Neurocysticercosis: Combined Treatment With Praziquantel (PZQ) and Albendazole (ABZ)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Universidad Peruana Cayetano Heredia
ClinicalTrials.gov Identifier:
NCT00441285
First received: February 27, 2007
Last updated: July 3, 2013
Last verified: July 2013
  Purpose

The purpose of this study is to determine if combination drug therapy of praziquantel and albendazole is safe and effective to cure neurocysticercosis.


Condition Intervention Phase
Neurocysticercosis
Epilepsy
Drug: Praziquantel
Drug: Albendazole
Drug: ABZ Placebo
Drug: PZQ Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Antiparasitic Therapy for Neurocysticercosis: Phase II/III Study on Safety and Efficacy of Combined Treatment With Praziquantel and Albendazole

Resource links provided by NLM:


Further study details as provided by Universidad Peruana Cayetano Heredia:

Primary Outcome Measures:
  • PK Substudy - Area Under the Curve of Albendazole in Treatment in Day 1 [ Time Frame: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 12 hours post dose on Treatment day 1 ] [ Designated as safety issue: No ]
    - To evaluate kinetic disposition of Albendazole we calculated the Area under the curve of the active metabolite of Albendazole (Albendazole Sulphoxide) with Praziquantel or Placebo (of Praziquantel).

  • PK Substudy - Area Under the Curve of Albendazole in Treatment Days 10 and 11 [ Time Frame: 0.5, 1, 1.5, 2, 3, 4, 8, 10, 12, 24 and 36 hours post dose on Treatment days 10-11 ] [ Designated as safety issue: No ]
    - To evaluate kinetic disposition of Albendazole we calculated the Area under the curve of the active metabolite of Albendazole (Albendazole Sulphoxide) with Praziquantel or Placebo (of Praziquantel).

  • PK Substudy - Maximum Concentration of Albendazole [ Time Frame: Treatment day 1 and Treatment days 10-11 ] [ Designated as safety issue: Yes ]
    Highest serum level of Albendazole measured from all level assessments in the curve.

  • Phase III Trial - Proportion of Patients Without Remaining Live Cysts [ Time Frame: Day 180 ] [ Designated as safety issue: No ]
    Proportion of patients whose 6 month MR does not show viable parasites anymore


Secondary Outcome Measures:
  • PK Substudy - Area Under the Curve of Praziquantel by Antiepileptic Drug in Treatment Day 1 [ Time Frame: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 12 hours post dose in treatment day 1 ] [ Designated as safety issue: No ]
    - To evaluate the kinetic disposition of Praziquantel by antiepileptic drug after the last praziquantel dose, we calculated the Area Under the Curve of Praziquantel with Carbamazepine or Phenytoin

  • PK Substudy - Area Under the Curve of Praziquantel by Antiepileptic Drug in Treatment Days 10 and 11 [ Time Frame: 0.5, 1, 1.5, 2, 3, 4, 8, 10, 12, 24 and 36 hours post dose on treatment days 10-11 ] [ Designated as safety issue: No ]
    - To evaluate the kinetic disposition of Praziquantel by antiepileptic drug after the last praziquantel dose, we calculated the Area Under the Curve of Praziquantel with Carbamazepine or Phenytoin

  • PK Substudy - Safety of Combined Albendazole Plus Praziquantel Therapy [ Time Frame: 90 days post tx ] [ Designated as safety issue: Yes ]
    - Describe if some Serious Adverse Event was associated to combined Albendazole plus Praziquantel therapy.

  • Phase III Trial - Proportion of Cysts Which Resolved [ Time Frame: Day 180 ] [ Designated as safety issue: No ]
    Proportion of Viable Brain Parasites which Are not Alive Anymore at 6 Months MRI

  • Phase III Trial - Seizure Frequency [ Time Frame: Day 1 - 540 ] [ Designated as safety issue: No ]
    Seizure frequency by treatment group


Enrollment: 156
Study Start Date: January 2010
Estimated Study Completion Date: September 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: I. ABZ + ABZ Placebo + PZQ
Albendazole 15 mg / kg / d (until 800 mg / d) + Placebo of Albendazole ( 7.5 mg / Kg / d )+ Praziquantel 50 mg / kg / d (until 3600 mg / d)
Drug: Praziquantel
- Praziquantel 50 mg / kg / d (up to 3600 mg / d ) for 10 days.
Other Name: PZQ
Drug: Albendazole
  • Albendazole 15 mg / kg / d ( up to 800 mg /d ) in Arm I for 10 days.
  • Albendazole at an increased dose, 22.5 mg / kg / d (up to 1200 mg / d ), in Arm II for 10 days.
Other Name: ABZ
Drug: ABZ Placebo
- Placebo (of Albendazole ) 7.5 mg / kg / d in Arm I and II for 10 days.
Other Name: Placebo of Albendazole
Active Comparator: II.- ABZ + ABZ Placebo + PZQ Placebo
Albendazole 15 mg / kg / d ( until 800 mg / d ) + Placebo of Albendazole ( 7.5 mg / Kg / d ) + Placebo of Praziquantel ( 50 mg / kg / d )
Drug: Albendazole
  • Albendazole 15 mg / kg / d ( up to 800 mg /d ) in Arm I for 10 days.
  • Albendazole at an increased dose, 22.5 mg / kg / d (up to 1200 mg / d ), in Arm II for 10 days.
Other Name: ABZ
Drug: ABZ Placebo
- Placebo (of Albendazole ) 7.5 mg / kg / d in Arm I and II for 10 days.
Other Name: Placebo of Albendazole
Drug: PZQ Placebo
- Placebo (of Praziquantel) 50 mg / kg / d in Arm II and III for 10 days.
Other Name: Placebo of PZQ
Active Comparator: III .- Albendazole + PZQ Placebo

Albendazole 22.5 mg / kg / d (until 1200 mg / d) + Placebo of Praziquantel ( 50 mg / kg / d )

This arm was not used in the first substudy ( initial part and guide to the design of the parent study ) however it will be used henceforward.

Drug: Albendazole
  • Albendazole 15 mg / kg / d ( up to 800 mg /d ) in Arm I for 10 days.
  • Albendazole at an increased dose, 22.5 mg / kg / d (up to 1200 mg / d ), in Arm II for 10 days.
Other Name: ABZ
Drug: PZQ Placebo
- Placebo (of Praziquantel) 50 mg / kg / d in Arm II and III for 10 days.
Other Name: Placebo of PZQ

Detailed Description:

Neurocysticercosis is the single major cause of acquired or late-onset epilepsy in the world, and a common diagnosis in immigrant populations in the United States and other industrialized countries. An estimated 50 million humans are affected by Neurocysticercosis. The disease occurs when a parasite called Taenia solium, or the pig tapeworm, infects the brain, forming cysts. Neurocysticercosis is generally treated with 1 of 2 drugs, praziquantel or albendazole. However, current treatment with either of these drugs alone is not totally effective.

The goal of this trial is to determine if combination drug therapy of praziquantel and albendazole is safe and more effective to cure Neurocysticercosis than either drug administered alone. This trial will consist of two sub-studies and a parent study.

In the first substudy which was performed and completed as the initial part and guide to the design of the parent study, a series of 32 patients with viable cystic intraparenchymal Neurocysticercosis were treated with either albendazole ( 15 mg / kg /d ) + praziquantel ( 50 mg / kg/ d ) or albendazole+Placebo in a double blind randomized study. Half of patients in each group had their seizure disorder treated with phenytoin and the other half with carbamazepine (not assigned by the study). The study was designed and powered for pharmacokinetic evaluation and exploratory safety so comparative cysticidal efficacy has not yet been analyzed. There were no safety concerns. Pharmacokinetics of ABZ and PZQ were obtained and described.

In the parent study, a total of 240 participants ( including the 32 participants from the first substudy ) will be randomly chosen to receive albendazole + praziquantel, albendazole + placebo or albendazole at an increased dose + placebo for 10 days. These groups will also receive other standard medications to manage the disease including appropriate anti-epileptic drug therapy. Participants will stay in the hospital for at least 2 weeks after treatment begins, which includes 5 days after the end of anti-parasitic treatment. After discharge from the hospital, follow-up visits will be on days 21 and 30 after treatment begins, then monthly until day 90, and finally every 3 months until completing 18 months. Brain images will be taken at 6 and 12 months after treatment begins. For participants, duration of the trial is 1 year and a half.

  Eligibility

Ages Eligible for Study:   16 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

For parent study:

Inclusion Criteria:

  • Male or female individuals between 16 to 65 years of age, with a diagnosis of Neurocysticercosis and 20 or less viable cysts.
  • Patients with a diagnosis of epilepsy secondary to Neurocysticercosis and a history of one or more spontaneous seizures within the previous year but not longer than 10 years.
  • Willingness to complete a minimum of two weeks of hospitalization.
  • If female of child bearing potential, negative urine pregnancy testing and willingness to use an adequate method of contraception while on study medications and for at least 3 months following Albendazole therapy.
  • Normal laboratory values for hematocrit, platelets, white blood cells and glucose and normal or decreased values for Alanine transaminase, Aspartate transaminase and creatinine.
  • Negative PPD measurement and if positive ( > 9mm induration in the absence of other findings or immunosuppression ) , negative smears for TB.
  • Negative fecal exam for Taenia eggs or Strongyloides larvae.

Exclusion Criteria:

  • Primary generalized seizures ( e.g., not caused by Neurocysticercosis )
  • A history of generalized epileptic status .
  • A type of Neurocysticercosis which can expose the patient to increased risk during the study.
  • Patients with persistent or progressive symptomatic intracranial hypertension or intracranial hypertension.
  • Previous therapy with Albendazole or Praziquantel in the previous year.
  • Pulmonary tuberculosis, or symptoms compatible with tuberculosis not otherwise explained.
  • Active hepatitis
  • Systemic disease that may affect short term prognosis.
  • Patients in unstable condition ( consistently abnormal vital signs: body temperature, heart rate, respiratory rate, and blood pressure )
  • Pregnancy during antiparasitic treatment
  • History of hypersensitivity to Albendazole or Praziquantel
  • Concurrent treatment with Cimetidine or Theophylline
  • Chronic alcohol or drug abuse
  • Unwilling or unable to provide a Computed tomography initially or an Magnetic resonance imaging at 6 months ( as patients with ferromagnetic implants ) , Computed tomography at the end of therapy.
  • Unwillingness of subject or legal representative to give written informed consent.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00441285

Locations
Peru
Universidad Peruana Cayetano Heredia
Lima, Peru
Instituto Nacional de Ciencias Neurologicas
Lima, Peru
Hospital Nacional Cayetano Heredia
Lima, Peru, Lima 31
Hospital Nacional Edgardo Rebagliati
Lima, Peru, Lima 11
Hospital Nacional Guillermo Almenara
Lima, Peru, Lima 5
Sponsors and Collaborators
Universidad Peruana Cayetano Heredia
Investigators
Principal Investigator: Hector H. Garcia, MD Universidad Peruana Cayetano Heredia
Principal Investigator: E. Javier Pretell, MD Hospital Alberto
Principal Investigator: Javier A. Bustos, MD Universidad Peruana Cayetano Heredia
  More Information

Publications:
Responsible Party: Universidad Peruana Cayetano Heredia
ClinicalTrials.gov Identifier: NCT00441285     History of Changes
Other Study ID Numbers: R01NS054805, R01NS054805
Study First Received: February 27, 2007
Results First Received: January 28, 2010
Last Updated: July 3, 2013
Health Authority: United States: Federal Government

Keywords provided by Universidad Peruana Cayetano Heredia:
neurocysticercosis
NCC
praziquantel
PZQ
albendazole
ABZ
parasite
pig tapeworm
Taenia solium
epilepsy
late-onset epilepsy
acquired epilepsy

Additional relevant MeSH terms:
Epilepsy
Neurocysticercosis
Cysticercosis
Taeniasis
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Central Nervous System Helminthiasis
Central Nervous System Parasitic Infections
Parasitic Diseases
Cestode Infections
Helminthiasis
Central Nervous System Infections
Albendazole
Praziquantel
Anthelmintics
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Anticestodal Agents
Antiplatyhelmintic Agents
Antiprotozoal Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 16, 2014