Spatial Analysis of Host-parasite Interactions in Cutaneous Leishmaniasis in Ethiopia

NCT ID: NCT05332093

Last Updated: 2025-01-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

92 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-03-21

Study Completion Date

2024-12-31

Brief Summary

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Cutaneous leishmaniasis manifestations range from self-healing localized skin ulcers/nodules to diffusely spread chronic lesions. Knowledge on the host-parasite interactions underpinning the different clinical presentations is scarce, in particular for L. aethiopica infections where disease can be extremely severe. Our aim is to define differences in skin immune responses and parasite virulence in CL patients at single cell/parasite level and how it underpins the different clinical presentations (localised, mucocutaneous and diffuse), by producing the first spatially-resolved 'ecological' map of the lesions.

Detailed Description

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Specific objectives:

1. To profile the full heterogeneity in skin and lesion immunity (single cell RNAseq), and the cellular microenvironment surrounding infected and non-infected macrophages (digital spatial profiling).
2. To study the genomic diversity of L. aethiopica and identify features associated with the different clinical presentations (whole genome sequencing).
3. To understand how parasites respond to the microenvironmental conditions and define parasite survival niches (digital spatial profiling).
4. Study metabolic determinants of skin immunity (e.g. lipid metabolism, bioenergetics, short-chain fatty acids) in the context of key structural features of the skin landscape known to influence local metabolism and immune response (e.g. adipose tissue, follicles, microvasculature) (SpatialOMx).
5. To investigate the association between patient outcomes and the above host/parasite factors at baseline.

Conditions

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Cutaneous Leishmaniases

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Local cutaneous leishmaniasis patients group (LCL)

local cutaneous leishmaniasis patients

skin biopsy

Intervention Type DIAGNOSTIC_TEST

4mm skin biopsy

venous blood sample (plasma, PBMC, WB)

Intervention Type DIAGNOSTIC_TEST

venous blood sample to acquire plasma, PBMCs and whole blood

venous blood sample (HLA)

Intervention Type GENETIC

venous blood sample used for HLA typing

skin slit

Intervention Type GENETIC

genome sequencing of parasite DNA that is extracted from the skin slit

Mucocutaneous leishmaniasis patients group (MCL)

mucocutaneous leishmaniasis patients

skin biopsy

Intervention Type DIAGNOSTIC_TEST

4mm skin biopsy

venous blood sample (plasma, PBMC, WB)

Intervention Type DIAGNOSTIC_TEST

venous blood sample to acquire plasma, PBMCs and whole blood

venous blood sample (HLA)

Intervention Type GENETIC

venous blood sample used for HLA typing

skin slit

Intervention Type GENETIC

genome sequencing of parasite DNA that is extracted from the skin slit

Diffuse cutaneous leishmaniasis patients group (DCL)

diffuse cutaneous leishmaniasis patients

skin biopsy

Intervention Type DIAGNOSTIC_TEST

4mm skin biopsy

venous blood sample (plasma, PBMC, WB)

Intervention Type DIAGNOSTIC_TEST

venous blood sample to acquire plasma, PBMCs and whole blood

venous blood sample (HLA)

Intervention Type GENETIC

venous blood sample used for HLA typing

skin slit

Intervention Type GENETIC

genome sequencing of parasite DNA that is extracted from the skin slit

Healthy control patients group Ethiopia (HC - Ethiopia)

healthy control patients undergoing elective surgery in Northern Ethiopia

skin biopsy

Intervention Type DIAGNOSTIC_TEST

4mm skin biopsy

Healthy control patients group Belgium (HC - Belgium)

healthy control patients undergoing plastic surgery in Belgium

skin biopsy

Intervention Type DIAGNOSTIC_TEST

4mm skin biopsy

Interventions

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skin biopsy

4mm skin biopsy

Intervention Type DIAGNOSTIC_TEST

venous blood sample (plasma, PBMC, WB)

venous blood sample to acquire plasma, PBMCs and whole blood

Intervention Type DIAGNOSTIC_TEST

venous blood sample (HLA)

venous blood sample used for HLA typing

Intervention Type GENETIC

skin slit

genome sequencing of parasite DNA that is extracted from the skin slit

Intervention Type GENETIC

Eligibility Criteria

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Inclusion Criteria

* Willing and able to provide informed consent
* Clinically confirmed CL diagnosis
* Between 12 and 50 years of age

Exclusion Criteria

* Difficult or too painful sampling zone (see skin biopsy procedure below)
* (Primary) lesion size \< 1 cm
* Already receiving CL treatment or received CL treatment in the last 3 months (excluding traditional medicine)
* Known major comorbidity at time of diagnosis (e.g. VL, HIV, TB, malaria, severe intestinal helminth infection)
* Medical history of VL
* Severely underweight (BMI\<16)
* Known pregnancy
* Use of immunosuppressive medication in the last month
* Known excessive alcohol use (between \>10 intakes/day and \>10 intakes/week)
* History of hypersensitivity to local anaesthetics
* Presence of keloids/hypertrophic scars
Minimum Eligible Age

12 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Gondar

OTHER

Sponsor Role collaborator

University of York

OTHER

Sponsor Role collaborator

Maastricht University

OTHER

Sponsor Role collaborator

University Hospital, Antwerp

OTHER

Sponsor Role collaborator

Institute of Tropical Medicine, Belgium

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Wim Adriaensen, PhD

Role: PRINCIPAL_INVESTIGATOR

Institute of Tropical Medicine Antwerp

Mikias Woldetensay, MD

Role: PRINCIPAL_INVESTIGATOR

University of Gondar

Locations

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University of Gondar

Gonder, Amhara, Ethiopia

Site Status

Countries

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Ethiopia

Other Identifiers

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1451/20

Identifier Type: -

Identifier Source: org_study_id

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