Mania (Neurotic)
Conditions
Keywords
Probiotic, bipolar disorder, schizoaffective disorder, mania
Brief summary
This will be a 24-week, randomized, double-blind, placebo-controlled trial of adjunctive probiotic therapy in 66 persons hospitalized with a manic or mixed episode. The active study compound will consist of capsules containing approximately 10\^9 colony forming units of the probiotic organisms, Lactobacillus GG and Bifidobacteria lactis strain Bb12. The dose has been selected because it has been used safely in other probiotic trials, was well-tolerated by the participants in two previous trials of individuals with schizophrenia or mania, and was utilized in the original trial on which this replication is based. This dose is higher than that available in most commercially-sold health food supplements. Following hospital discharge, participants will be randomized to receive adjunctive probiotic or placebo for a 24 week period. It is anticipated that of the 66 participants randomized, \ 50 (75%) will complete the full 24 weeks of the study. The primary outcome is relapse, defined as re-hospitalization (e.g., admission to an inpatient unit) for psychiatric symptoms following a previous hospital discharge by at least 2 weeks. The occurrence of new mood episodes, the severity of psychiatric symptoms, and any changes in cognitive test scores over the course of the study will also be evaluated. Changes in the levels of inflammatory markers as well as changes in gut microbiota will be evaluated at three time intervals over the course of the study.
Detailed description
Primary Aim 1. To determine if adjunctive probiotic administration can reduce relapse for participants first hospitalized for mania. Hypothesis: Participants receiving adjunctive probiotic microorganisms vs. adjunctive placebo will have a lower rate of relapse as defined by a re-hospitalization (e.g., admission to an inpatient unit) during the 24 week study period. Secondary Outcomes. The number of new mood episodes, the severity of psychiatric symptoms, and changes in cognitive scores over the 24 week study period will be evaluated. Exploratory Aim 1. To study the effect of probiotic therapy in lowering the levels of inflammatory markers following an acute episode of mania. Hypothesis: Participants receiving adjunctive probiotic microorganisms vs. adjunctive placebo will have reduced levels of antibodies to casein, gliadin, and the NMDA receptor, and reduced levels of C-Reactive protein and the cytokine TNF alpha following 24 weeks of probiotic therapy. Exploratory Aim 2. To evaluate changes in the gut microbiota following probiotic administration. Hypothesis: Probiotic administration will enrich the gut microbiota of participants with the given microorganisms and these changes may correlate to changes in the peripheral inflammatory markers being measured.
Interventions
COMBINATION_PRODUCTProbio-Tec BG-VCap-6.5
The product under investigation is a probiotic containing two microorganisms (Lactobacillus rhamnosus, LGG® and Bifidobacterium animalis subsp. lactis, BB-12®, referred to as LGG® and BB-12®, respectively) and is offered commercially as Probio-Tec BG-VCap-6.5. This composition is formulated to contain a minimum of 1 billion (1.0 x 10\^9) CFU (Colony Forming Units) per dose (capsule), including equal numbers of the two strains; i.e. 0.5 x 10\^9 CFU of each of LGG® and BB-12® at the time of manufacture. The product will be administered orally.
OTHERPlacebo
This placebo is made almost identically to the Probio-Tec but without active microorganisms.
Sponsors
University of Texas Southwestern Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Capacity for written informed consent * Currently (or within the last 3 weeks) admitted to inpatient hospital for symptoms of mania. * Primary Axis I diagnosis (DSM-5) at time of admission of bipolar I (single manic episode, most recent episode manic, or most recent episode mixed) OR schizoaffective disorder, bipolar type (manic or mixed state). * Proficient in the English language. * Available to attend follow-up visits.
Exclusion criteria
* Substance- or medically-induced symptoms of mania at time of assessment. * HIV infection or other immunodeficiency condition (such as receiving cancer chemotherapy). * A serious medical condition that affects brain or cognitive functioning (e.g., epilepsy, serious head injury, concussion involving loss of consciousness, brain tumor, or other neurological disorder). Note that Hepatitis-C is not an exclusion criterion unless the participant has an acute infection. * Poorly controlled comorbid medical condition. * Major surgery in the last year. * History of weight loss surgery. * Diagnosis of Intellectual Disability or history of severe learning disorder. * Diagnosis of alcohol or substance use disorder (moderate/severe) according to DSM-5 criteria within the last 3 months, or has a positive drug toxicity screen proximate to the time of recruitment. * History of IV drug use. * Participated in any investigational drug trial in the past 30 days. * Abnormal electrolyte levels. * AST and ALT \> 3 times upper limit of normal. * Pregnant, breastfeeding, or planning to become pregnant during the study period. * Documented celiac disease (as such persons should be on a gluten-free diet as this is the standard care). Of note, we are not limiting the study to individuals with elevated levels of gliadin or casein antibodies as we intend to look at these levels as a predictor of response.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Relapse | 24 weeks | 'Relapse' is defined as re-hospitalization (e.g., admission to an inpatient unit) for psychiatric symptoms following a previous hospital discharge by at least 2 weeks. The rate of relapse was calculated by dividing the number of re-hospitalizations per group (i.e., Placebo, Probiotic) by the number of participants per group so the unit is re-hospitalizations/participant. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants will receive capsules containing placebo for 24-weeks. | 36 |
| Probiotic-Probio-Tec BG-VCap-6.5 Participants will receive capsules containing approximately 10\^9 colony forming units of the probiotic organisms, Lactobacillus GG and Bifidobacteria lactis strain Bb12 for 24-weeks. | 31 |
| Total | 67 |
Baseline characteristics
| Characteristic | Placebo | Probiotic-Probio-Tec BG-VCap-6.5 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 35 Participants | 30 Participants | 65 Participants |
| Age, Continuous | 33.97 Years STANDARD_DEVIATION 17.08 | 32.29 Years STANDARD_DEVIATION 10.18 | 33.19 Years STANDARD_DEVIATION 12.27 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 5 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants | 26 Participants | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 12 Participants | 20 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 25 Participants | 17 Participants | 42 Participants |
| Sex: Female, Male Female | 17 Participants | 18 Participants | 35 Participants |
| Sex: Female, Male Male | 19 Participants | 13 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 36 | 0 / 31 |
| other Total, other adverse events | 20 / 36 | 20 / 31 |
| serious Total, serious adverse events | 3 / 36 | 1 / 31 |
Outcome results
Primary
Rate of Relapse
'Relapse' is defined as re-hospitalization (e.g., admission to an inpatient unit) for psychiatric symptoms following a previous hospital discharge by at least 2 weeks. The rate of relapse was calculated by dividing the number of re-hospitalizations per group (i.e., Placebo, Probiotic) by the number of participants per group so the unit is re-hospitalizations/participant.
Time frame: 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Rate of Relapse | .11 Proportion of Participants |
| Probiotic-Probio-Tec BG-VCap-6.5 | Rate of Relapse | .13 Proportion of Participants |