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

Cutaneous Leishmaniases Clinical Trial

— SpatialCL  

Official title:

Spatial Analysis of Host-parasite Interactions in the Skin Across the Clinical Spectrum of Cutaneous Leishmaniasis in Ethiopia

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05332093
• Other study ID #: 1451/20
• Status: Active, not recruiting
• Start date: March 21, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: April 2024
• Source: Institute of Tropical Medicine, Belgium
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 92
• Est. completion date: December 31, 2024
• Est. primary completion date: March 30, 2024
• Gender: All
• Age group: 12 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Cutaneous Leishmaniases
• Leishmaniasis
• Leishmaniasis, Cutaneous

Intervention

Diagnostic Test:
• skin biopsy
4mm skin biopsy
• venous blood sample (plasma, PBMC, WB)
venous blood sample to acquire plasma, PBMCs and whole blood

Genetic:
• venous blood sample (HLA)
venous blood sample used for HLA typing
• skin slit
genome sequencing of parasite DNA that is extracted from the skin slit

Locations

Country	Name	City	State
Ethiopia	University of Gondar	Gondar	Amhara

Sponsors (5)

Lead Sponsor	Collaborator
Institute of Tropical Medicine, Belgium	Maastricht University, University Hospital, Antwerp, University of Gondar, University of York

Country where clinical trial is conducted

Ethiopia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Spatially resolved immunological characterization of the CL lesion using single cell RNA sequencing and digital spatial profiling	Using single cell RNA sequencing and digital spatial profiling methods, we will profile the full heterogeneity in healthy skin/lesion immunity and the cellular microenvironment surrounding infected and non-infected macrophages, respectively.	Day 0
Primary	Genomic characterization of L. aethiopica using whole genome sequencing	Whole genome sequencing will allow us to study the genomic diversity of L. aethiopica and identify features associated with the different clinical presentations.	Day 0
Primary	Defining microenvironment and parasite niches in CL lesions using digital spatial profiling	The digital spatial profiling will indicate the different microenvironmental conditions and parasite survival niches.	Day 0
Primary	Spatially resolved determination of the metabolic profile of the CL lesion using spatial OMx	The 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) will be studied by SpatialOMx.	Day 0
Primary	The association between host/parasite factors and patients after treatment using clinical parameters	Patients are clinically assessed at day 0 (baseline visit), day 28 and month 6. These clinical assessments include a medical questionnaire and lesion assessment, and are compared with the single cell RNA sequencing and spatial resolution data to define potential causal relations between patient outcomes and immunometabolic factors.	Month 6

External Links

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