Double-Blind Trial of a Probiotic Supplement to Reduce the Symptoms of Schizophrenia

Study Overview
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Brief Summary
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The investigators intend to explore the hypothesis that symptoms of schizophrenia may be reduced by the administration of a probiotic supplement when used in addition to standard antipsychotic medications.

Detailed Description
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The primary aim of the current study is: To evaluate the safety and efficacy of a supplemental probiotic therapy, containing the microorganisms Lactobacillus rhamnosus GG and Bifidobacterium lanimalis subsp. lactis (BB12), for individuals with schizophrenia who have residual psychotic symptoms of at least moderate severity. Secondary aims of the study are: To assess the effect of probiotic treatment on patients' gastrointestinal functioning To study the effect of probiotic treatment in lowering the levels of antibodies to casein and gliadin. To investigate the association between the efficacy of probiotic therapy and initial levels of antibodies to gliadin and casein.

Official Title
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A Double-Blind Placebo-Controlled Trial of a Probiotic Supplement to Reduce the Symptoms of Schizophrenia

Conditions
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Schizophrenia, Schizoaffective Disorder

Intervention / Treatment
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* Dietary Supplement: Probiotic Supplement
* Dietary Supplement: Identical-appearing Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-65. Capacity for written informed consent. Primary Axis I diagnosis (DSM-IV) of schizophrenia, any type, OR schizoaffective disorder (APA, 1994). Currently an outpatient at the time of enrollment. Residual psychotic symptoms which are at least moderately severe as evidenced by one or more PANSS positive symptom scores, and/or PANSS negative symptom scores of 4 or more; OR a total PANSS score of 50 or more, containing at least three positive or negative items with scores of 3 or more at screening. Conformance to PORT Treatment Recommendation re Maintenance Antipsychotic Medication Dose (Buchanan et al., 2010). Receiving antipsychotic medication for at least 8 weeks prior to starting the study with no medication changes within the previous 21 days. Proficient in the English language. Exclusion Criteria: Diagnosis of mental retardation. Any clinically significant or unstable medical disorder as determined by the investigators, including congestive heart failure, abnormal liver function or disease, renal failure, acute pancreatitis, any diagnosis of cancer undergoing active treatment, HIV infection or other immunodeficiency condition. History of IV drug use. Primary diagnosis of substance abuse or dependence according to DSM-IV criteria within the last three months. Participated in any investigational drug trial in the past 30 days. Pregnant or planning to become pregnant during the study period. Receipt of antibiotic medication within the previous 14 days (as anaerobic organisms residing in the gastrointestinal tract may be minimally affected by antibiotics). Documented celiac disease (as such persons should be on a gluten-free diet as this is the standard care). Of note, the investigators are not limiting the study to individuals with elevated levels of gliadin or casein antibodies as the investigators intend to look at these levels as a predictor of response.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Probiotic Supplement<br>Probiotic supplement 1 tablet by mouth daily for 14 weeks after 2 week placebo run-in | Dietary Supplement: Probiotic Supplement<br>* Probiotic Supplement 1 tablet by mouth daily<br>|
| Placebo Comparator: Identical-appearing Placebo<br>Identical appearing placebo 1 tablet by mouth daily for 14 weeks after 2 week placebo run-in | Dietary Supplement: Identical-appearing Placebo<br>* Probiotic identical placebo 1 tablet by mouth daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Positive and Negative Syndrome Scale (PANSS) Score From the Start to the End of the Double-blind Treatment Phase (Week 0 to Week 14) | The Positive and Negative Syndrome Scale (PANSS) measures psychiatric symptomatology, especially related to psychosis. The complete PANSS contains ratings for 30 symptoms, including 7 positive symptoms, 7 negative symptoms, and 16 general psychiatric symptoms. The severity of each symptom is rated on a scale ranging from 1 (minimal) to 7 (extreme); higher scores indicate increased symptomatology. Total PANSS scores include scores from all categories and range from 30 to 210 units on a scale. | 14 weeks (week 0 to week 14) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gastrointestinal Functioning From the Beginning to the End of the Double-blind Treatment Phase Weeks 0-14 | Self report rating of difficulty moving bowels on a 4 point scale from no difficulty to severe difficulty | 14 weeks (weeks 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 & 14) | 
| Measurement of Gliadin and Casein Antibody Levels |  | 16 weeks (baseline prior to placebo run in to week 14) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Schizoaffective, Probiotic supplements, Gliadin, Casein