OPTImizing MIltefosine Treatment for Cutaneous LEISHmaniasis Patients

NCT06514560 | Recruiting

• 1 other identifier: 1708/23
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Cutaneous Leishmaniases

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (4)

• Parasite kinetics in blood and skin

  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

  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

  Day 28, day 90 and day 180

• Assess safety of miltefosine

  Day 28

Other Outcomes (5)

• To explore optimization of outcome assessment using a 3D scanner

  Day 28, Day 90, Day 180

• To explore whether nutritional status in CL patients is related to treatment outcomes

  Nutritional status at Day 0, outcome at Day 90/Day 180

• To explore whether helminth infection in CL patients is related to treatment outcomes

  Helminth infection at Day 0, outcome at Day 90/Day 180

Study Arms (2)

Non-allometric dosing

40 patients who will not use allometric dosing will be included miltefosine will be given based on weight: 30-45 kg: 100mg miltefosine per day \>45 kg: 150mg miltefosine per day

Drug: Miltefosine

allometric dosing (weight below 30 kg)

40 patients who weigh less than 30kg and therefore get allometric dosing will be recruited. Dosing is given based on weight, height, and sex, according to Dorlo et al 2012

Drug: Miltefosine

Interventions

Miltefosine DRUG

Miltefosine will be prescribed by the treating physician for a minimum of 4 weeks. If treatment response is not sufficient, treatment extension could be decided by the treating physician up to 8 weeks

Non-allometric dosing; allometric dosing (weight below 30 kg)

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Institute of Tropical Medicine, Belgium: lead
• Alert Hospital, Ethiopia: collaborator
• Armauer Hansen Research Institute, Ethiopia: collaborator
• Uppsala University: collaborator
• The Netherlands Cancer Institute: collaborator

Study Sites (1)

Africa Leprosy, Tuberculosis, Rehabilitation and Training (ALERT) Hospital

Addis Ababa, Ethiopia

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Dried blood spots for PK analysis Microbiopsy from skin for PCR analysis Routine Skin slit smear for genomic sequencing optional 2mm punch biopsy for PK analysis optional microbiopsy for PK analysis Serum sample for biobanking WB sample for biobanking

MeSH Terms

Conditions

Leishmaniasis, Cutaneous

Interventions

miltefosine

Condition Hierarchy (Ancestors)

Leishmaniasis; Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Skin Diseases, Parasitic; Vector Borne Diseases; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Saskia Van Henten

  Institute of Tropical Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shimelis Nigusse, MD

CONTACT

0911642060; shimelis321@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2024
• First Posted: July 23, 2024
• Study Start: June 18, 2024
• Primary Completion: December 30, 2025
• Study Completion (Estimated): December 30, 2026
• Last Updated: July 23, 2024

Record last verified: 2024-07

Locations

ET (1)