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

This study is enrolling participants by invitation only.
Sponsor:
Collaborators:
Mansoura University
Stanley Medical Research Institute
Information provided by (Responsible Party):
Hader Mansour, MD, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT02011750
First received: June 21, 2013
Last updated: December 9, 2013
Last verified: December 2013
  Purpose

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).

Condition Intervention Phase
Toxoplasmosis
Schizophrenia
Drug: Sodium Valproate treatment
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pilot Trial of Valproate as Adjunctive Treatment for Toxoplasma Gondii

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • Clinical Severity [ Time Frame: Clinical severity will be assessed during week 20 of the study. ] [ Designated as safety issue: No ]
    Clinical Severity will be measured by the Positive and Negative Syndrome Scale (PANSS),a 7 point rating scale for 30 psychopathological items based on interviews or reports.

  • Cognitive Domains assessed via the Arabic version of the Penn CNB [ Time Frame: Cognitive domains wil be measured in week 16 of the study ] [ Designated as safety issue: No ]
    Cognitive domains will be assessed using the Arabic version of the Penn Computerized Neuropsychological Battery (CNB), which includes cognitive measures that distinguish SZ cases and relatives from controls. Accuracy and response time are recorded.

  • Social Function assessed via the Quality of Life Scale [ Time Frame: Social functioing will be assessed during week during week 16. ] [ Designated as safety issue: No ]
    Overall Social function will be measured by the Quality of Life Scale, which measures interpersonal, social and occupational functioning.

  • Cognitive domains assessed via Trails Making Test [ Time Frame: Cognitive domains will be assessed in week 16 of the study ] [ Designated as safety issue: No ]
    Cognitive domains will be assessed using the Trails Making Test, a neuropsychological test of attention and task switching.

  • Social Function -assessed via the GAF scale [ Time Frame: Social functioning will be assessed during week 16 ] [ Designated as safety issue: No ]
    Social functioning will be assessed using the Global Assessment of Functioning (GAF), a global measure of function and symptom severity.

  • Social Functioning assessed via the Short Form [ Time Frame: Social functioning will be assessed during week 16 ] [ Designated as safety issue: No ]
    Social functioning will be assessed via the Short Form, a multi-item scale that consists of 8 scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight.


Secondary Outcome Measures:
  • Side effects [ Time Frame: Side effects will be measured during week 20 of the study. ] [ Designated as safety issue: Yes ]
    Participants will be monitored for adverse reactions to study medication through week 20.


Estimated Enrollment: 100
Study Start Date: March 2013
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: 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.
Other Name: Depakote
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.
Placebo Comparator: 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.
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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT02011750

Locations
Egypt
Mansoura University Hospital
Mansoura, Egypt
Sponsors and Collaborators
University of Pittsburgh
Mansoura University
Stanley Medical Research Institute
Investigators
Principal Investigator: Hader Mansour, MD University of Pittsburgh
  More Information

No publications provided

Responsible Party: Hader Mansour, MD, Professor, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT02011750     History of Changes
Other Study ID Numbers: PRO12020320
Study First Received: June 21, 2013
Last Updated: December 9, 2013
Health Authority: United States: Institutional Review Board
Egypt: Institutional Review Board

Keywords provided by University of Pittsburgh:
schizophrenia
toxoplasmosis

Additional relevant MeSH terms:
Schizophrenia
Toxoplasmosis
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Coccidiosis
Protozoan Infections
Parasitic Diseases
Valproic Acid
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs

ClinicalTrials.gov processed this record on August 20, 2014