Corticosteroids to Treat Neurocysticercosis

Condition(s) targeted: Seizures; Neurocysticercosis; Cysticercosis

Intervention: Dexamethasone (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Overall contact:
Hector H. Garcia, M.D., Phone: Not Listed, Email: hgarcia@jhsph.edu

The purpose of this protocol is to determine if enhanced dosing of corticosteroids for one month with a two week taper decreases seizure frequency compared to 10 days of corticosteroids in albendazole treated patients with intraparenchymal cysticercosis without an unacceptable increase in side effects or a decrease in treatment efficacy. Much of the pathology and subsequently symptoms caused by cysticercosis are due to the host's immune response to the parasite that causes inflammation, seizures or focal neurological deficits. This leads to cyst degeneration, granuloma formation and/or calcification. The cysticidal agents, albendazole and praziquantel, initiate a similar process and until recently it was unclear if clinical benefit occurred with treatment. Earlier this year a clear benefit of treatment compared to no treatment was demonstrated. Although an overall decrease in generalized seizures was found after treatment with a standard regimen of albendazole and 6 mg dexamethasone/day for 10 days, a relative increase in seizures in the first month compared to later time periods suggested that inflammation was inadequately suppressed. Exactly what is the best way to suppress treatment-induced inflammation has not been studied and therefore is not known. The current protocol is an open label controlled study comparing the previous dexamethasone dosing of 10 days of 6 mg/day of dexamethasone with an enhanced dosing of 4 weeks of 8 mg/day with a 2 week taper. Albendazole dosing of both groups is identical. The primary end point is the number of seizures at specific time periods over the subsequent year, the number and severity of side effects and cure rates at 1 year.

Official title: Treatment of Intraparenchymal Neurocysticercosis: Effect of Increased Dosing of Corticosteroids on Seizure Frequency

Study design: Treatment

Primary outcome: Cummulative frequency of partial seizures, generalized seizures and total seizures during the period from study day 11 to study day 42, inclusive, and cummulative frequency of seizures with generalization.

Secondary outcome: Partial list, secondary outcomes, Cumulative seizures, days 43-90, 90, 360, Percentage without seizures, days 90-360, Percentage with /without viable cysts, days 180, 360, Percentage requiring more antiparasitic Rx, days 180, 360.

Detailed description: The purpose of this protocol is to determine if enhanced dosing of corticosteroids for one month with a two week taper decreases seizure frequency compared to 10 days of corticosteroids in albendazole treated patients with intraparenchymal cysticercosis without an unacceptable increase in side effects or a decrease in treatment efficacy. Much of the pathology and subsequently symptoms caused by cysticercosis are due to the host's immune response to the parasite that causes inflammation, seizures or focal neurological deficits. This leads to cyst degeneration, granuloma formation and/or calcification. The cysticidal agents, albendazole and praziquantel, initiate a similar process and until recently it was unclear if clinical benefit occurred with treatment. Earlier this year a clear benefit of treatment compared to no treatment was demonstrated. Although an overall decrease in generalized seizures was found after treatment with a standard regimen of albendazole and 6 mg dexamethasone/day for 10 days, a relative increase in seizures in the first month compared to later time periods suggested that inflammation was inadequately suppressed. Exactly what is the best way to suppress treatment-induced inflammation has not been studied and therefore is not known. The current protocol is an open label controlled study comparing the previous dexamethasone dosing of 10 days of 6 mg/day of dexamethasone with an enhanced dosing of 4 weeks of 8 mg/day with a 2 week taper. Albendazole dosing of both groups is identical. The primary end point is the number of seizures at specific time periods over the subsequent year, the number and severity of side effects and cure rates at 1 year.

Minimum age: 16 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

- INCLUSION CRITERIA:

Diagnosis of intraparencyhmal neurocysticercosis with 20 or less viable (active) cysts as determined by MRI and CAT scan.

Positive serology by EITB western blot.

Adult male or female between 16-65 years of age.

Patients with a diagnosis of epilepsy secondary to NCC and a history of one or more spontaneous seizures within the previous 6 months but not longer than 10 years.

Willingness to be hospitalized for a minimum of two weeks and longer if complications occur.

Normal laboratory values for hematocrit, platelets, WBC and glucose and normal or decreased values for creatinine.

Patients with AST or ALT values of 2. 3 times the upper limit of normal or lower can be included if the patient is otherwise healthy and there is no other evidence of liver disease.

Absence of signs of Intracranial Hypertension (ICH).

Negative fecal exam for Taenia eggs.

PPD measurement and if positive (greater than 9mm induration in the absence of other findings or immunosuppression), negative smears for TB.

Willingness to use a specified form of birth control while on study medications and for at least 1 month following albendazole therapy.

EXCLUSION CRITERIA:

Primary generalized seizures (not caused by neurocysticercosis).

Patient with ventricular NCC.

Patients with subarachnoid cysts in the Sylvian fissue or basal cisterns excepting Sylvian fissure located cysts substantially surrounded by brain parenchyma by MRI.

Any vesicular lesion greater than 2. 5 cm of diameter.

Previous therapy with albendazole in the past two years excepting patients treated with up to 1200mg albendazole two months or greater prior to evaluation who demonstrate continued viability of cysts.

Intracranial hypertension defined radiologically by CT or MRI.

A history of generalized status epilepticus.

Focal permanent neurological deficits.

Unstable vital signs - Consistently abnormal vital signs: body temperature, pulse (heart

rate), respiratory rate (breathing), and blood pressure.

Cysts in critical regions including brainstem or eye cysts.

Pulmonary tuberculosis.

History of TB in the patient or history of untreated TB in close relative with whom the patient was living.

Chest X-ray suggestive of past TB.

Pre-existing diagnosis of diabetes.

Systemic conditions 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.

Ill and not likely to survive a year from any cause.

Pregnancy during albendazole treatment.

Unwilling or unable to undergo MRI examination; has ferromagnetic objects.

Unwilling or unable to provide a CT scan initially or an MRI at 6 months, or CT scan at end of therapy or delayed CT scan if pregnant.

History of hypersensitivity to albednazole.

Breast feeding during treatment.

Hypertension at rest.

The patient is currently on corticosteroids, received corticosteroids within the past 2 weeks, or has had a course of corticosteroids within the past 6 months lasting 9 days or more.

Other CNS processes that may be confused with changes in CNS function due to cysticercosis.

Pregnancy as demonstrated by a positive (urine or serum) bHCG.

Clinical AIDS.

Positive HIV and positive PPD (greater than 5 mm).

Hector H. Garcia, M.D., Phone: Not Listed, Email: hgarcia@jhsph.edu

Universidad Peruana Cayetano Heredia, Lima, Peru; Recruiting
Hector Garcia, M.D., Sub-Investigator

Instituto Nacional de Ciencias Neurologicas, Lima, Peru; Recruiting

Related publications:

[No authors listed] Relationship between epilepsy and tropical diseases. Commission on Tropical Diseases of the International League Against Epilepsy. Epilepsia. 1994 Jan-Feb;35(1):89-93. Review. No abstract available.

Garcia HH, Gilman R, Martinez M, Tsang VC, Pilcher JB, Herrera G, Diaz F, Alvarado M, Miranda E. Cysticercosis as a major cause of epilepsy in Peru. The Cysticercosis Working Group in Peru (CWG) Lancet. 1993 Jan 23;341(8839):197-200.

Medina MT, Rosas E, Rubio-Donnadieu F, Sotelo J. Neurocysticercosis as the main cause of late-onset epilepsy in Mexico. Arch Intern Med. 1990 Feb;150(2):325-7.

Starting date: March 2005
Last updated: October 4, 2008