Ignite Creation Date:
2025-12-25 @ 2:02 AM
Ignite Modification Date:
2026-01-08 @ 11:16 AM
Study NCT ID:
NCT06514560
Status:
RECRUITING
Last Update Posted:
2024-07-23
First Post:
2024-06-20
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
OPTImizing MIltefosine Treatment for Cutaneous LEISHmaniasis Patients
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D016773', 'term': 'Leishmaniasis, Cutaneous'}], 'ancestors': [{'id': 'D007896', 'term': 'Leishmaniasis'}, {'id': 'D056986', 'term': 'Euglenozoa Infections'}, {'id': 'D011528', 'term': 'Protozoan Infections'}, {'id': 'D010272', 'term': 'Parasitic Diseases'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D012876', 'term': 'Skin Diseases, Parasitic'}, {'id': 'D000079426', 'term': 'Vector Borne Diseases'}, {'id': 'D012874', 'term': 'Skin Diseases, Infectious'}, {'id': 'D012871', 'term': 'Skin Diseases'}, {'id': 'D017437', 'term': 'Skin and Connective Tissue Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C039128', 'term': 'miltefosine'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': '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'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 80}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2024-06-18', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-07', 'completionDateStruct': {'date': '2026-12-30', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2024-07-16', 'studyFirstSubmitDate': '2024-06-20', 'studyFirstSubmitQcDate': '2024-07-16', 'lastUpdatePostDateStruct': {'date': '2024-07-23', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2024-07-23', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-12-30', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'To explore optimization of outcome assessment using a 3D scanner', 'timeFrame': 'Day 28, Day 90, Day 180', 'description': 'Machine learning models will be built to explore accuracy (% correctly predicted) of 3D scanning models to predict clinical outcomes.'}, {'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', 'description': 'Logistic regression models will be made with clinical cure/no cure as outcome, and nutritional status measured through Z-scores as predictor.'}, {'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', 'description': '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.'}, {'measure': 'To explore sequencing to detect intrinsic and acquired resistance markers for miltefosine', 'timeFrame': 'Day 0, Day 28/Day 42/Day 56, unscheduled visit', 'description': 'Whole genome sequencing will be done at AHRI to check for intrinsic (before treatment samples) and acquired resistance (relapse and end of treatment samples).'}, {'measure': 'To explore skin tissue miltefosine concentrations', 'timeFrame': 'Day 28/Day 42/Day 56', 'description': 'Measured by LC-MS/MS'}], 'primaryOutcomes': [{'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', 'description': '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.'}, {'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', 'description': 'Determined by LC-MS/MS, stratified by whether patients received allometric dosing or not.'}, {'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', 'description': 'Determined by LC-MS/MS, stratified by whether patients received allometric dosing or not.'}], 'secondaryOutcomes': [{'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', 'description': 'To determine parasite kinetics in terms of Ct-values in blood and skin (microbiopsy sample) measured by quantitative PCR'}, {'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', 'description': '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.'}, {'measure': 'Treatment outcomes of patients on miltefosine treatment', 'timeFrame': 'Day 28, day 90 and day 180', 'description': 'Clinical cure rate determined by complete flattening, complete reepithelization and absence of erythema, crustation, and swelling'}, {'measure': 'Assess safety of miltefosine', 'timeFrame': 'Day 28', 'description': 'Side-effects: number and proportion of patients with adverse events'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Cutaneous Leishmaniases']}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'minimumAge': '2 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'A total of 40 children on allometric dosing and 40 other patients will be enrolled in the study', 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Clinical or parasitological (microscopy or PCR) confirmation of leishmaniasis\n* Age \\>2\n* Clinical decision to start miltefosine treatment as systemic treatment\n* In case of females of child-bearing age: willing to take contraceptive for 6 months (parenteral or IUD or implant)\n* Willing and able to provide informed consent\n* Willing to be hospitalized for the duration of treatment\n\nExclusion Criteria:\n\n* Currently on treatment or having received modern treatment for leishmaniasis in the last 3 months\n* Pregnant (pregnancy test at D0) or breastfeeding\n* Unlikely to come for follow-up visits\n* 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'}, 'identificationModule': {'nctId': 'NCT06514560', 'acronym': 'OPTIMILEISH', 'briefTitle': 'OPTImizing MIltefosine Treatment for Cutaneous LEISHmaniasis Patients', 'organization': {'class': 'OTHER', 'fullName': 'Institute of Tropical Medicine, Belgium'}, 'officialTitle': 'OPTImizing MIltefosine Treatment for Cutaneous LEISHmaniasis Patients', 'orgStudyIdInfo': {'id': '1708/23'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Non-allometric dosing', 'description': '40 patients who will not use allometric dosing will be included\n\nmiltefosine will be given based on weight: 30-45 kg: 100mg miltefosine per day \\>45 kg: 150mg miltefosine per day', 'interventionNames': ['Drug: Miltefosine']}, {'label': 'allometric dosing (weight below 30 kg)', 'description': '40 patients who weigh less than 30kg and therefore get allometric dosing will be recruited.\n\nDosing is given based on weight, height, and sex, according to Dorlo et al 2012', 'interventionNames': ['Drug: Miltefosine']}], 'interventions': [{'name': 'Miltefosine', 'type': 'DRUG', 'description': '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', 'armGroupLabels': ['Non-allometric dosing', 'allometric dosing (weight below 30 kg)']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Addis Ababa', 'status': 'RECRUITING', 'country': 'Ethiopia', 'contacts': [{'name': 'Shimelis Negusse, MD', 'role': 'CONTACT', 'email': 'shimelis321@gmail.com', 'phone': '09 11642060', 'phoneExt': '+251'}], 'facility': 'Africa Leprosy, Tuberculosis, Rehabilitation and Training (ALERT) Hospital', 'geoPoint': {'lat': 9.02497, 'lon': 38.74689}}], 'centralContacts': [{'name': 'Shimelis Nigusse, MD', 'role': 'CONTACT', 'email': 'shimelis321@gmail.com', 'phone': '0911642060'}], 'overallOfficials': [{'name': 'Saskia Van Henten', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Institute of Tropical Medicine'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Institute of Tropical Medicine, Belgium', 'class': 'OTHER'}, 'collaborators': [{'name': 'Alert Hospital, Ethiopia', 'class': 'OTHER'}, {'name': 'Armauer Hansen Research Institute, Ethiopia', 'class': 'OTHER'}, {'name': 'Uppsala University', 'class': 'OTHER'}, {'name': 'The Netherlands Cancer Institute', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}