Oxfendazole in Mild Parenchymal Brain Cysticercosis

Official title

A Double-blind Multicenter, Randomized Controlled Trial of Single and Multiple Dose Regimens of Oxfendazole for Mild (One or Two Lesions) Parenchymal Brain Cysticercosis, With an Open Comparison Group

Overview

The goal of this clinical trial is to compare a single and multiple dose regimens of oxfendazole with the standard treatment in patients with mild (one or two lesions) parenchymal brain cysticercosis. The main question it aims to answer is if OXF will enhance clearance of brain parasites and therefore provide greater cysticidal efficacy, with the potential to provide a single-dose therapy for this type of NCC. The study cohort will also allow us to identify early imaging markers that predict lesion resolution, as well as factors associated with residual calcification or focal gliosis after lesion resolution. This study will also provide additional information on the safety of the study interventions.

Detailed description

This three-arm randomized controlled phase II/III clinical trial will compare the efficacy and safety of a single-dose regimen with 20 mg/kg oxfendazole and a regimen with three similar doses spread over seven days (day 1, day 4 and day 7), with the most effective antiparasitic regimen available, combined albendazole plus praziquantel for ten days in individuals with mild NCC (with one to two lesions).

Participants will receive treatment with oxfendazole (one or three dose regimens) or the standard treatment (albendazole + praziquantel). At day 15 after treatment onset, an MRI will be performed to evaluate early predictors of lesion resolution. MRI at day 90 will serve to evaluate efficacy (lesion resolution) and a day 180 MRI will evaluate sequelae lesions. CT will be performed at the en of the study to confirm persistence of calcified sequelae lesion.

The study will enroll 544 patients with viable or degenerating parenchymal NCC with no more than two lesions, all in a single brain area. Lesions can be one or two adjacent, viable or degenerating NCC lesions. Patients with only calcified lesions will not be included even if they show perilesional contrast enhancement.

Interventions

• Drug Oxfendazole single dose
  Subjects will receive active oxfendazole, 20 mg/kg/day, orally, as a single dose. Oxfendazole placebo will be used at days 4 and 7 to maintain blinding between the two intervention arms.
• Drug Oxfendazole three doses
  Subjects will receive active oxfendazole, 20 mg/kg/day, orally, in three days (1, 4 and 7)
• Drug albendazole plus praziquantel regime
  Subjects will receive a combination of albendazole plus praziquantel, as a standard treatment for brain cysticercosis (neurocysticercosis), orally, for ten days. Albendazole will be given at 15/kg/d and praziquantel at 50/kg/d.

Primary outcome measures

• Efficacy: completely resolution or persistence only as small lesion remnants. [Time frame: Three months after treatment onset]

Secondary outcome measures (2)

• Clinical effectiveness: Seizure relapses. [Time frame: In the initial 12 months after treatment]
• Safety: Serious adverse events [Time frame: In the initial 12 months after treatment]

Eligibility criteria

Inclusion criteria

• Male or female individuals between 18 and 75 years of age, with suspected viable or degenerating intraparenchymal brain cysticercosis on neuroimaging (CT or MRI) and fulfill the diagnostic criteria for solitary cysticercus granuloma (Rajshekhar and Chandy, 1997)
• If female of child-bearing potential and men, willing to use an adequate method of contraception\*, including implants, injectables, combined oral contraceptives, effective intrauterine devices, sexual abstinence, or vasectomized partner while participating in the study.
• Patients with normal laboratory values for hemoglobin, platelet counts, total white blood cells, glucose, creatinine, bilirubin, ALT, and AST.
• Availability to grant informed consent.

Exclusion criteria

• Multiple lesion sites or more than two adjacent lesions.
• Suspected neurotuberculosis (Rajshekhar's criteria) \[66,67\]
• More than two viable brain cysts.
• Large brain cysts (> 3cm in diameter)
• Subarachnoid neurocysticercosis or intraventricular
• Untreated ocular cysticercosis
• Previous therapy with ABZ (does not include patients who received single-dose 400 mg ABZ for intestinal parasites), or PZQ in the past twelve months.
• Active pulmonary tuberculosis evidenced by a positive chest X-ray and positive sputum smears.
• Systemic disease other than NCC that may affect therapy or short-term prognosis, including but not limited to chronic renal failure, hepatic insufficiency, cardiac failure, and steroid-dependent immune diseases.
• Patients in unstable condition or with severe intracranial hypertension (ICH). Definition of severe ICH for this study would be the presence of headaches, nausea, and vomiting, and papilledema at fundoscopic examination.
• Pregnancy
• History of hypersensitivity to ABZ or PZQ
• Concurrent treatment with cimetidine, ranitidine, or theophylline.
• Chronic alcohol or drug abuse.
• Positive to Strongyloides infection
• History of reported allergy to contrast substances used in MRI.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06565507 · 211661

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗