Impulsive BehaviorNCT01158950
A Study of Neural Circuit Responses to Catechol-O-methyl Transferase (COMT) Inhibitors
A study testing Tolcapone in people with Impulsive Behavior, run by University of California, San Francisco at 2 sites in United States.
Trial summary
In this study, we seek to understand the effects of tolcapone, an FDA-approved COMT inhibitor, on reward choice and response inhibition, two measures we have previously shown to be altered in subjects with alcoholism. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Impulsive Behavior
- What is being tested?
- Tolcapone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 2 sitesUnited States
- Study dates
- Mar 2010to Dec 2018
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age between 18 and 50 years.
- Subject is right-handed.
- If female, subject is non-lactating, not pregnant, and using a reliable contraception method (i.e. abstinence, intrauterine device (IUD), hormonal birth control or barrier method).
- Subject is able to read and speak English.
- Subject is a high school graduate.
- Subject is able and willing to provide written and informed consent.
- Subject is able to understand and follow the instructions of the investigator, and understand all ratings scales.
- Subject is in good health.
Who cannot join
- Using cocaine, stimulants (other than THC, nicotine, \& caffeine)amphetamines, hallucinogens, "ecstasy", opiates, sedatives, pain pills, sleeping pills or other psychoactive drugs within two weeks of the start of the study OR more than 10 times in the last year.
- Has a current dependence on, or addiction to any psychoactive drug (except nicotine or caffeine) including alcohol.
- Clinically significant medical or psychiatric illness requiring treatment as determined by screening blood tests, medical history, and physical exam performed or reviewed by the study physician.
- Subject has a history of major alcohol related complications within the proceeding 2 years (liver failure/cirrhosis, pancreatitis, esophageal varices, etc.)
- Liver function test ≥ 3 times normal upper limit.
- BAC level > 0.05% at the beginning of screening visit (within margin of error of detection).
Show all 28Show fewer
- Has a neurological dysfunction or psychiatric disorder.
- Has severe low blood pressure.
- Has uncontrolled high blood pressure.
- Regular use of any of the drugs on the tolcapone or entacapone contraindications list OR within 2 weeks of drug administration.
- Regular use of SSRIs.
- Has an allergy or intolerance to tolcapone or entacapone.
- Subject has received an investigational drug within 30 days of screening visit.
- Subject is considered unsuitable for the study in the opinion of the investigator or study physician for any other reason.
- MRI Exclusion Criteria:
- The subject has metal (metal plates, pins, wires or screws, artificial limb, joint replacement or anything that might have been inserted during an operation) in his/her body.
- Subject has a pacemaker, defibrillator, stent, or any metal implants related to heart/blood flow problems.
- Subject has worked with metals (ie. metallurgy, metal shaving, welding, soldering, etc).
- Subject has been wounded with anything metal (bullet, shrapnel or metal filling).
- Has ever gotten a piece of metal in the eye.
- Has tattoos done with ink containing metal or permanent eyeliner.
- Wears color contact lenses.
- Has a hearing problem or hearing aid, cochlear implant or past ear surgery.
- Has any irremovable dental bridges, dental plates, metal caps or any other non-removable metal in the mouth.
- The subject is claustrophobic.
- The subject is pregnant. (women only)
- Has a IUD. (women only)
- Significantly overweight.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of California, Berkeley
Berkeley, California, 94704
UCSF: Ernest Gallo Clinic and Research Center
Emeryville, California, 94591
About this study
Official title: A Randomized, Double-Blind Study of Neural Circuit Responses to COMT Inhibitors
In this study, we seek to understand the effects of tolcapone, an FDA-approved COMT inhibitor, on reward choice and response inhibition, two measures we have previously shown to be altered in subjects with alcoholism. We now plan to test the hypothesis that COMT regulation of cortical dopamine levels is critical for regulation financial choices. Specifically, we propose that the lower levels of cortical dopamine present in individuals with the val158val COMT genotype reduces the inhibitory effect of frontal cortical areas on impulsive choice; an idea that extends previous hypotheses about the negative consequences of decreased prefrontal dopamine levels on inhibitory control. Moreover, this hypothesis suggests that inhibiting COMT may slow the degradation of dopamine and thereby decrease impulsivity.
Read the detailed description
Drug consumption despite adverse consequences is a defining feature of human addiction (DSM-IV-TR, 2004). Impulsivity, a tendency to choose an immediate action despite delayed adverse consequences, is a major risk factor for tobacco, psychostimulant, opioid and alcohol abuse. In humans, impulsivity can be quantified by presenting subjects with a choice between a small immediate monetary reward or a larger but delayed reward. We recently found that the val158val allele for the enzyme catechol-O-methyltransferase (COMT), which is associated with more rapid cortical dopamine catabolism and thus lower cortical dopamine levels correlates with greater impulsivity and greater fMRI blood oxygen level dependent (BOLD) signal in dorsolateral prefrontal and posterior parietal cortices.
The first phase of the study will involve healthy controls. The second phase of the study will involve abstinent alcoholics matched for age, education, and gender. Subjects will range in age between 18 and 50 years old.
- Conditions
- Impulsive Behavior
- Being tested
- Tolcapone, Placebo
- Medical subject headings
- Impulsive Behavior
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TolcaponeDrug
Also called Tasmar
Drug: Tolcapone 200mg (single dose) administered at study visit
PlaceboOther
Placebo (200mg) administered at study visit
| Study group | Role | What they receive |
|---|---|---|
| Tolcapone | Experimental | Drug: Tolcapone 200mg (single dose) administered at study visit Receives: Drug: Tolcapone |
| Placebo | Placebo comparator | Drug: Placebo for tolcapone administered at study visit Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation Between the Impulsive Choice Ratio and Baseline Impulsivity, as Measured With the Barratt Impulsiveness Scale
The presented value represents a correlation. Subjects completed a delay discounting task while functional MRI images were obtained. In this task, subjects made hypothetical choices between a smaller amount of money available sooner, and a larger amount of money available later. Performance on the delay discounting task, as assessed by the impulsive choice ratio, was determined for both the tolcapone and placebo sessions, and the difference between them (tolcapone minus placebo) was calculated. This difference value was then correlated with baseline scores on the Barratt Impulsiveness Scale.
Measured: 120 minutes after drug ingestion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2010 (estimated)
- Study startMar 2010
- Primary completionDec 2018
- Study completionDec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Impulsive BehaviorStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- University of California, Berkeley, United States Department of Defense
- Responsible party
- Sponsor
- Investigators
- Howard Fields, MD, PhD, Principal investigator, UCSF: Ernest Gallo Clinic and Research CenterJennifer Mitchell, PhD, Study director, UCSF: Ernest Gallo Clinic and Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01158950
- Sponsor's protocol ID
- 2009-12-461
- Other IDs
- W81XWH-10-1-0231
- Status last verified
- Nov 2020
- First submitted
- 7 Jul 2010
- Last updated
- 20 Nov 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Kayser AS, Allen DC, Navarro-Cebrian A, Mitchell JM, Fields HL. Dopamine, corticostriatal connectivity, and intertemporal choice. J Neurosci. 2012 Jul 4;32(27):9402-9. doi: 10.1523/JNEUROSCI.1180-12.2012.
PubMed 22764248
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind Study of Neural Circuit Responses to COMT Inhibitors
- ClinicalTrials.gov ID
- NCT01158950
- Acronym / sponsor ID
- 2009-12-461
- Conditions
- Impulsive Behavior
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- University of California, Berkeley, United States Department of Defense
- Study start
- Mar 2010 (actual)
- Primary completion
- Dec 2018 (actual)
- Study completion
- Dec 2018 (actual)
- First posted
- 8 Jul 2010 (estimated)
- Results
- Posted 20 Nov 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this study, we seek to understand the effects of tolcapone, an FDA-approved COMT inhibitor, on reward choice and response inhibition, two measures we have previously shown to be altered in subjects with alcoholism. We now plan to test the hypothesis that COMT regulation of cortical dopamine levels is critical for regulation financial choices. Specifically, we propose that the lower levels of cortical dopamine present in individuals with the val158val COMT genotype reduces the inhibitory effect of frontal cortical areas on impulsive choice; an idea that extends previous hypotheses about the negative consequences of decreased prefrontal dopamine levels on inhibitory control. Moreover, this hypothesis suggests that inhibiting COMT may slow the degradation of dopamine and thereby decrease impulsivity.
Detailed description
Drug consumption despite adverse consequences is a defining feature of human addiction (DSM-IV-TR, 2004). Impulsivity, a tendency to choose an immediate action despite delayed adverse consequences, is a major risk factor for tobacco, psychostimulant, opioid and alcohol abuse. In humans, impulsivity can be quantified by presenting subjects with a choice between a small immediate monetary reward or a larger but delayed reward. We recently found that the val158val allele for the enzyme catechol-O-methyltransferase (COMT), which is associated with more rapid cortical dopamine catabolism and thus lower cortical dopamine levels correlates with greater impulsivity and greater fMRI blood oxygen level dependent (BOLD) signal in dorsolateral prefrontal and posterior parietal cortices.
The first phase of the study will involve healthy controls. The second phase of the study will involve abstinent alcoholics matched for age, education, and gender. Subjects will range in age between 18 and 50 years old.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tolcapone | Experimental | Drug: TolcaponeDrug: Tolcapone 200mg (single dose) administered at study visit |
| Placebo | Placebo comparator | Other: PlaceboDrug: Placebo for tolcapone administered at study visit |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Age between 18 and 50 years.
- Subject is right-handed.
- If female, subject is non-lactating, not pregnant, and using a reliable contraception method (i.e. abstinence, intrauterine device (IUD), hormonal birth control or barrier method).
- Subject is able to read and speak English.
- Subject is a high school graduate.
Key exclusion criteria (28 listed)
- Using cocaine, stimulants (other than THC, nicotine, \& caffeine)amphetamines, hallucinogens, "ecstasy", opiates, sedatives, pain pills, sleeping pills or other psychoactive drugs within two weeks of the start of the study OR more than 10 times in the last year.
- Has a current dependence on, or addiction to any psychoactive drug (except nicotine or caffeine) including alcohol.
- Clinically significant medical or psychiatric illness requiring treatment as determined by screening blood tests, medical history, and physical exam performed or reviewed by the study physician.
- Subject has a history of major alcohol related complications within the proceeding 2 years (liver failure/cirrhosis, pancreatitis, esophageal varices, etc.)
- Liver function test ≥ 3 times normal upper limit.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TolcaponeAlso: TasmarDrug: Tolcapone 200mg (single dose) administered at study visit | Drug | Tolcapone |
| PlaceboPlacebo (200mg) administered at study visit | Other | Placebo |
Primary outcome
Correlation Between the Impulsive Choice Ratio and Baseline Impulsivity, as Measured With the Barratt Impulsiveness Scale
Time frame: 120 minutes after drug ingestion
The presented value represents a correlation. Subjects completed a delay discounting task while functional MRI images were obtained. In this task, subjects made hypothetical choices between a smaller amount of money available sooner, and a larger amount of money available later. Performance on the delay discounting task, as assessed by the impulsive choice ratio, was determined for both the tolcapone and placebo sessions, and the difference between them (tolcapone minus placebo) was calculated. This difference value was then correlated with baseline scores on the Barratt Impulsiveness Scale.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22764248Kayser AS, Allen DC, Navarro-Cebrian A, Mitchell JM, Fields HL. Dopamine, corticostriatal connectivity, and intertemporal choice. J Neurosci. 2012 Jul 4;32(27):9402-9. doi: 10.1523/JNEUROSCI.1180-12.2012.
Related trials for Impulsive Behavior
Not yet recruiting
Compulsive Eating and Brain's Reward System in Different Pathologies
PARKINSON DISEASE (Disorder), Bipolar 1 Disorder
Recruiting
Repetitive Transcranial Magnetic Stimulation Versus Theta Burst Stimulation on Impulsivity, Emotional Dysregulation, and Non-Suicidal Self-Injury in Borderline Personality Disorder Patients
Borderline Personality Disorder (BPD)
Recruiting
Trial of Social Work Services in Fracture Clinic Setting
Orthopaedic Fractures, Socioeconomic Factors
RecruitingObservational study
The Association Between Smartphone Overuse and Mechanical Neck Pain Among Galala University Students
Mechanical Neck Pain, Forward Head Posture (FHP)
Active, not recruiting
Pain Self-Management and Treatment Engagement for Patients Taking Opioids
Chronic Pain, Opioid Use Disorder
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.
Howard Fields, MD, PhD principal investigator
UCSF: Ernest Gallo Clinic and Research Center
Jennifer Mitchell, PhD study director
UCSF: Ernest Gallo Clinic and Research
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Tolcapone in people with Impulsive Behavior, run by University of California, San Francisco at 2 sites 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 8 inclusion and 28 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 20 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 20 Nov 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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.
What does the primary outcome measure?
Correlation Between the Impulsive Choice Ratio and Baseline Impulsivity, as Measured With the Barratt Impulsiveness Scale (time frame: 120 minutes after drug ingestion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01158950, which also lists 1 linked publication.
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 20 Nov 2020.