Clinical trial NCT06514560: OPTImizing MIltefosine Treatment for Cutaneous LEISHmaniasis Patients
Official title: OPTImizing MIltefosine Treatment for Cutaneous LEISHmaniasis Patients
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cutaneous Leishmaniases
Lead sponsor: Institute of Tropical Medicine, Belgium
Sponsor class: OTHER
Collaborators: name: Alert Hospital, Ethiopia
name: Armauer Hansen Research Institute, Ethiopia
name: Uppsala University
name: The Netherlands Cancer Institute
First posted: 2024-07-23
Enrollment: 80
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: A total of 40 children on allometric dosing and 40 other patients will be enrolled in the study

Brief 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.

Detailed description: In this project, parasite dynamics and miltefosine pharmacokinetics in the skin and blood during routine durations of miltefosine treatment (4-8 weeks) are studied with the aim to provide evidence to optimize miltefosine dosing for treatment of CL. By also studying these factors in children who get allometric miltefosine dosing, data which can be used to adapt the current allometric dosing scheme specifically to children with CL will be produced. Exploratory objectives will look into searching for more objective outcome assessment measures, resistance, helminth infection and nutritional status as potential factors affecting treatment response.

Eligibility criteria: Inclusion Criteria:

* Clinical or parasitological (microscopy or PCR) confirmation of leishmaniasis
* Age \>2
* Clinical decision to start miltefosine treatment as systemic treatment
* In case of females of child-bearing age: willing to take contraceptive for 6 months (parenteral or IUD or implant)
* Willing and able to provide informed consent
* Willing to be hospitalized for the duration of treatment

Exclusion Criteria:

* Currently on treatment or having received modern treatment for leishmaniasis in the last 3 months
* Pregnant (pregnancy test at D0) or breastfeeding
* Unlikely to come for follow-up visits
* Abnormal lab values Hemoglobin \<5.0g/100mL Platelets \<50 x 10\^9/L White blood count \<1 x 10\^9/L ASAT/ALAT \>3x upper normal range Creatinine above the normal limit

Primary outcomes:
measure: Miltefosine plasma concentrations - Area under the plasma concentration versus time curve (AUC)
timeFrame: Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 180
measure: Miltefosine plasma concentrations - Maximum plasma concentration (Cmax)
timeFrame: Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 180
measure: MIltefosine plasma concentrations - Time of maximum concentration (Tmax)
timeFrame: Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 180
Secondary outcomes:
measure: Parasite kinetics in blood and skin
timeFrame: Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 180
measure: Adapted allometric dosing scheme specifically for children with CL
timeFrame: Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 180
measure: Treatment outcomes of patients on miltefosine treatment
timeFrame: Day 28, day 90 and day 180
measure: Assess safety of miltefosine
timeFrame: Day 28
Other outcomes:
measure: To explore optimization of outcome assessment using a 3D scanner
timeFrame: Day 28, Day 90, Day 180
measure: To explore whether nutritional status in CL patients is related to treatment outcomes
timeFrame: Nutritional status at Day 0, outcome at Day 90/Day 180
measure: To explore whether helminth infection in CL patients is related to treatment outcomes
timeFrame: Helminth infection at Day 0, outcome at Day 90/Day 180
measure: To explore sequencing to detect intrinsic and acquired resistance markers for miltefosine
timeFrame: Day 0, Day 28/Day 42/Day 56, unscheduled visit
measure: To explore skin tissue miltefosine concentrations
timeFrame: Day 28/Day 42/Day 56
Locations:
city: Addis Abeba
country: Ethiopia
facility: Africa Leprosy, Tuberculosis, Rehabilitation and Training (ALERT) Hospital
Study officials:
affiliation: Institute of Tropical Medicine
name: Saskia Van Henten
role: PRINCIPAL_INVESTIGATOR
References: