Schizophrenia, Schizoaffective Disorder
Conditions
Keywords
Schizophrenia, Schizoaffective, Probiotic supplements, Gliadin, Casein
Brief summary
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
The primary aim of the current study is: 1. 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: 2. To assess the effect of probiotic treatment on patients' gastrointestinal functioning 3. To study the effect of probiotic treatment in lowering the levels of antibodies to casein and gliadin. 4. To investigate the association between the efficacy of probiotic therapy and initial levels of antibodies to gliadin and casein.
Interventions
DIETARY_SUPPLEMENTProbiotic Supplement
Probiotic Supplement 1 tablet by mouth daily
DIETARY_SUPPLEMENTIdentical-appearing Placebo
Probiotic identical placebo 1 tablet by mouth daily
Sponsors
Stanley Medical Research Institute
Sheppard Pratt Health System
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 14 weeks (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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Gastrointestinal Functioning From the Beginning to the End of the Double-blind Treatment Phase Weeks 0-14 | 14 weeks (weeks 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 & 14) | Self report rating of difficulty moving bowels on a 4 point scale from no difficulty to severe difficulty |
| Measurement of Gliadin and Casein Antibody Levels | 16 weeks (baseline prior to placebo run in to week 14) | — |
Countries
United States
Participant flow
Recruitment details
We enrolled n=65 participants drawn from rehabilitation and treatment programs in Central Maryland. Dates of recruitment 11/2010-01/2012.
Pre-assignment details
We used a 2 week placebo run in for all participants prior to randomization. This placebo run in was followed by the 14 week double-blind treatment phase.
Participants by arm
| Arm | Count |
|---|---|
| Probiotic Supplement Probiotic supplement 1 tablet by mouth daily for 14 weeks | 33 |
| Identical-appearing Placebo Identical appearing placebo 1 tablet by mouth daily for 14 weeks | 32 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 0 | 3 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Identical-appearing Placebo | Probiotic Supplement | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants | 32 Participants | 64 Participants |
| Age, Continuous | 48.1 years STANDARD_DEVIATION 9.4 | 44.4 years STANDARD_DEVIATION 11 | 46.2 years STANDARD_DEVIATION 10.4 |
| Region of Enrollment United States | 32 participants | 33 participants | 65 participants |
| Sex: Female, Male Female | 13 Participants | 10 Participants | 23 Participants |
| Sex: Female, Male Male | 19 Participants | 23 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 19 / 33 | 21 / 32 |
| serious Total, serious adverse events | 2 / 33 | 1 / 32 |
Outcome results
Primary
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.
Time frame: 14 weeks (week 0 to week 14)
Population: Week 0 data is based on the number of participants in the probiotic supplement group (n=33) and the placebo group (n=32) who began the treatment phase. Week 14 data is based on the number of participants in the probiotics supplement group (n=31) and the placebo group (n=27) who completed the treatment phase.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Probiotic Supplement | 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) | Wk 0 (Begin Treatment) PANSS Total Score, n=33,32 | 67.55 units on a scale | Standard Deviation 11.64 |
| Probiotic Supplement | 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) | Wk 14 (End Treatment) PANSS Total Score, n=31,27 | 67.42 units on a scale | Standard Deviation 11.66 |
| Identical-appearing Placebo | 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) | Wk 0 (Begin Treatment) PANSS Total Score, n=33,32 | 69.56 units on a scale | Standard Deviation 11.73 |
| Identical-appearing Placebo | 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) | Wk 14 (End Treatment) PANSS Total Score, n=31,27 | 67.69 units on a scale | Standard Deviation 11.86 |
Secondary
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
Time frame: 14 weeks (weeks 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 & 14)
Secondary
Measurement of Gliadin and Casein Antibody Levels
Time frame: 16 weeks (baseline prior to placebo run in to week 14)