Pilot Trial of Valproate as Adjunctive Treatment for Toxoplasma Gondii Infection in Early Course Schizophrenia

NCT ID: NCT02011750

Last Updated: 2018-02-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 109 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-01
• Study Completion Date: 2017-12-31

Brief Summary

This is an exploratory study in Egypt that will combine a treatment trial among early course schizophrenia (ECSZ) patients with key analyses suggested by rodent studies. Specifically, the study will test the provocative results from animal studies indicating an impact of Toxoplasma Gondii (TOX) exposure on novelty seeking. The study will also test whether exposure to TOX is associated with other cognitive and behavioral changes, as well as changes in overall social function. We will also explore the relative efficacy of Sodium Valproate (Depakote, DEP) in improving clinical and overall social function among TOX exposed and unexposed patients.

Hypotheses

1. At baseline, TOX exposure is associated with increased novelty seeking, clinical severity, and impaired cognitive and overall social function in patients with SZ.

2. Adjunctive DEP treatment improves clinical symptoms, cognitive and social function in SZ, particularly among TOX exposed SZ patients.

3. Exploratory hypothesis: adjunctive DEP reduces serological indices of TOX infection (VIP and TH levels).

Conditions

Toxoplasmosis; Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Sodium Valproate treatment

Sodium Valproate treatment:During the entry period, all patients will have a placebo run-in for two weeks after which they will be evaluated for the outcome variables and then randomized to either Sodium Valproate (Depakote, DEP) or placebo (PLA) group in a 1:1 proportion. For the Sodium Valproate treatment grou, this will be followed by a two week period to adjust the dose of DEP and attain therapeutic levels (50-100 µg/mL). Then DEP treatment will continue for 16 more weeks, after which DEP will be discontinued. Subject will be followed up for four weeks post-DEP discontinuation to monitor delayed adverse side effects.

Group Type: EXPERIMENTAL

Sodium Valproate treatment

Intervention Type: DRUG

Sodium Valproate treatment:During the entry period, all patients will have a placebo run-in for two weeks after which they will be evaluated for the outcome variables and then randomized to either Sodium Valproate (Depakote, DEP) or placebo (PLA) group in a 1:1 proportion. For the Sodium Valproate treatment group, this will be followed by a two week period to adjust the dose of DEP and attain therapeutic levels (50-100 µg/mL). Then DEP treatment will continue for 16 more weeks, after which DEP will be discontinued. Subject will be followed up for four weeks post-DEP discontinuation to monitor delayed adverse side effects.

Placebo

Intervention Type: DRUG

Placebo: During the entry period, all patients will have a placebo run-in for two weeks after which they will be evaluated for the outcome variables and then randomized to either the experimental Sodium Valproate (Depakote, or DEP) or placebo (PLA) group in a 1:1 proportion. For the PLA group, this will be followed by a two week period of placebo during which members of the experimental Sodium Valproate (Depakote/DEP) will have DEP dose adjusted to attain therapeutic levels (50-100 µg/mL). Then PLA treatment will continue for 16 more weeks. Subjects will be followed up for four weeks post PLA-discontinuation to monitor for delayed adverse side effects.

Placebo

Placebo Comparator: During the entry period, all patients will have a placebo run-in for two weeks after which they will be evaluated for the outcome variables and then randomized to either the experimental Sodium Valproate (Depakote, or DEP) or placebo (PLA) group in a 1:1 proportion. For the PLA group, this will be followed by a two week period of placebo during which members of the experimental Sodium Valproate (Depakote/DEP) will have DEP dose adjusted to attain therapeutic levels (50-100 µg/mL). Then PLA treatment will continue for 16 more weeks. Subjects will be followed up for four weeks post PLA-discontinuation to monitor for delayed adverse side effects.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo: During the entry period, all patients will have a placebo run-in for two weeks after which they will be evaluated for the outcome variables and then randomized to either the experimental Sodium Valproate (Depakote, or DEP) or placebo (PLA) group in a 1:1 proportion. For the PLA group, this will be followed by a two week period of placebo during which members of the experimental Sodium Valproate (Depakote/DEP) will have DEP dose adjusted to attain therapeutic levels (50-100 µg/mL). Then PLA treatment will continue for 16 more weeks. Subjects will be followed up for four weeks post PLA-discontinuation to monitor for delayed adverse side effects.

Interventions

Sodium Valproate treatment

Sodium Valproate treatment:During the entry period, all patients will have a placebo run-in for two weeks after which they will be evaluated for the outcome variables and then randomized to either Sodium Valproate (Depakote, DEP) or placebo (PLA) group in a 1:1 proportion. For the Sodium Valproate treatment group, this will be followed by a two week period to adjust the dose of DEP and attain therapeutic levels (50-100 µg/mL). Then DEP treatment will continue for 16 more weeks, after which DEP will be discontinued. Subject will be followed up for four weeks post-DEP discontinuation to monitor delayed adverse side effects.

Intervention Type: DRUG

Placebo

Placebo: During the entry period, all patients will have a placebo run-in for two weeks after which they will be evaluated for the outcome variables and then randomized to either the experimental Sodium Valproate (Depakote, or DEP) or placebo (PLA) group in a 1:1 proportion. For the PLA group, this will be followed by a two week period of placebo during which members of the experimental Sodium Valproate (Depakote/DEP) will have DEP dose adjusted to attain therapeutic levels (50-100 µg/mL). Then PLA treatment will continue for 16 more weeks. Subjects will be followed up for four weeks post PLA-discontinuation to monitor for delayed adverse side effects.

Intervention Type: DRUG

Other Intervention Names

Depakote

Eligibility Criteria

Inclusion Criteria

• Written informed consent
• Adult men or women (ages 18-50 years)
• Schizophrenia / schizoaffective disorder (DSM IV)
• Duration of illness < 5 years (since onset of psychosis)
• On a stable dose of an antipsychotic for at least a month
• Scores 4 or more on at least one item of the Positive and Negative Syndrome Scale.

Exclusion Criteria

• Substance abuse in the past month/dependence past 6 months
• History of / or current medical/neurological illnesses e.g. mental retardation (DSM-IV) or epilepsy;
• Medical conditions that are judged by the consulting internist and research staff to be unstable
• Pregnant or breast-feeding women
• Known allergy or serious adverse event to DEP, Received Chlorpromazine, Trimethoprim or DEP for up to 6 months prior to study entry.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mansoura University

OTHER

Sponsor Role: collaborator

Stanley Medical Research Institute

OTHER

Sponsor Role: collaborator

University of Pittsburgh

OTHER

Sponsor Role: lead

Responsible Party

Hader Mansour, MD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hader Mansour, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

Mansoura University Hospital

Al Mansurah, , Egypt

Countries

Egypt

Other Identifiers

PRO12020320

Identifier Type: -

Identifier Source: org_study_id