OPTImizing MIltefosine Treatment for Cutaneous LEISHmaniasis Patients (OPTIMILEISH)

July 16, 2024 updated by: Institute of Tropical Medicine, Belgium
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Ethiopia
      • Addis Abeba, Ethiopia
        • Recruiting
        • Africa Leprosy, Tuberculosis, Rehabilitation and Training (ALERT) Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

N/A

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

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
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
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
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Miltefosine plasma concentrations - Area under the plasma concentration versus time curve (AUC)
Time Frame: Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 180
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)
Time Frame: Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 180
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)
Time Frame: Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 180
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Parasite kinetics in blood and skin
Time Frame: Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 180
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
Time Frame: Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 180
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
Time Frame: Day 28, day 90 and day 180
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
Time Frame: Day 28
Side-effects: number and proportion of patients with adverse events
Day 28

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
To explore optimization of outcome assessment using a 3D scanner
Time Frame: Day 28, Day 90, Day 180
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
Time Frame: Nutritional status at Day 0, outcome at Day 90/Day 180
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
Time Frame: Helminth infection at Day 0, outcome at Day 90/Day 180
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
Time Frame: Day 0, Day 28/Day 42/Day 56, unscheduled visit
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
Time Frame: Day 28/Day 42/Day 56
Measured by LC-MS/MS
Day 28/Day 42/Day 56

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Institute of Tropical Medicine, Belgium

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Uppsala University
The Netherlands Cancer Institute
Armauer Hansen Research Institute, Ethiopia
Alert Hospital, Ethiopia

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Saskia Van Henten, Institute of Tropical Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 18, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 30, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 30, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 20, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 16, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 23, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 23, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 16, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1708/23

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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