Clinical Trial Details
— Status: Recruiting
Administrative data
NCT number |
NCT06222372 |
Other study ID # |
INDIGO#2 |
Secondary ID |
|
Status |
Recruiting |
Phase |
N/A
|
First received |
|
Last updated |
|
Start date |
March 4, 2020 |
Est. completion date |
November 2025 |
Study information
Verified date |
January 2024 |
Source |
Leiden University Medical Center |
Contact |
Annemieke Geluk, PhD |
Phone |
+31715261974 |
Email |
ageluk[@]lumc.nl |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
Contact with Mycobacterium leprae (M. leprae) infected individuals is a risk factor for
development of leprosy. Thus, detection of asymtomatically M. leprae infected individuals,
allowing informed decision making on who needs treatment at a preclinical stage, is vital to
interrupt transmission and can help prevent leprosy. In a previous field trial the BCG
vaccine was applied alone and combined with a single dose of rifampin (SDR) as prophylactic
interventions in contacts of leprosy patients in Bangladesh. Concurrently, blood-derived host
immune-profiles specific for M. leprae infection or leprosy disease were assessed in the same
population by merging detection of innate, adaptive cellular as well as humoral immunity.
This has led to the identification of selected host-immune markers, currently applied in a
low complexity lateral flow assay based on up-coverting particles (UCP-LFA), providing a
convenient tool to assess M. leprae infection, allowing assessment of efficacy of
prophylactic interventions in a point-of-care setting.
The proposed study aims to determine the effect of post-exposure prophylaxis by SDR on M.
leprae infection rate using UCP-LFA before and after prophylaxis.
Description:
A stable leprosy new case detection rate in many endemic countries indicates that the
transmission of M. leprae is continuing unabated and that the current control strategy of
case finding and provision of multi drug therapy (MDT) is not sufficient. Immunoprophylaxis
by vaccination or post-exposure prophylaxis (PEP) with antibiotics provide effective
strategies for the prevention of leprosy. Prophylactic treatment with single dose rifampicin
(SDR) has shown to be a successful method to prevent leprosy in contacts of newly diagnosed
leprosy patients (1). Currently, the Leprosy Post-Exposure Prophylaxis (LPEP) program
generates evidence on the feasibility of integrating contact tracing and single-dose
rifampicin (SDR) administration into routine leprosy control activities within the national
leprosy control programmes of Brazil, Cambodia, India, Indonesia, Myanmar, Nepal, Sri Lanka
and Tanzania [Steinmann P, et al]. Recently, the world health orginazation (WHO) has endorsed
PEP for routine application in their new "Guidelines for the diagnosis, treatment and
prevention of leprosy".
Genomic and transcriptomics analysis (e.g. population- and twin studies [5]), have determined
that the host genetic background is an important risk factor for leprosy susceptibility. In
addition, close contacts of leprosy patients have a higher risk of developing the disease (2,
3), which therefore represents the primary target group for interventions (4). To target
individuals spreading leprosy bacilli for prophylactic treatment, M. leprae infection needs
to be measurable objectively. Antibody levels correspond with bacterial load and risk of
transmission. Also, individuals seropositive for anti-M. leprae phenolic glycolipid-I (PGL-I)
antibodies, are at 5-8 fold higher risk of leprosy (5, 6). Moreover, in a leprosy endemic
area in Bangladesh, we recently showed significant added value of cellular markers
(cytokines, chemokines, acute phase proteins) to identify infection (7). Thus, for
implementation in a PEP-approach, new tests that indicate who needs treatment should allow
detection of both cellular-and humoral markers.
In previous studies applying UCP-LFA in 4 countries with variable leprosy endemicity
(Bangladesh, Brazil, China and Ethiopia), we have shown that the combined assessment of serum
levels of multiple biomarkers including anti-PGL-I Ab as well as cytokines, significantly
improved the diagnostic potential for detection of M. leprae infected individuals. This
demonstrates that UCP-LFAs for detection of multiple biomarkers can provide valuable tools
for more accurate detection of M. leprae infection. Its low-complexity POC format and
applicability for use of finger-stick blood allows large scale screening efforts in field
settings. Moreover, the format of the UCP-LFA is being further developed in various other
projects (focused on tuberculosis and leprosy diagnostic tests). This has recently resulted
in a multi-biomarker test (MBT) format that allows simultaneous detection of up to 6 markers,
which is currently further evaluated in the field for tuberculosis diagnostic purposes. Since
the UCP-LFA format is flexible and can accommodate for detection of different markers, this
latest development will also enable combined detection of humoral and cellular biomarkers
which together represent a specific signature for M. leprae infection.