Gabapentin in Patients at Clinical Risk for Psychosis

Study Overview
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Brief Summary
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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
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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.

Official Title
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Gabapentin in Patients at Clinical Risk for Psychosis

Conditions
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Clinical High Risk for Psychosis

Intervention / Treatment
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* Drug: Gabapentin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: COPE patient between age of 18-30 Capacity to give informed consent 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: Metal implants in body or a history of metal working, or more than one past MRI scan with gadolinium Lifetime diagnosis of asthmatic symptoms within the past 3 years or known sensitivity to contrast agents Lifetime diagnosis of renal failure/disease Acute neurological, neuroendocrine,or medical disorder including renal insufficiency Lifetime diagnosis of hypertension or diabetes Intelligence Quotient (IQ) < 70 Acute risk for suicide and/or violence Pregnant, lactating Current abuse of substances (alcohol, cocaine, stimulants, cannabis, opiates, sedative hypnotics) 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) The Clinical Global Impressions Scale (CGI)-improvement score during study equal to or greater than 6

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gabapentin<br>Gabapentin 3600mg PO daily | Drug: Gabapentin<br>* Subjects will be treated with 400mg pills of gabapentin , titrating up to 3600mg per day, or 9 tablets (3 tabs tid)<br>|
| Placebo Comparator: Placebo<br>Matching placebo PO daily | Drug: Placebo<br>* Subjects will be treated with 400mg pills of placebo, titrating up to 3600mg per day, or 9 tablets (3 tabs tid)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 6 weeks | 
| 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. | 6 weeks |