OPTImizing MIltefosine Treatment for Cutaneous LEISHmaniasis Patients
NCT Number: NCT06514560
Acronym: OPTIMILEISH
Status: RECRUITING
Study Type: OBSERVATIONAL
Conditions: Cutaneous Leishmaniases
Interventions: DRUG: Miltefosine
Sponsor: Institute of Tropical Medicine, Belgium
Collaborators: Alert Hospital, Ethiopia|Armauer Hansen Research Institute, Ethiopia|Uppsala University|The Netherlands Cancer Institute
Sex: ALL
Age: CHILD, ADULT, OLDER_ADULT
Enrollment: 80
Study Design: Observational Model: |Time Perspective: p
Start Date: 2024-06-18
Completion Date: 2026-12-30
Locations: Africa Leprosy, Tuberculosis, Rehabilitation and Training (ALERT) Hospital, Addis Abeba, Ethiopia

Summary:
While there are indications that 28 days of miltefosine is not sufficient for treating CL by L. aethiopica, a better understanding of what happens in terms of parasite clearance and drug dosing is lacking. In this study, longitudinal measurements of parasite and drug concentrations during treatment are done to monitor parasite kinetics as well as pharmacokinetics. This data will be crucial to provide more information on duration and dosing of miltefosine in CL patients globally, and in Ethiopia and pediatric patients in particular.

Primary Outcome Measures: Miltefosine plasma concentrations - Area under the plasma concentration versus time curve (AUC), Determined by LC-MS/MS, miltefosine pharmacokinetics are assessed through calculation of the area under the plasma concentration-time curve from start of treatment until end of treatment (AUC0-EoT), stratified by whether patients received allometric dosing or not., Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 180|Miltefosine plasma concentrations - Maximum plasma concentration (Cmax), Determined by LC-MS/MS, stratified by whether patients received allometric dosing or not., Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 180|MIltefosine plasma concentrations - Time of maximum concentration (Tmax), Determined by LC-MS/MS, stratified by whether patients received allometric dosing or not., Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 180
Secondary Outcome Measures: Parasite kinetics in blood and skin, To determine parasite kinetics in terms of Ct-values in blood and skin (microbiopsy sample) measured by quantitative PCR, Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 180|Adapted allometric dosing scheme specifically for children with CL, Population PK and PK-PD analysis of the relationship between miltefosine exposure and parasite kinetics will be done at UU, based on results from miltefosine plasma concentrations. Structural pharmacokinetic modelling will be used to develop and simulate alternative dosing schemes for children with CL, using Monte Carlo simulations., Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 180|Treatment outcomes of patients on miltefosine treatment, Clinical cure rate determined by complete flattening, complete reepithelization and absence of erythema, crustation, and swelling, Day 28, day 90 and day 180|Assess safety of miltefosine, Side-effects: number and proportion of patients with adverse events, Day 28
Other Outcome Measures: To explore optimization of outcome assessment using a 3D scanner, Machine learning models will be built to explore accuracy (% correctly predicted) of 3D scanning models to predict clinical outcomes., Day 28, Day 90, Day 180|To explore whether nutritional status in CL patients is related to treatment outcomes, Logistic regression models will be made with clinical cure/no cure as outcome, and nutritional status measured through Z-scores as predictor., Nutritional status at Day 0, outcome at Day 90/Day 180|To explore whether helminth infection in CL patients is related to treatment outcomes, Logistic regression models will be made with clinical cure/no cure as outcome, and helminth infection (determined as present/not present by wet mount stool exam) as predictor., Helminth infection at Day 0, outcome at Day 90/Day 180|To explore sequencing to detect intrinsic and acquired resistance markers for miltefosine, Whole genome sequencing will be done at AHRI to check for intrinsic (before treatment samples) and acquired resistance (relapse and end of treatment samples)., Day 0, Day 28/Day 42/Day 56, unscheduled visit|To explore skin tissue miltefosine concentrations, Measured by LC-MS/MS, Day 28/Day 42/Day 56