Molecular and Immunological Tools for Detection of Strain Diversity, Drug Resistance and Immunological Responses
Information source: Colorado State University
Information obtained from ClinicalTrials.gov on October 19, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Leprosy
Phase: N/A
Status: Recruiting
Sponsored by: Colorado State University Official(s) and/or principal investigator(s):
Varalakshmi Vissa, PhD, Principal Investigator, Affiliation: Colorado State University
Nora Cardona-Castro, MD, MSc, Principal Investigator, Affiliation: Instituto Colombiano de Medicina Tropical - Universidad CES
Overall contact:
Nora Cardona-Castro, Phone: +574 3014300
Summary
The purpose of this study is to determine what factors contribute to the continued incidence
of leprosy in Colombia. Study participants will include volunteering and consenting
individuals, older than 4 years of age, representing three study groups:
1. healthy persons with no known contact with leprosy patients
2. patients reporting at Instituto Colombiano de Medicina Tropical-CES and Impresa Social
del Estado Sanatorio Agua de Dios with a new diagnosis of leprosy or relapse of leprosy
3. household contacts of leprosy patients described in group 2. Blood, nasal swabs, slit
skin smears, and biopsies will be taken from the volunteers to learn the strains of
leprosy-causing bacteria in the area, the immune responses (body's response to disease)
in local residents against the bacteria, and the pattern of leprosy transmission.
Individuals will participate in this study for 1-10 days, and the study will last for 3
years.
Clinical Details
Official title: Molecular Epidemiology of Leprosy in Colombia
Study design: Cohort, Cross-Sectional
Primary outcome: Strain typing: identification of genotypes
Detailed description:
The overall objectives of this study are to understand the factors leading to continued
incidence of leprosy in Colombia by novel molecular methodologies using a combination of
retrospective and prospective sampling approaches using three study groups. Specific
objectives are: (1) strain typing of M. leprae isolates obtained from newly diagnosed
leprosy patients and household contacts (HHCs) in Colombia to identify clusters and
transmission patterns when combined with conventional epidemiological criteria; (2) to
determine the viability of M. leprae by mRNA detection in specimens collected from new
leprosy patients and HHCs; (3) to identify and determine the extent of mutations conferring
resistance in past and circulating M. leprae isolates from leprosy patients to two Multidrug
therapy (MDT) drugs; dapsone and rifampicin; (4) to detect chains of transmission in endemic
populations by a retrospective analyses of isolates in sample banks when combined with
strain typing information from new cases and conventional epidemiological criteria; and (5)
to detect, compare, and delineate immune response profiles to M. leprae antigens as
biomarkers for early detection of leprosy and prediction of clinical outcome (susceptible,
infected, and resistant individuals) among three study groups. Study participants for
prospective sample collections will include volunteering and consenting individuals older
than 4 years of age, representing three study groups: (1) healthy persons with no known
contacts with leprosy patients, (2) patients reporting at Instituto Colombiano de Medicina
Tropical-CES (ICMT-CES) and Impresa Social del Estado Sanatorio Agua de Dios for the
diagnosis of leprosy and/or relapse of leprosy, and (3) household contacts (HHC) of leprosy
patients reporting at Instituto Colombiano de Medicina Tropical-CES (ICMT-CES) and Impresa
Social del Estado Sanatorio Agua de Dios. Blood, nasal swabs, slit skin smears and biopsies
will be obtained prospectively from individuals greater than 4 years of age representing
three study groups: newly diagnosed and relapse leprosy patients, their household contacts;
and healthy persons with no known contacts with leprosy patients. Retrospective archived
samples from past and present leprosy patients will be included when available. DNA and RNA
based methodologies will be developed and applied to obtain data necessary for
substantiation of a number of factors implicated in transmission of leprosy in Colombia.
Nucleic acid based molecular methods like Multiple Locus Variable number of tandem repeat
Analysis (MLVA) and Single Nucleotide Polymorphisms (SNPs) will be performed for strain
typing M. leprae, in combination with epidemiological information to delineate the
distribution of types of the organism in various regions of Colombia. Other DNA markers such
as mutations causing drug resistance will also be collected from the M. leprae containing
specimens. Due to the lack of methods to cultivate M. leprae, viability of the organism in
newly collected biological samples will be tested by mRNA detection. A database will be
generated which will include M. leprae genotypes, patient history (clinical and demographic)
for comprehensive epidemiological analyses to monitor prevailing M. leprae population
structures reflective of short and long range dissemination; and correlations between
disease type and genotype; to track evolutionary and transmission patterns. Profiling of
host immunological responses during infection with M. leprae will be done by detection of a
panel of cytokines at the level of mRNA and/or protein, and detection of antibodies against
M. leprae antigens in leprosy patients, their household contacts and healthy individuals
with no known history or contacts with leprosy patients.
Eligibility
Minimum age: 18 Years.
Maximum age: 70 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- All leprosy patients (Group1), their household contacts (Group 2) and healthy persons
with no known contacts with leprosy patients (Group 3), between the ages of 18 and 70
years willing to participate in this study.
Exclusion Criteria:
- Patients unwilling to participate or unable to give informed consent will be excluded
from the study.
- Pregnant women will be excluded.
Exclusion criteria for objective A. 5 are one or more of the following conditions:
- Chronic illnesses such as cancer
- Diabetes
- Hepatitis
- HIV
- Tuberculosis
- Undergoing corticosteroid therapy
- Current or previous history of immunosuppressive therapy as assessed from medical
records and interviews with a physician.
Locations and Contacts
Nora Cardona-Castro, Phone: +574 3014300
Instituto Colombiano de Medicina Tropical-CES, Sabaneta, Colombia; Recruiting
Impresa Socail del Estado Sanatorio Agua de Dios, Agua de Dios City, Colombia; Recruiting
Additional Information
Starting date: April 2006
Ending date: December 2010
Last updated: August 19, 2009
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