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Spatial Analysis of Host-parasite Interactions in Cutaneous Leishmaniasis in Ethiopia (SpatialCL)

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ClinicalTrials.gov Identifier: NCT05332093
Recruitment Status : Recruiting
First Posted : April 18, 2022
Last Update Posted : May 22, 2023
Sponsor:
Collaborators:
University of Gondar
Wollo University
University of York
Maastricht University
University Hospital, Antwerp
Information provided by (Responsible Party):
Institute of Tropical Medicine, Belgium

Brief 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.

Condition or disease Intervention/treatment
Cutaneous Leishmaniases Diagnostic Test: skin biopsy Diagnostic Test: venous blood sample (plasma, PBMC, WB) Genetic: venous blood sample (HLA) Genetic: skin slit

Detailed 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.

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 200 participants
Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration: 6 Months
Official Title: Spatial Analysis of Host-parasite Interactions in the Skin Across the Clinical Spectrum of Cutaneous Leishmaniasis in Ethiopia
Actual Study Start Date : March 21, 2022
Estimated Primary Completion Date : September 30, 2023
Estimated Study Completion Date : December 30, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leishmaniasis

Group/Cohort Intervention/treatment
Local cutaneous leishmaniasis patients group (LCL)
local cutaneous leishmaniasis patients
Diagnostic Test: skin biopsy
4mm skin biopsy

Diagnostic Test: 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

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

Mucocutaneous leishmaniasis patients group (MCL)
mucocutaneous leishmaniasis patients
Diagnostic Test: skin biopsy
4mm skin biopsy

Diagnostic Test: 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

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

Diffuse cutaneous leishmaniasis patients group (DCL)
diffuse cutaneous leishmaniasis patients
Diagnostic Test: skin biopsy
4mm skin biopsy

Diagnostic Test: 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

Genetic: skin slit
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
Diagnostic Test: skin biopsy
4mm skin biopsy

Healthy control patients group Belgium (HC - Belgium)
healthy control patients undergoing plastic surgery in Belgium
Diagnostic Test: skin biopsy
4mm skin biopsy




Primary Outcome Measures :
  1. Spatially resolved immunological characterization of the CL lesion using single cell RNA sequencing and digital spatial profiling [ Time Frame: Day 0 ]
    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.

  2. Genomic characterization of L. aethiopica using whole genome sequencing [ Time Frame: Day 0 ]
    Whole genome sequencing will allow us to study the genomic diversity of L. aethiopica and identify features associated with the different clinical presentations.

  3. Defining microenvironment and parasite niches in CL lesions using digital spatial profiling [ Time Frame: Day 0 ]
    The digital spatial profiling will indicate the different microenvironmental conditions and parasite survival niches.

  4. Spatially resolved determination of the metabolic profile of the CL lesion using spatial OMx [ Time Frame: Day 0 ]
    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.

  5. The association between host/parasite factors and patients after treatment using clinical parameters [ Time Frame: Month 6 ]
    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.


Biospecimen Retention:   Samples With DNA
Blood, stool and skin samples will be isolated from CL patients and solely skin samples from healthy controls.


Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years to 40 Years   (Child, Adult)
Sexes Eligible for Study:   All
Sampling Method:   Probability Sample
Study Population
Patients presenting at the LRTC and Boru Meda Hospital with clinically suspected CL during the study period will be screened for eligibility. Suspicion for CL is assessed by physicians as per routine care. In general, children are included in the study population since they are commonly affected, and also make up the majority of DCL patients.
Criteria

Inclusion Criteria:

  • Willing and able to provide informed consent
  • Clinically confirmed CL diagnosis
  • Between 12 and 40 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05332093


Contacts
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Contact: Thao-Thy Pham, PhD +32474642614 thaothypham@itg.be
Contact: Wim Adriaensen, PhD +32 494 75 53 60 wadriaensen@itg.be

Locations
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Ethiopia
University of Gondar Recruiting
Gondar, Amhara, Ethiopia, 6200
Contact: Mikias Woldetensay, MD    +251911435963    mikiaswoldetensay@gmail.com   
Contact: Silamsaw Asrem Mezgebu, Ms    +251921576259    msilamsaw@gmail.com   
Sponsors and Collaborators
Institute of Tropical Medicine, Belgium
University of Gondar
Wollo University
University of York
Maastricht University
University Hospital, Antwerp
Investigators
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Principal Investigator: Wim Adriaensen, PhD Institute of Tropical Medicine Antwerp
Principal Investigator: Annisa Befekadu Tesfaye, MD University of Gondar
Principal Investigator: Seid Getahun, MD Wollo University
Principal Investigator: Mikias Woldetensay, MD University of Gondar
Additional Information:
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Responsible Party: Institute of Tropical Medicine, Belgium
ClinicalTrials.gov Identifier: NCT05332093    
Other Study ID Numbers: 1451/20
First Posted: April 18, 2022    Key Record Dates
Last Update Posted: May 22, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD accessible by managed access
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: After completion of the primary publication
Access Criteria: Applicants will need to fill out a data access request form
URL: https://www.itg.be/E/data-sharing-open-access

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Institute of Tropical Medicine, Belgium:
leishmania
leishmaniasis
cutaneous leishmaniasis
neglected tropical disease
immunoparasitology
Additional relevant MeSH terms:
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Leishmaniasis
Leishmaniasis, Cutaneous
Euglenozoa Infections
Protozoan Infections
Parasitic Diseases
Infections
Skin Diseases, Parasitic
Vector Borne Diseases
Skin Diseases, Infectious
Skin Diseases