Clinical High Risk for Psychosis
Conditions
Brief summary
The purpose of this study is to test the effects of the drug gabapentin on brain function thought to be important in the development of schizophrenia. Researchers think that treating a brain region with gabapentin (the hippocampus) may reduce the risk for developing schizophrenia.
Detailed description
Six week, single site, proof-of concept, randomized double-blind placebo-controlled pilot study to examine the effects of moderate dose gabapentin (3600mg) in n= 100 putatively prodromal patients on hippocampal activity.
Interventions
DRUGGabapentin
Subjects will be treated with 400mg pills of gabapentin , titrating up to 3600mg per day, or 9 tablets (3 tabs tid)
DRUGPlacebo
Subjects will be treated with 400mg pills of placebo, titrating up to 3600mg per day, or 9 tablets (3 tabs tid)
Sponsors
New York State Psychiatric Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 30 Years
Healthy volunteers
No
Inclusion criteria
1. COPE patient between age of 18-30 2. Capacity to give informed consent 3. Currently using a reliable method of birth control (female) (condom plus spermicide, diaphragm plus spermicide, IUD, birth control pills, norplant, vasectomy in partner)
Exclusion criteria
1. Metal implants in body or a history of metal working, or more than one past MRI scan with gadolinium 2. Lifetime diagnosis of asthmatic symptoms within the past 3 years or known sensitivity to contrast agents 3. Lifetime diagnosis of renal failure/disease 4. Acute neurological, neuroendocrine,or medical disorder including renal insufficiency 5. Lifetime diagnosis of hypertension or diabetes 6. Intelligence Quotient (IQ) \< 70 7. Acute risk for suicide and/or violence 8. Pregnant, lactating 9. Current abuse of substances (alcohol, cocaine, stimulants, cannabis, opiates, sedative hypnotics) 10. Current use or anticipated need for antipsychotics or mood stabilizers (all antipsychotics, also Depakote, lithium, lamotrigine, pregabalin or any med with a mechanism of action like gabapentin) 11. The Clinical Global Impressions Scale (CGI)-improvement score during study equal to or greater than 6
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Left CA1 Cerebral Blood Volume (CBV) (MRI Measure) | 6 weeks | Change from 6 week follow up minus baseline of left CA1 CBV (MRI measure) in patients who receive active drug vs. placebo, after 6 weeks of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Positive, Negative, Disorganization, and General Symptoms Over Time as Measured by the Structured Interview for Psychosis-Risk Syndromes (SIPS)/the Scale of Psychosis-Risk Symptoms (SOPS) | 6 weeks | Exploratory analyses will be conducted examining the effects of gabapentin on changes in Positive symptoms (P scores), negative symptoms (N scores) and general symptoms (G scores) and disorganization symptoms (D scores) compared to placebo. There are 19 items on the SIPS. Each item is scored 0-6. There are 5 positive symptom items (range=0-30), 6 negative symptom items (range=0-36), 4 disorganization symptom items (range=0-24), and 4 general symptom items (range=0-24). The range of scores is 0-114. A lower score at baseline indicates less symptoms, and therefore a negative change over the 6 week period indicates an improvement, and a positive change indicates worsening of symptoms. |
| Change in Cognitive Function (Hippocampal-dependent Verbal Memory) as Measured by the California Verbal Learning Test-Second Edition (CLVT-II) | 6 weeks | Exploratory analyses will be conducted on changes between gabapentin and placebo groups on the California Verbal Learning Test-Second Edition (CLVT-II) measures. The unit measured was 'learning slope', where higher slope indicates better memory and a lower slope indicates poorer memory. |
Countries
United States
Participant flow
Recruitment details
9 individuals signed consent and underwent screening procedures for the study. 6 of the 9 were randomized to receive gabapentin/placebo
Participants by arm
| Arm | Count |
|---|---|
| Gabapentin Gabapentin 3600mg PO daily
Gabapentin: Subjects will be treated with 400mg pills of gabapentin , titrating up to 3600mg per day, or 9 tablets (3 tabs tid) | 3 |
| Placebo Matching placebo PO daily
Placebo: Subjects will be treated with 400mg pills of placebo, titrating up to 3600mg per day, or 9 tablets (3 tabs tid) | 3 |
| Total | 6 |
Baseline characteristics
| Characteristic | Gabapentin | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 3 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 3 Participants | 6 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 |
| other Total, other adverse events | 1 / 3 | 0 / 3 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 |
Outcome results
Primary
Change in Left CA1 Cerebral Blood Volume (CBV) (MRI Measure)
Change from 6 week follow up minus baseline of left CA1 CBV (MRI measure) in patients who receive active drug vs. placebo, after 6 weeks of treatment.
Time frame: 6 weeks
Population: While 6 participants received gabapentin or placebo, 1 participant data was excluded due to low quality of scans. Only 5 participants data were analyzes (2 in gabapentin group, 3 in placebo group)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gabapentin | Change in Left CA1 Cerebral Blood Volume (CBV) (MRI Measure) | -0.005 percent change | Standard Error 0.388 |
| Placebo | Change in Left CA1 Cerebral Blood Volume (CBV) (MRI Measure) | 0.38 percent change | Standard Error 0.317 |
Secondary
Change in Cognitive Function (Hippocampal-dependent Verbal Memory) as Measured by the California Verbal Learning Test-Second Edition (CLVT-II)
Exploratory analyses will be conducted on changes between gabapentin and placebo groups on the California Verbal Learning Test-Second Edition (CLVT-II) measures. The unit measured was 'learning slope', where higher slope indicates better memory and a lower slope indicates poorer memory.
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Gabapentin | Change in Cognitive Function (Hippocampal-dependent Verbal Memory) as Measured by the California Verbal Learning Test-Second Edition (CLVT-II) | 0.1 Change in raw learning slope |
| Placebo | Change in Cognitive Function (Hippocampal-dependent Verbal Memory) as Measured by the California Verbal Learning Test-Second Edition (CLVT-II) | -0.3 Change in raw learning slope |
Secondary
Change in Positive, Negative, Disorganization, and General Symptoms Over Time as Measured by the Structured Interview for Psychosis-Risk Syndromes (SIPS)/the Scale of Psychosis-Risk Symptoms (SOPS)
Exploratory analyses will be conducted examining the effects of gabapentin on changes in Positive symptoms (P scores), negative symptoms (N scores) and general symptoms (G scores) and disorganization symptoms (D scores) compared to placebo. There are 19 items on the SIPS. Each item is scored 0-6. There are 5 positive symptom items (range=0-30), 6 negative symptom items (range=0-36), 4 disorganization symptom items (range=0-24), and 4 general symptom items (range=0-24). The range of scores is 0-114. A lower score at baseline indicates less symptoms, and therefore a negative change over the 6 week period indicates an improvement, and a positive change indicates worsening of symptoms.
Time frame: 6 weeks
Population: For general symptom score (G score) and disorganization symptom (D score), 1 participant had missing data and was not included in the data reporting.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Gabapentin | Change in Positive, Negative, Disorganization, and General Symptoms Over Time as Measured by the Structured Interview for Psychosis-Risk Syndromes (SIPS)/the Scale of Psychosis-Risk Symptoms (SOPS) | P score change | -1.5 score on a scale |
| Gabapentin | Change in Positive, Negative, Disorganization, and General Symptoms Over Time as Measured by the Structured Interview for Psychosis-Risk Syndromes (SIPS)/the Scale of Psychosis-Risk Symptoms (SOPS) | N score change | -1 score on a scale |
| Gabapentin | Change in Positive, Negative, Disorganization, and General Symptoms Over Time as Measured by the Structured Interview for Psychosis-Risk Syndromes (SIPS)/the Scale of Psychosis-Risk Symptoms (SOPS) | G score change | -1.5 score on a scale |
| Gabapentin | Change in Positive, Negative, Disorganization, and General Symptoms Over Time as Measured by the Structured Interview for Psychosis-Risk Syndromes (SIPS)/the Scale of Psychosis-Risk Symptoms (SOPS) | D score change | 2 score on a scale |
| Placebo | Change in Positive, Negative, Disorganization, and General Symptoms Over Time as Measured by the Structured Interview for Psychosis-Risk Syndromes (SIPS)/the Scale of Psychosis-Risk Symptoms (SOPS) | D score change | -2.5 score on a scale |
| Placebo | Change in Positive, Negative, Disorganization, and General Symptoms Over Time as Measured by the Structured Interview for Psychosis-Risk Syndromes (SIPS)/the Scale of Psychosis-Risk Symptoms (SOPS) | P score change | 0.66 score on a scale |
| Placebo | Change in Positive, Negative, Disorganization, and General Symptoms Over Time as Measured by the Structured Interview for Psychosis-Risk Syndromes (SIPS)/the Scale of Psychosis-Risk Symptoms (SOPS) | G score change | 0.5 score on a scale |
| Placebo | Change in Positive, Negative, Disorganization, and General Symptoms Over Time as Measured by the Structured Interview for Psychosis-Risk Syndromes (SIPS)/the Scale of Psychosis-Risk Symptoms (SOPS) | N score change | -1.66 score on a scale |