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| ID | Type | Description | Link |
|---|---|---|---|
| R01AA025365 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
| National Institute on Alcohol Abuse and Alcoholism (NIAAA) | NIH |
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The proposed 3-week, double-blind, crossover, proof of concept study aims to manipulate neurochemical dysfunctions characteristic of individuals with co-occurring BD and AUD (i.e., abnormally low prefrontal GABA and glutamate), using medications that have been shown to normalize cortical GABA (i.e., gabapentin) and glutamate (i.e., NAC) levels in past research, and to evaluate medication-related changes in response inhibition and alcohol cue-reactivity fMRI tasks as well as drinking and mood in individuals with AUD+BD.
Bipolar disorder (BD) is the Axis I psychiatric condition most strongly associated with substance use disorder (SUD); diagnostic co-occurrence is particularly high between BD and alcohol use disorder (AUD). Individuals with co-occurring SUD and BD (SUD+BD) have substantially worse clinical outcomes than those with either BD or SUD alone. Nonetheless, little is known about optimal treatment for individuals with SUD+BD; response to lithium appears to be poor, and only one double-blind, randomized, placebo-controlled trial of valproate has demonstrated improved drinking outcomes in this population. Traditionally, treatment trials for SUD+BD have investigated medications that have been FDA approved to treat either BD or SUD in hopes that such medications would prove efficacious in individuals with SUD+BD. A different approach to selecting, and ideally developing, medications for SUD+BD treatment trials would be to target neurochemical dysfunctions characteristic of individuals with both BD and SUD. Recent research by the current investigator has demonstrated unique disturbances in prefrontal gamma-Aminobutyric acid (GABA) and glutamate concentrations in this population using proton magnetic resonance spectroscopy (1H-MRS), with individuals with co-occurring alcohol dependence (AD) and BD having significantly lower levels of GABA and glutamate relative to individuals with BD alone, AD alone, or healthy controls. Lower levels of prefrontal GABA and glutamate were in turn associated with elevated impulsivity and alcohol craving. The proposed 3-week, double-blind, crossover, proof of concept study will evaluate: a) whether medications that have been demonstrated to normalize cortical GABA (i.e., gabapentin) and glutamate (i.e., N-Acetylcysteine [NAC]) concentrations in individuals with epilepsy and cocaine dependence, respectively, may similarly act to normalize prefrontal GABA and glutamate levels in individuals with AUD+BD, and b) whether normalization of prefrontal GABA and glutamate levels will be associated with improvements in functional brain activity to tasks that assess core neurobehavioral deficits of AUD and BD (i.e., response inhibition, alcohol cue-reactivity), as well as drinking and mood symptoms. Positive results may support investigation of gabapentin and/or NAC as adjunctive treatments for AUD+BD in large-scale, randomized clinical trials. Most importantly, the proposed study may provide successful demonstration of a neuro-behavioral, multimodal neuroimaging platform for evaluating the potential promise of GABAergic and glutamatergic drugs for AUD and/or BD, as well as other conditions marked by GABAergic/glutamatergic dysfunction.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Gabapentin, then N-Acetylcysteine, then Placebo Oral Capsule | Experimental | Three, 1-week conditions. Week 1 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 1,200mg gabapentin) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Gabapentin: 5 day trial of gabapentin with titration to 1,200mg Week 2 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 2,400mg N-acetylcysteine) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). N-Acetylcysteine: 5 day trial of N-acetylcysteine with titration to 2,400mg Week 3 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Placebo Oral Tablet: 5 day trial of matched placebo |
|
| N-Acetylcysteine, then Placebo Oral Capsule, then Gabapentin | Experimental | 3, 1 week conditions. Week 1 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 2,400mg N-acetylcysteine) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). N-Acetylcysteine: 5 day trial of N-acetylcysteine with titration to 2,400mg Week 2 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Placebo Oral Tablet: 5 day trial of matched placebo Week 3 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 1,200mg gabapentin) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Gabapentin: 5 day trial of gabapentin with titration to 1,200mg |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| N-Acetylcysteine | Drug | 5 day trial of N-acetylcysteine with titration to 2,400mg |
|
| Measure | Description | Time Frame |
|---|---|---|
| Prefrontal GABA+ Concentrations | Concentrations of GABA+, referenced to unsuppressed water and corrected for within-voxel CSF proportion, in dorsal anterior cingulate cortex measured via Proton Magnetic Resonance Spectroscopy (i.e., MEGA-PRESS). | Day 5 of each experimental condition |
| Prefrontal Glx Concentrations | Concentrations of Glx (i.e., glutamate + glutamine), referenced to unsuppressed water and corrected for within-voxel CSF proportion, in dorsal anterior cingulate cortex measured via Proton Magnetic Resonance Spectroscopy. | Day 5 of each experimental condition |
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Inclusion:
Exclusion:
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| Name | Affiliation | Role |
|---|---|---|
| James J Prisciandarao, Ph. D | Medical University of South Carolina | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical University of South Carolina | Charleston | South Carolina | 29425 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16310510 | Background | Altshuler LL, Bookheimer SY, Townsend J, Proenza MA, Eisenberger N, Sabb F, Mintz J, Cohen MS. Blunted activation in orbitofrontal cortex during mania: a functional magnetic resonance imaging study. Biol Psychiatry. 2005 Nov 15;58(10):763-9. doi: 10.1016/j.biopsych.2005.09.012. | |
| 7771669 | Background | Anton RF, Moak DH, Latham P. The Obsessive Compulsive Drinking Scale: a self-rated instrument for the quantification of thoughts about alcohol and drinking behavior. Alcohol Clin Exp Res. 1995 Feb;19(1):92-9. doi: 10.1111/j.1530-0277.1995.tb01475.x. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Gabapentin, Washout, Then N-Acetylcysteine, Washout, Then Placebo Oral Capsule, Washout | Three, 1-week conditions. Week 1 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 1,200mg gabapentin) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Gabapentin: 5 day trial of gabapentin with titration to 1,200mg Week 2 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 2,400mg N-acetylcysteine) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). N-Acetylcysteine: 5 day trial of N-acetylcysteine with titration to 2,400mg Week 3 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Placebo Oral Tablet: 5 day trial of matched placebo |
| FG001 | N-Acetylcysteine, Washout, Then Placebo Oral Capsule, Washout, Then Gabapentin, Washout | 3, 1 week conditions. Week 1 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 2,400mg N-acetylcysteine) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). N-Acetylcysteine: 5 day trial of N-acetylcysteine with titration to 2,400mg Week 2 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Placebo Oral Tablet: 5 day trial of matched placebo Week 3 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 1,200mg gabapentin) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Gabapentin: 5 day trial of gabapentin with titration to 1,200mg |
| FG002 | Placebo Oral Tablet, Washout, Then Gabapentin, Washout, Then N-Acetylcysteine, Washout | Three, 1-week conditions. Week 1 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Placebo Oral Tablet: 5 day trial of matched placebo Week 2 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 1,200mg gabapentin) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Gabapentin: 5 day trial of gabapentin with titration to 1,200mg Week 3 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 2,400mg N-acetylcysteine) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). N-Acetylcysteine: 5 day trial of N-acetylcysteine with titration to 2,400mg |
| FG003 | Placebo Oral Capsule, Washout, Then N-Acetylcysteine, Washout, Then Gabapentin, Washout | Three, 1-week conditions. Week 1 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Placebo Oral Tablet: 5 day trial of matched placebo Week 2 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 2,400mg N-acetylcysteine) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). N-Acetylcysteine: 5 day trial of N-acetylcysteine with titration to 2,400mg Week 3 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 1,200mg gabapentin) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Gabapentin: 5 day trial of gabapentin with titration to 1,200mg |
| FG004 | Gabapentin, Washout, Then Placebo Oral Capsule, Washout, Then N-Acetylcysteine, Washout | Three, 1-week conditions. Week 1 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 1,200mg gabapentin) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Gabapentin: 5 day trial of gabapentin with titration to 1,200mg Week 2 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Placebo Oral Tablet: 5 day trial of matched placebo Week 3 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 2,400mg N-acetylcysteine) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). N-Acetylcysteine: 5 day trial of N-acetylcysteine with titration to 2,400mg |
| FG005 | N-Acetylcysteine, Washout, Then Gabapentin, Washout, Then Placebo Oral Capsule, Washout | Three, 1-week conditions. Week 1 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 2,400mg N-acetylcysteine) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). N-Acetylcysteine: 5 day trial of N-acetylcysteine with titration to 2,400mg Week 2 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 1,200mg gabapentin) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Gabapentin: 5 day trial of gabapentin with titration to 1,200mg Week 3 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Placebo Oral Tablet: 5 day trial of matched placebo |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Gabapentin, Then N-Acetylcysteine, Then Placebo Oral Capsule | Three, 1-week conditions. Week 1 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 1,200mg gabapentin) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Gabapentin: 5 day trial of gabapentin with titration to 1,200mg Week 2 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 2,400mg N-acetylcysteine) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). N-Acetylcysteine: 5 day trial of N-acetylcysteine with titration to 2,400mg Week 3 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Placebo Oral Tablet: 5 day trial of matched placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Prefrontal GABA+ Concentrations | Concentrations of GABA+, referenced to unsuppressed water and corrected for within-voxel CSF proportion, in dorsal anterior cingulate cortex measured via Proton Magnetic Resonance Spectroscopy (i.e., MEGA-PRESS). | Overall number of participants analyzed includes participants who completed the entire medication condition (i.e. participants who started N-Acetylcysteine, Gabapentin, or Placebo Oral Tablet but who did not complete the MRI portion of the condition have been removed from outcome measure data analysis, but are included in other portions of this study record [Adverse Events, Demographics, etc.]). | Posted | Mean | Standard Deviation | mmol/kg | Day 5 of each experimental condition |
|
Adverse Event data were collected over each participant's total study duration. This duration was a 3-week period for each participant (i.e. 3, 1-week condition periods). Adverse event data collection took place for the entirety of the study which was 6 years.
At each study visit following the initial screening visit, study participants were assessed by the study medical doctor for any adverse events. Adverse events were recorded, rated on a severity scale, determined their relation to the study medication, and any treatment or intervention needed was discussed. The study medical doctor followed up with all previously reported adverse events at the following visits to determine if the events had ceased.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | N-Acetylcysteine | N-Acetylcysteine: 5 day trial of N-acetylcysteine with titration to 2,400mg |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| insomnia | Psychiatric disorders | MedDRA (10.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| James J. Prisciandaro, Ph.D. | Medical University of South Carolina | 843-792-1433 | priscian@musc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 30, 2023 | Nov 13, 2023 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000437 | Alcoholism |
| D001714 | Bipolar Disorder |
| ID | Term |
|---|---|
| D019973 | Alcohol-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D000111 | Acetylcysteine |
| D000077206 | Gabapentin |
| ID | Term |
|---|---|
| D003545 | Cysteine |
| D000603 | Amino Acids, Sulfur |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
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Double-Blind
| Placebo Oral Tablet, then Gabapentin, then N-Acetylcysteine |
| Placebo Comparator |
Three, 1-week conditions. Week 1 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Placebo Oral Tablet: 5 day trial of matched placebo Week 2 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 1,200mg gabapentin) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Gabapentin: 5 day trial of gabapentin with titration to 1,200mg Week 3 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 2,400mg N-acetylcysteine) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). N-Acetylcysteine: 5 day trial of N-acetylcysteine with titration to 2,400mg |
|
| Placebo Oral Capsule, then N-Acetylcysteine, then Gabapentin | Experimental | Three, 1-week conditions. Week 1 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Placebo Oral Tablet: 5 day trial of matched placebo Week 2 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 2,400mg N-acetylcysteine) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). N-Acetylcysteine: 5 day trial of N-acetylcysteine with titration to 2,400mg Week 3 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 1,200mg gabapentin) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Gabapentin: 5 day trial of gabapentin with titration to 1,200mg |
|
| Gabapentin, then Placebo Oral Capsule, then N-Acetylcysteine | Experimental | Three, 1-week conditions. Week 1 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 1,200mg gabapentin) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Gabapentin: 5 day trial of gabapentin with titration to 1,200mg Week 2 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Placebo Oral Tablet: 5 day trial of matched placebo Week 3 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 2,400mg N-acetylcysteine) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). N-Acetylcysteine: 5 day trial of N-acetylcysteine with titration to 2,400mg |
|
| N-Acetylcysteine, then Gabapentin, then Placebo Oral Capsule | Experimental | Three, 1-week conditions. Week 1 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 2,400mg N-acetylcysteine) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). N-Acetylcysteine: 5 day trial of N-acetylcysteine with titration to 2,400mg Week 2 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 1,200mg gabapentin) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Gabapentin: 5 day trial of gabapentin with titration to 1,200mg Week 3 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Placebo Oral Tablet: 5 day trial of matched placebo |
|
| Gabapentin | Drug | 5 day trial of gabapentin with titration to 1,200mg |
|
| Placebo Oral Tablet | Drug | 5 day trial of matched placebo |
|
| 19593171 | Background | Anton RF, Myrick H, Baros AM, Latham PK, Randall PK, Wright TM, Stewart SH, Waid R, Malcolm R. Efficacy of a combination of flumazenil and gabapentin in the treatment of alcohol dependence: relationship to alcohol withdrawal symptoms. J Clin Psychopharmacol. 2009 Aug;29(4):334-42. doi: 10.1097/JCP.0b013e3181aba6a4. |
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| 17210135 | Background | Bhagwagar Z, Wylezinska M, Jezzard P, Evans J, Ashworth F, Sule A, Matthews PM, Cowen PJ. Reduction in occipital cortex gamma-aminobutyric acid concentrations in medication-free recovered unipolar depressed and bipolar subjects. Biol Psychiatry. 2007 Mar 15;61(6):806-12. doi: 10.1016/j.biopsych.2006.08.048. Epub 2007 Jan 8. |
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| 42236678 | Derived | Prisciandaro JJ, Mellick WH, Hix S, Brand K, Tolliver BK, Anton RF. Glutamate- and GABA-targeted drugs for Cc-occurring bipolar and alcohol use disorders: a randomized, double-blind, placebo-controlled, crossover study of N-acetylcysteine, gabapentin, and placebo. Transl Psychiatry. 2026 Jun 3. doi: 10.1038/s41398-026-04112-4. Online ahead of print. |
| MRI Equipment Failure |
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| Inclimate Weather |
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| Physician Decision |
|
| Potential presence of non-MRI safe metal in body |
|
| Protocol Violation |
|
| Withdrawal by Subject |
|
| BG001 | N-Acetylcysteine, Then Placebo Oral Capsule, Then Gabapentin | 3, 1 week conditions. Week 1 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 2,400mg N-acetylcysteine) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). N-Acetylcysteine: 5 day trial of N-acetylcysteine with titration to 2,400mg Week 2 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Placebo Oral Tablet: 5 day trial of matched placebo Week 3 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 1,200mg gabapentin) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Gabapentin: 5 day trial of gabapentin with titration to 1,200mg |
| BG002 | Placebo Oral Tablet, Then Gabapentin, Then N-Acetylcysteine | Three, 1-week conditions. Week 1 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Placebo Oral Tablet: 5 day trial of matched placebo Week 2 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 1,200mg gabapentin) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Gabapentin: 5 day trial of gabapentin with titration to 1,200mg Week 3 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 2,400mg N-acetylcysteine) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). N-Acetylcysteine: 5 day trial of N-acetylcysteine with titration to 2,400mg |
| BG003 | Placebo Oral Capsule, Then N-Acetylcysteine, Then Gabapentin | Three, 1-week conditions. Week 1 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Placebo Oral Tablet: 5 day trial of matched placebo Week 2 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 2,400mg N-acetylcysteine) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). N-Acetylcysteine: 5 day trial of N-acetylcysteine with titration to 2,400mg Week 3 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 1,200mg gabapentin) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Gabapentin: 5 day trial of gabapentin with titration to 1,200mg |
| BG004 | Gabapentin, Then Placebo Oral Capsule, Then N-Acetylcysteine | Three, 1-week conditions. Week 1 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 1,200mg gabapentin) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Gabapentin: 5 day trial of gabapentin with titration to 1,200mg Week 2 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Placebo Oral Tablet: 5 day trial of matched placebo Week 3 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 2,400mg N-acetylcysteine) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). N-Acetylcysteine: 5 day trial of N-acetylcysteine with titration to 2,400mg |
| BG005 | N-Acetylcysteine, Then Gabapentin, Then Placebo Oral Capsule | Three, 1-week conditions. Week 1 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 2,400mg N-acetylcysteine) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). N-Acetylcysteine: 5 day trial of N-acetylcysteine with titration to 2,400mg Week 2 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 1,200mg gabapentin) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Gabapentin: 5 day trial of gabapentin with titration to 1,200mg Week 3 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Placebo Oral Tablet: 5 day trial of matched placebo |
| BG006 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Gabapentin | Each 1-week condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 1,200mg gabapentin) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Gabapentin: 5 day trial of gabapentin with titration to 1,200mg |
| OG002 | Placebo Oral Tablet | Each 1-week condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Placebo Oral Tablet: 5 day trial of matched placebo |
|
|
| Primary | Prefrontal Glx Concentrations | Concentrations of Glx (i.e., glutamate + glutamine), referenced to unsuppressed water and corrected for within-voxel CSF proportion, in dorsal anterior cingulate cortex measured via Proton Magnetic Resonance Spectroscopy. | Overall number of participants analyzed includes participants who completed the entire medication condition (i.e. participants who started N-Acetylcysteine, Gabapentin, or Placebo Oral Tablet but who did not complete the MRI portion of the condition have been removed from outcome measure data analysis, but are included in other portions of this study record [Adverse Events, Demographics, etc.]). | Posted | Mean | Standard Deviation | mmol/kg | Day 5 of each experimental condition |
|
|
|
| 0 |
| 48 |
| 0 |
| 48 |
| 10 |
| 48 |
| EG001 | Gabapentin | Gabapentin: 5 day trial of gabapentin with titration to 1,200mg | 0 | 48 | 0 | 48 | 9 | 48 |
| EG002 | Placebo Oral Tablet | Placebo Oral Tablet: 5 day trial of matched placebo | 0 | 51 | 0 | 51 | 6 | 51 |
| headache | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (10.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (10.0) | Systematic Assessment |
|
| Decreased Appetite | Metabolism and nutrition disorders | MedDRA (10.0) | Systematic Assessment |
|
| Lightheadedness | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
|
| Dyspnea | Cardiac disorders | MedDRA (10.0) | Systematic Assessment |
|
| Memory Impairment | Psychiatric disorders | MedDRA (10.0) | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
|
| Convulsion | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
|
| Irritability | General disorders | MedDRA (10.0) | Systematic Assessment |
|
| Mood Swings | Psychiatric disorders | MedDRA (10.0) | Systematic Assessment |
|
| Dissociation | Psychiatric disorders | MedDRA (10.0) | Systematic Assessment |
|
| Teeth Grinding | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Skin Abrasion | Injury, poisoning and procedural complications | MedDRA (10.0) | Systematic Assessment |
|
| Skin Odor | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Gastroesophageal Reflux Disease (GERD) | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
|
Not provided
Not provided
| D000068105 | Bipolar and Related Disorders |
| D019964 | Mood Disorders |
| D000596 |
| Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000588 | Amines |
| D005680 | gamma-Aminobutyric Acid |
| D000613 | Aminobutyrates |
| D002087 | Butyrates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D003509 | Cyclohexanecarboxylic Acids |
| D000146 | Acids, Carbocyclic |
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |