Brain Cysticercosis
Conditions
Keywords
Cysticercosis, Cysticercosis treatment
Brief summary
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
DRUGOxfendazole 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.
DRUGOxfendazole three doses
Subjects will receive active oxfendazole, 20 mg/kg/day, orally, in three days (1, 4 and 7)
DRUGalbendazole 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.
Sponsors
Universidad Peruana Cayetano Heredia
Oxfendazole Development Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
This study is a double-blind trial in regards to dose regime of OXF. Neither the investigators nor the subjects know which dose of OXF a given subject is receiving, although subjects and clinical study staff will know whether they are receiving one of the OXF regimes or active ABZ+PZQ.
Intervention model description
The intervention administered orally will be done randomly, in three groups or arms; arms 1 and 2, receiving oxfendazole (OXF) in a single dose or oxfendazole in three-days regimen (days 1, 4 and 7), respectively; arm 3, receiving a ten days albendazole (ABZ) + praziquantel (PZQ) regimen.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. 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) 2. 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. 3. Patients with normal laboratory values for hemoglobin, platelet counts, total white blood cells, glucose, creatinine, bilirubin, ALT, and AST. 4. Availability to grant informed consent.
Exclusion criteria
1. Multiple lesion sites or more than two adjacent lesions. 2. Suspected neurotuberculosis (Rajshekhar's criteria) \[66,67\] 3. More than two viable brain cysts. 4. Large brain cysts (\> 3cm in diameter) 5. Subarachnoid neurocysticercosis or intraventricular 6. Untreated ocular cysticercosis 7. 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. 8. Active pulmonary tuberculosis evidenced by a positive chest X-ray and positive sputum smears. 9. 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. 10. 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. 11. Pregnancy 12. History of hypersensitivity to ABZ or PZQ 13. Concurrent treatment with cimetidine, ranitidine, or theophylline. 14. Chronic alcohol or drug abuse. 15. Positive to Strongyloides infection 16. History of reported allergy to contrast substances used in MRI.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy: completely resolution or persistence only as small lesion remnants. | Three months after treatment onset | Proportion of participants whose lesions completely resolved or persist only as small lesion remnants (\<20% of the original lesion size). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical effectiveness: Seizure relapses. | In the initial 12 months after treatment | The frequency of seizure relapses in individuals whose lesions resolved compared to those who had remaining viable or degenerating lesions on month 3 MRI |
| Safety: Serious adverse events | In the initial 12 months after treatment | Proportion of participants in each group who develop serious or severe adverse events, and the numbers of adverse events per group |
Contacts
CONTACTHector H Garcia, MD, PhD
CONTACTJavier A Bustos, MD, PhD
PRINCIPAL_INVESTIGATORHector H Garcia, MD, PhD
Universidad Peruana Cayetano Heredia
Outcome results
None listed