HealthyNCT00094510
Effect of Gabapentin on GABA Concentration and Emotional Processing
An observational study of Healthy, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
This study will use magnetic resonance spectroscopy (MRS) and the drug gabapentin to examine the role of the brain chemical gamma-amino-butyric acid (GABA) in regulating emotions in healthy people. Gabapentin, which is used to treat epilepsy, increases GABA concentrations in the brain. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Healthy
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Oct 2004to 3 Sep 2010
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Family history of mental illness (mood and anxiety disorders, schizophrenia and other psychotic disorders, substance abuse disorders) will be obtained in all 1st degree relatives using the Family Interview of Genetic Studies.
- Healthy Control Samples: 34 healthy subjects (ages 18-60) without a known personal or family history of psychiatric disorders in first-degree relatives will be selected.
Who cannot join
- Pregnant females will be excluded due to the potential risk of magnetic field exposure during pregnancy.
- If any subject appears incapable of providing informed consent, they will be excluded from the study.
- Subjects must not have taken centrally active medication for at least 3 weeks prior to the study.
- Subjects will also be excluded if they have: a) medical or neurological illnesses likely to affect physiology or anatomy, i.e. hypertension, cardiovascular disorders, b) a history of drug (including benzodiazepines [BZD]) or alcohol abuse, c) smokers, d) serious suicidal ideation or behavior, e) lactose intolerance, f) caffeine dependency, g) history of allergic reaction to GBP, and h) general MRI exclusion criteria.
- Subjects must exhibit no or only moderate alcohol use.
- Subjects beyond age 60 are excluded because of slower elimination of GBP in older adults, and the age-related increase in brain structural abnormalities.
- In women, there are additional exclusion criteria: i) current pregnancy (as documented by pregnancy testing at screening or at days of the challenge studies), j) current breast feeding, k) lack of reliable contraception method.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: The Effect of Gabapentin on Prefrontal GABA Concentration and Emotional Processing in Healthy Humans
This study will use magnetic resonance spectroscopy (MRS) and the drug gabapentin to examine the role of the brain chemical gamma-amino-butyric acid (GABA) in regulating emotions in healthy people. Gabapentin, which is used to treat epilepsy, increases GABA concentrations in the brain. MRS, similar to magnetic resonance imaging (MRI), is a diagnostic test that uses a magnetic field and radio waves to produce images of the brain.
Non-smoking, healthy normal volunteers between 18 and 60 years of age may be eligible for this study. Candidates are screened with a medical history and physical examination, psychiatric evaluation, blood and urine tests, and an electrocardiogram (EKG).
At three separate clinic visits, participants are given either gabapentin or a placebo (an inactive look-alike capsule). They take placebo at one visit, 600 mg of gabapentin at another visit, and 1200 mg of gabapentin at another visit. One hour after taking the capsules, the amount of GABA in the brain is measured by MRS. For this procedure, the subject lies on a table that moves into the MRI scanner (a narrow cylinder), wearing earplugs to muffle loud knocking and thumping sounds that occur during the scanning process. The procedure lasts about 45 to 60 minutes, during which the patient is asked to lie still for up to a few minutes at a time.
Read the detailed description
Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the forebrain structures, and the GABAergic system has been found to have roles in attentional and learning processes, recognition of aversive stimuli, and regulation of emotion and behavior. Decreases in GABA have been associated with seizures, anxiety and mood disorders. Enhancement of GABA may result in anticonvulsive, anxiolytic, and mood-stabilizing effects.
The GABA system has been proposed as a target for novel antidepressant and mood-stabilizing treatments. Recent studies suggest a GABAergic dysfunction in mood and anxiety disorders. Specifically, reduced GABA levels have been found in the occipital cortex of patients with major depression and panic disorder; and after therapy with selective serotonin reuptake inhibitors, an increase in occipital GABA concentrations has been observed in depressed patients and healthy volunteers.
Gabapentin (GBP) is a relatively novel drug that has been approved for the treatment of epilepsy. The effects of GBP on brain amino acid neurotransmitters are not completely understood. GBP significantly increases brain GABA levels in humans after one hour of the first oral dose, although it does not seem to directly affect GABA-specific enzymes, GABA receptors, and GABA uptake. In vitro, GBP stimulates the enzyme glutamic acid decarboxylase that is involved in the synthesis of GABA.
To date, studies that have examined the mechanism of action of GABA enhancing compounds using magnetic resonance spectroscopy (MRS) measured GABA exclusively in the occipital cortex due to technical limitations. Not surprisingly, associations between occipital GABA levels and cognitive measures and psychiatric symptom severity have not been found.
Thanks to a novel MRS method developed by GE and implemented by NIH, reliable measurements of prefrontal GABA levels are now available. The current study is designed to estimate prefrontal GABA levels in a placebo-controlled double-blind study of GBP. It is aimed at evaluating the novel MRS method to estimate prefrontal GABA levels. Prefrontal GABA levels will be related to prefrontal functions including facial emotion recognition and response control. GABA MRS after GBP/placebo may be used as challenge paradigm for future studies aimed at elucidating GABAergic dysfunctions in mood and anxiety disorders. 10 healthy medication-free human subjects will be examined by GABA magnetic resonance spectroscopy in a controlled trial using placebo, 600mg, and 1200mg GBP.
Given the potential role of GABA in the physiologic stress response, this protocol includes a pilot study that compares prefrontal GABA levels between shock/threat-of-shock and no-threat conditions in healthy volunteers. This part of the study may contribute to the elucidation of the role of the prefrontal GABAergic system in the processing of acute stress.
- Conditions
- Healthy
- Keywords
- Prefrontal GABA, Stress, Emotion Recognition, Differential Reward, Gabapentin, GABA, Prefrontal Cortex, Emotional Processing, Healthy Humans, Healthy Volunteer, HV
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2004 (estimated)
- Study start14 Oct 2004
- Study completion3 Sep 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by National Institute of Mental Health (NIMH)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00094510
- Sponsor's protocol ID
- 050006
- Other IDs
- 05-M-0006
- Status last verified
- 3 Sep 2010
- First submitted
- 19 Oct 2004
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Petroff OA. GABA and glutamate in the human brain. Neuroscientist. 2002 Dec;8(6):562-73. doi: 10.1177/1073858402238515.
PubMed 12467378McDonagh J, Stephen LJ, Dolan FM, Parks S, Dutton GN, Kelly K, Keating D, Sills GJ, Brodie MJ. Peripheral retinal dysfunction in patients taking vigabatrin. Neurology. 2003 Dec 23;61(12):1690-4. doi: 10.1212/01.wnl.0000098938.80082.25.
PubMed 14694031Petroff OA, Hyder F, Rothman DL, Mattson RH. Effects of gabapentin on brain GABA, homocarnosine, and pyrrolidinone in epilepsy patients. Epilepsia. 2000 Jun;41(6):675-80. doi: 10.1111/j.1528-1157.2000.tb00227.x.
PubMed 10840398
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Gabapentin on Prefrontal GABA Concentration and Emotional Processing in Healthy Humans
- ClinicalTrials.gov ID
- NCT00094510
- Acronym / sponsor ID
- 050006
- Conditions
- Healthy
- Keywords
- Prefrontal GABA, Stress, Emotion Recognition, Differential Reward, Gabapentin, GABA, Prefrontal Cortex, Emotional Processing
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 14 Oct 2004
- Study completion
- 3 Sep 2010
- First posted
- 20 Oct 2004 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will use magnetic resonance spectroscopy (MRS) and the drug gabapentin to examine the role of the brain chemical gamma-amino-butyric acid (GABA) in regulating emotions in healthy people. Gabapentin, which is used to treat epilepsy, increases GABA concentrations in the brain. MRS, similar to magnetic resonance imaging (MRI), is a diagnostic test that uses a magnetic field and radio waves to produce images of the brain.
Non-smoking, healthy normal volunteers between 18 and 60 years of age may be eligible for this study. Candidates are screened with a medical history and physical examination, psychiatric evaluation, blood and urine tests, and an electrocardiogram (EKG).
At three separate clinic visits, participants are given either gabapentin or a placebo (an inactive look-alike capsule). They take placebo at one visit, 600 mg of gabapentin at another visit, and 1200 mg of gabapentin at another visit. One hour after taking the capsules, the amount of GABA in the brain is measured by MRS. For this procedure, the subject lies on a table that moves into the MRI scanner (a narrow cylinder), wearing earplugs to muffle loud knocking and thumping sounds that occur during the scanning process. The procedure lasts about 45 to 60 minutes, during which the patient is asked to lie still for up to a few minutes at a time.
Detailed description
Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the forebrain structures, and the GABAergic system has been found to have roles in attentional and learning processes, recognition of aversive stimuli, and regulation of emotion and behavior. Decreases in GABA have been associated with seizures, anxiety and mood disorders. Enhancement of GABA may result in anticonvulsive, anxiolytic, and mood-stabilizing effects.
The GABA system has been proposed as a target for novel antidepressant and mood-stabilizing treatments. Recent studies suggest a GABAergic dysfunction in mood and anxiety disorders. Specifically, reduced GABA levels have been found in the occipital cortex of patients with major depression and panic disorder; and after therapy with selective serotonin reuptake inhibitors, an increase in occipital GABA concentrations has been observed in depressed patients and healthy volunteers.
Gabapentin (GBP) is a relatively novel drug that has been approved for the treatment of epilepsy. The effects of GBP on brain amino acid neurotransmitters are not completely understood. GBP significantly increases brain GABA levels in humans after one hour of the first oral dose, although it does not seem to directly affect GABA-specific enzymes, GABA receptors, and GABA uptake. In vitro, GBP stimulates the enzyme glutamic acid decarboxylase that is involved in the synthesis of GABA.
To date, studies that have examined the mechanism of action of GABA enhancing compounds using magnetic resonance spectroscopy (MRS) measured GABA exclusively in the occipital cortex due to technical limitations. Not surprisingly, associations between occipital GABA levels and cognitive measures and psychiatric symptom severity have not been found.
Thanks to a novel MRS method developed by GE and implemented by NIH, reliable measurements of prefrontal GABA levels are now available. The current study is designed to estimate prefrontal GABA levels in a placebo-controlled double-blind study of GBP. It is aimed at evaluating the novel MRS method to estimate prefrontal GABA levels. Prefrontal GABA levels will be related to prefrontal functions including facial emotion recognition and response control. GABA MRS after GBP/placebo may be used as challenge paradigm for future studies aimed at elucidating GABAergic dysfunctions in mood and anxiety disorders. 10 healthy medication-free human subjects will be examined by GABA magnetic resonance spectroscopy in a controlled trial using placebo, 600mg, and 1200mg GBP.
Given the potential role of GABA in the physiologic stress response, this protocol includes a pilot study that compares prefrontal GABA levels between shock/threat-of-shock and no-threat conditions in healthy volunteers. This part of the study may contribute to the elucidation of the role of the prefrontal GABAergic system in the processing of acute stress.
Study design
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Family history of mental illness (mood and anxiety disorders, schizophrenia and other psychotic disorders, substance abuse disorders) will be obtained in all 1st degree relatives using the Family Interview of Genetic Studies.
- Healthy Control Samples: 34 healthy subjects (ages 18-60) without a known personal or family history of psychiatric disorders in first-degree relatives will be selected.
Key exclusion criteria (7 listed)
- Pregnant females will be excluded due to the potential risk of magnetic field exposure during pregnancy.
- If any subject appears incapable of providing informed consent, they will be excluded from the study.
- Subjects must not have taken centrally active medication for at least 3 weeks prior to the study.
- Subjects will also be excluded if they have: a) medical or neurological illnesses likely to affect physiology or anatomy, i.e. hypertension, cardiovascular disorders, b) a history of drug (including benzodiazepines [BZD]) or alcohol abuse, c) smokers, d) serious suicidal ideation or behavior, e) lactose intolerance, f) caffeine dependency, g) history of allergic reaction to GBP, and h) general MRI exclusion criteria.
- Subjects must exhibit no or only moderate alcohol use.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 12467378Petroff OA. GABA and glutamate in the human brain. Neuroscientist. 2002 Dec;8(6):562-73. doi: 10.1177/1073858402238515.
- Background: PubMed 14694031McDonagh J, Stephen LJ, Dolan FM, Parks S, Dutton GN, Kelly K, Keating D, Sills GJ, Brodie MJ. Peripheral retinal dysfunction in patients taking vigabatrin. Neurology. 2003 Dec 23;61(12):1690-4. doi: 10.1212/01.wnl.0000098938.80082.25.
- Background: PubMed 10840398Petroff OA, Hyder F, Rothman DL, Mattson RH. Effects of gabapentin on brain GABA, homocarnosine, and pyrrolidinone in epilepsy patients. Epilepsia. 2000 Jun;41(6):675-80. doi: 10.1111/j.1528-1157.2000.tb00227.x.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Healthy, run by National Institute of Mental Health (NIMH) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00094510, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2017.