Disulfiram repurposing in the combined chemotherapy of Chagas disease A protocol for phase I/II clinical trial

dc.creatorSaraiva, Roberto Magalhães
dc.creatorPortela, Luciana Fernandes
dc.creatorSilveira, Gabriel Parreiras Estolano da
dc.creatorGomes, Natalia Lins da Silva
dc.creatorPInto, Douglas Pereira
dc.creatorSilva, Aline Campos de Azevedo da
dc.creatorSangenis, Luiz Henrique Conde
dc.creatorCarneiro, Fernanda Martins
dc.creatorSilva, Juliana Almeida
dc.creatorMarinho, Patricia Wink
dc.creatorSilva, Gilberto Marcelo Sperandio
dc.creatorEstrela, Rita de Cássia Elias
dc.creatorHasslocher-Moreno, Alejandro Marcel
dc.creatorMediano, Mauro Felippe Felix
dc.creatorMoreira, Otacilio C.
dc.creatorBrito, Constança
dc.creatorChavez-Perez, Sandra Aurora
dc.creatorViçosa, Alessandra Lifsitch
dc.creatorSuarez-Fontes, Ana Márcia
dc.creatorVannier-Santos, Marcos André
dc.date2021-08-27T17:22:49Z
dc.date2021-08-27T17:22:49Z
dc.date2021
dc.date.accessioned2023-09-26T22:38:44Z
dc.date.available2023-09-26T22:38:44Z
dc.identifierSARAIVA, Roberto Magalhães et al. Disulfiram repurposing in the combined chemotherapy of Chagas Disease. A protocol for phase I/II clinical trial. Medicine Case Reports and Study Protocols, v. 2, n. 7, p. 1-8, 2021.
dc.identifier2589-8647
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/48781
dc.identifier10.1097/MD9.0000000000000110
dc.identifier2589-8655
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8881428
dc.descriptionBackground: Chagas disease (CD) has high morbimortality and the available trypanocidal treatment, including benznidazole (BZ), has limited efficacy in chronic patients. Furthermore, BZ causes adverse effects (AE) that prevent treatment completion in up to 30% of patients. The use of repositioned drugs or drug combination may provide an effective trypanocidal treatment. Disulfiram (DF) may enhance BZ activity and decrease BZ related AE. This study aims to assess the safety of a new combination of drugs for CD therapy, assuming BZ as the drug of choice plus DF as repositioned drug. Methods: This single-centre, open-label, phase I/II clinical trial was designed to evaluate the safety of the combined use of BZ plus DF for CD therapy. Participants are adults with indeterminate form of chronic CD, both sexes, aged from 18 to 70 years old and Trypanosoma cruzi polymerase chain reaction-positive. The primary outcome will be the occurrence of serious AE. The secondary outcome will be post-treatment Trypanosoma cruzi polymerase chain reaction negativization. Six groups of 9 patients will be sequentially tested. The first group will be allocated to receive BZ 100mg/d + DF 250mg/d for 60 days. Upon safety confirmation (<1/3 of participants with serious AE), the combination dose will be gradually increased and dispensed to 5 groups (group II:BZ 200mg/day+DF 250mg/d; group III:BZ 300mg/d + DF 250mg/d; group IV:BZ 100mg/d + DF 500mg/d; group V:BZ 200mg/d + DF 500mg/d; group VI: BZ 300mg/d + DF 500mg/d) for 60 days in order to determine the maximum tolerated dose. Discussion: Our hypothesis is that the drug combination will be well tolerated and allow the proposal of phase II trials in larger scale to test the efficacy of the new drug combination in CD. We expect that the studied combination will have less AEs with an efficacy.
dc.formatapplication/pdf
dc.languageeng
dc.publisherMedicine Case Reports and Study Protocol
dc.rightsopen access
dc.subjectDoença de Chagas
dc.subjectQuimioterapia
dc.subjectDisulfiram
dc.subjectReaproveitamento de drogas
dc.subjectProtocolo
dc.subjectEnsaio clínico de fase I / II
dc.subjectChagas disease
dc.subjectChemotherapy
dc.subjectDisulfiram repurposing
dc.subjectProtocol
dc.subjectPhase I/II clinical trial
dc.titleDisulfiram repurposing in the combined chemotherapy of Chagas disease A protocol for phase I/II clinical trial
dc.typeArticle


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