA-LAM, 5 TU Purified Protein Derivative/Tubersol®, saline (NaCl).
|
Drug: MLSA-LAM
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).
Drug: Placebo
Saline (NaCl) serves as a diluent control in Stage A and B only.
Drug: Tuberculin, Purified Protein Derivative (Tubersol®)
Licensed TB reagent, 100 microliters, 5 TU dose.
|
|
Experimental: C-1b-Target Population (Low Dose)
80 subjects to receive: 0.1 mcg MLSA-LAM, 0.1 mcg MLCwA, 2 TU Purified Protein Derivative/RT-23.
|
Drug: MLSA-LAM
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).
Drug: MLCwA
Cell wall-associated proteins of Mycobacterium leprae; dosages 0.1 and 1.0 micrograms; administered in sterile diluent 0.9% saline (NaCl).
Drug: RT-23
2 TU dose.
|
|
Experimental: C1-Target Population
80 subjects to receive: 1.0 mcg of MLSA-LAM, 1.0 mcg of MLCwA and 2TU Purified Protein Derivative/RT-23.
|
Drug: MLSA-LAM
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).
Drug: MLCwA
Cell wall-associated proteins of Mycobacterium leprae; dosages 0.1 and 1.0 micrograms; administered in sterile diluent 0.9% saline (NaCl).
Drug: RT-23
2 TU dose.
|
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 antigen, Phenolic Glycolipid - I (PGL-I) are present in serum from leprosy patients, leprosy patient contacts, TB patients, and healthy non-exposed subjects, using a lateral flow immunodiffusion rapid test kit. Results will be compared to the magnitude of skin test response.
Eligibility| Ages Eligible for Study: | 18 Years to 60 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
All Subjects
Healthy, Non-Contacts
Contacts of Leprosy Patients
Persons with Leprosy
Having one or more of the following symptoms:
Persons with Tuberculosis
Having active tuberculosis as defined by one of the following:
Exclusion Criteria:
All subjects
Healthy, Non-Contacts
Healthy Contacts of Leprosy Patients
Persons with Leprosy
Persons with Tuberculosis
Contacts and Locations| United States, Colorado | |
| Colorado State University | |
| Fort Collins, Colorado, United States, 80523 | |
| Nepal | |
| Anandaban Hospital | |
| Kathmandu, Nepal | |
| Lalitpur Nursing Campus | |
| Kathmandu, Nepal | |
| Green Pastures Hospitals | |
| Kathmandu, Nepal | |
| Lal Gadh Hospital | |
| Kathmandu, Nepal | |
| Patan Hospital | |
| Kathmandu, Nepal | |
| Tribhuvan University | |
| Kathmandu, Nepal | |
More Information
| Responsible Party: | Director ORA, HHS/NIAID/DMID |
| ClinicalTrials.gov Identifier: | NCT00128193 History of Changes |
| Other Study ID Numbers: | 00-002 |
| Study First Received: | August 5, 2005 |
| Results First Received: | September 30, 2010 |
| Last Updated: | November 3, 2011 |
| Health Authority: | Nepal: Health Research Council; United States: Federal Government; United States: Food and Drug Administration; United States: Institutional Review Board |
|
leprosy, Mycobacterium leprae, Hansen's Disease, skin test, Nepal |
|
Leprosy Mycobacterium Infections Actinomycetales Infections Gram-Positive Bacterial Infections Bacterial Infections |