HealthyPhase 2CTNANCT01585168
Functional Neuroimaging of Alcoholism Vulnerability (PIT)
A Phase 2 study testing Memantine in people with Healthy, run by Yale University at 1 site in United States.
Trial summary
This project compares Family History Positive (FHP) for alcoholism subjects to matched Family History Negative (FHN) subjects derived from the project Principal Investigator's National Institute on Alcohol Abuse and Alcoholism-funded longitudinal study of drinking behavior in a 2000 college freshman population (known… Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Memantine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 71 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2011to May 2016
- Phase
- Phase 2
- 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 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Biological father with a history of Alcoholism
- A least 1 other first- or second-degree relative with a history of Alcoholism.
Who cannot join
- Cannot be an only child
- A diagnosis of DSM-IV-TR Axis I psychotic disorders screened with the Mini International Neuropsychiatric Interview (MINI), done in the BARCS study (with the exception of Alcohol Abuse)
- Report of psychotic disorder in a 1º relative
- Prenatal exposure to alcohol (mother reported to drink 3 or more drinks on an occasion or more than 3 times per month during pregnancy
- Not speaking English fluently or being a non-native English speaker, or being educated in a primary language other than English >grade 1
- Mental retardation (Full Scale IQ<70)
Show all 13Show fewer
- Traumatic brain injury with loss of consciousness > 30 minutes or concussion in last 30 days
- Presence or history of any medical/neurologic illness that may affect brain physiology (e.g., epilepsy, Multiple Sclerosis), including focal brain lesion seen on structural MRI (all structural scans are read by a licensed radiologist)
- Current pregnancy (all females will be tested with urine screens on the day of MRI)
- Any positive alcohol screen will result in exclusion
- Inability to comprehend the consent form appropriately
- Other specific fMRI exclusions include metal devices, clips or fragments in body (orbital x-ray performed if needed)
- Female participants under 125 pounds will be excluded from participating due to the strength and side effects in this segment of the population.
Trial locations and contacts
1 site in 1 country.
United States1 site
Olin Neuropsychiatry Research Center at the Institute of Living, Hartford Hospital
Hartford, Connecticut, 06106
About this study
Official title: Functional Neuroimaging of Alcoholism Vulnerability: Glutamate, Reward, Impulsivity and Pavlovian-to-Instrumental Transfer (PIT)
This project compares Family History Positive (FHP) for alcoholism subjects to matched Family History Negative (FHN) subjects derived from the project Principal Investigator's National Institute on Alcohol Abuse and Alcoholism-funded longitudinal study of drinking behavior in a 2000 college freshman population (known as the Brain and Alcohol Research in College Students study (BARCS)). The age of these subjects is a valuable one at which to capture the transition from harmful use to abuse/dependence. This project explores the effects of memantine in a double-blind, randomized, counterbalanced manner on alcoholism risk-relevant tasks. More specifically, this project studies functional MRI tasks related to different aspects of reward and/or impulsivity-related behavior in different contexts, compares the underlying neural circuitry across tasks, and uses a pharmacologic probe of the glutamatergic system to examine NMDA/DA interactions. The combined measures provide the opportunity to advance our understanding of specific aspects of brain function related to familial alcoholism vulnerability in an already well-characterized population as some members evolve into alcohol abuse. In addition to conventional within-task analyses, functional network connectivity and allied approaches will be used to examine brain networks across tasks.
The investigators will study adult male and female subjects in equal numbers who are either offspring of an alcoholic parent or are FHN matched controls. The investigators will recruit and assess a total of 84 (42 FHP and 42 matched FHN) subjects between the ages of 18-21 years on initial BARCS contact. The investigators will use 4 cognitive tasks during the functional MRI (fMRI) which include: 1) a Monetary Incentive Delay Task that distinguishes networks engaged in motivational (anticipation) and consummatory (outcome) components of reward processing; 2) a Go/No-Go Task that measures the ability to inhibit response to a pre-potent stimulus; 3) an Alcohol Cue Reactivity Task that examines Nucleus Accumbens response to alcohol-related versus matched soft drink stimuli; and 4) a Pavlovian-to-Instrumental Transfer (PIT) Task that dissects a component of the Monetary Incentive Delay (MID) Task, and provides an imaging assay of a transfer-like process that can be related to real-world drinking behavior, thus informing upon and extending the key findings from CTNA-2.
- Conditions
- Healthy
- Being tested
- Memantine, Placebo
- Keywords
- Reward Circuitry, Impulsivity, Family History of Alcoholism, NMDA/DA Interactions
- Medical subject headings
- Impulsive Behavior
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MemantineDrug
Memantine is a low-side-effect NMDA receptor antagonist usually administered therapeutically to elderly persons with moderately severe Alzheimer's disease in typical doses of 10-20 mg daily. In this study, single doses of 40 mg are administered.
PlaceboDrug
Identically appearing sugar pill, given orally
| Study group | Role | What they receive |
|---|---|---|
| Family history positive, Memantine first, then placebo | Experimental | Memantine is a low-side-effect NMDA receptor antagonist usually administered therapeutically to elderly persons with moderately severe Alzheimer's disease in typical doses of 10-20 mg daily. In this study, single doses of 40 mg are administered. Receives: Drug: Memantine; Drug: Placebo |
| Family history positive, placebo first, then Memantine | Placebo comparator | Memantine is a low-side-effect NMDA receptor antagonist usually administered therapeutically to elderly persons with moderately severe Alzheimer's disease in typical doses of 10-20 mg daily. In this study, single doses of 40 mg are administered. Receives: Drug: Memantine; Drug: Placebo |
| Family history negative, Memantine first, then placebo | Experimental | Memantine is a low-side-effect NMDA receptor antagonist usually administered therapeutically to elderly persons with moderately severe Alzheimer's disease in typical doses of 10-20 mg daily. In this study, single doses of 40 mg are administered. Receives: Drug: Memantine; Drug: Placebo |
| Family history negative, placebo first, then Memantine | Placebo comparator | Memantine is a low-side-effect NMDA receptor antagonist usually administered therapeutically to elderly persons with moderately severe Alzheimer's disease in typical doses of 10-20 mg daily. In this study, single doses of 40 mg are administered. Receives: Drug: Memantine; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Blood Oxygenation Level Dependent (BOLD) Activation in the Amygdala During "Win" Monetary Incentive Delay (MID) Task Between Placebo and Study Medication
All participants completed the fMRI Monetary Incentive Delay task on each study day. During the task, participants needed to select the correct response during "win" and "lose" conditions by pressing a button on a button box in the MRI. Participant's BOLD activation response (A measurement of oxygen level that is released to neurons since areas of the brain that are thought to be more "active" or involved in certain tasks require more oxygen to perform the tasks.) was measured while they performed the task in MRI scanner.
Measured: 4 hours post intervention on each study day, separated by 1 week to 1 month
Change in Blood Oxygenation Level Dependent (BOLD) Activation in Anterior Cingulate Cortex During "Loss" Condition of Monetary Incentive Delay (MID) Task Between Placebo and Study Medication
All participants completed the fMRI Monetary Incentive Delay task on each study day. During the task, participants needed to select the correct response during "win" and "lose" conditions by pressing a button on a button box in the MRI. Participant's BOLD activation response (A measurement of oxygen level that is released to neurons since areas of the brain that are thought to be more "active" or involved in certain tasks require more oxygen to perform the tasks.) was measured while they performed the task in MRI scanner.
Measured: 4 hours post intervention on each study day, separated by 1 week to 1 month
Secondary outcomes (2)
Change in Impulsive Behavior as Measured on the Balloon Analog Risk Task (BART) Computerized Task Between Placebo and Study Medication
All participants completed the BART task approximately 3 hours post drug administration on both study visits. Study days were approximately 1 week to 1 month a part. BART is a computer decision-making task that measures risk taking. Participants are presented with a series of "balloons." The object is to earn as much money as possible by pumping the balloon without popping it. The point of explosion varies from trial to trial and costs participants the money they have earned in that trial.
Measured: 3 hours post intervention on each study day, separated by 1 week to 1 month
Change in Impulsive Behavior as Measured on the Experimental Discounting Delay (EDT) Computerized Task Between Placebo and Study Medication
All participants completed the EDT task approximately 3 hours post drug administration on both study visits. Study days were approximately 1 week to 1 month a part. EDT is a delay-discounting task that exposes participants to choice consequences during test administration. The EDT involves multiple blocks of choices, one for each delay. Choices are made between a standard amount that is delivered immediately and is certain and a probable amount that is delayed and uncertain.
Measured: 3 hours post intervention on each study day, separated by 1 week to 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2012 (estimated)
- Study startDec 2011
- Primary completionMay 2016
- Study completionMay 2016
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.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- All subjects received both the study drug and placebo. Family history was the main variable of interest, and randomization was stratified by this variable.
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 71 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Godfrey D Pearlson, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01585168
- Sponsor's protocol ID
- 1106008650
- Acronym
- CTNA
- Status last verified
- Feb 2021
- First submitted
- 23 Apr 2012
- Last updated
- 16 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Functional Neuroimaging of Alcoholism Vulnerability: Glutamate, Reward, Impulsivity and Pavlovian-to-Instrumental Transfer (PIT)
- ClinicalTrials.gov ID
- NCT01585168
- Acronym / sponsor ID
- CTNA / 1106008650
- Conditions
- Healthy
- Keywords
- Reward Circuitry, Impulsivity, Family History of Alcoholism, NMDA/DA Interactions
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 71 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- Dec 2011
- Primary completion
- May 2016 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 25 Apr 2012 (estimated)
- Results
- Posted 25 May 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This project compares Family History Positive (FHP) for alcoholism subjects to matched Family History Negative (FHN) subjects derived from the project Principal Investigator's National Institute on Alcohol Abuse and Alcoholism-funded longitudinal study of drinking behavior in a 2000 college freshman population (known as the Brain and Alcohol Research in College Students study (BARCS)). The age of these subjects is a valuable one at which to capture the transition from harmful use to abuse/dependence. This project explores the effects of memantine in a double-blind, randomized, counterbalanced manner on alcoholism risk-relevant tasks. More specifically, this project studies functional MRI tasks related to different aspects of reward and/or impulsivity-related behavior in different contexts, compares the underlying neural circuitry across tasks, and uses a pharmacologic probe of the glutamatergic system to examine NMDA/DA interactions. The combined measures provide the opportunity to advance our understanding of specific aspects of brain function related to familial alcoholism vulnerability in an already well-characterized population as some members evolve into alcohol abuse. In addition to conventional within-task analyses, functional network connectivity and allied approaches will be used to examine brain networks across tasks.
The investigators will study adult male and female subjects in equal numbers who are either offspring of an alcoholic parent or are FHN matched controls. The investigators will recruit and assess a total of 84 (42 FHP and 42 matched FHN) subjects between the ages of 18-21 years on initial BARCS contact. The investigators will use 4 cognitive tasks during the functional MRI (fMRI) which include: 1) a Monetary Incentive Delay Task that distinguishes networks engaged in motivational (anticipation) and consummatory (outcome) components of reward processing; 2) a Go/No-Go Task that measures the ability to inhibit response to a pre-potent stimulus; 3) an Alcohol Cue Reactivity Task that examines Nucleus Accumbens response to alcohol-related versus matched soft drink stimuli; and 4) a Pavlovian-to-Instrumental Transfer (PIT) Task that dissects a component of the Monetary Incentive Delay (MID) Task, and provides an imaging assay of a transfer-like process that can be related to real-world drinking behavior, thus informing upon and extending the key findings from CTNA-2.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, care provider)
- Number of arms
- 4
- Model description
- All subjects received both the study drug and placebo. Family history was the main variable of interest, and randomization was stratified by this variable.
| Arm | Type | Receives |
|---|---|---|
| Family history positive, Memantine first, then placebo | Experimental | Drug: Memantine, Drug: PlaceboMemantine is a low-side-effect NMDA receptor antagonist usually administered therapeutically to elderly persons with moderately severe Alzheimer's disease in typical doses of 10-20 mg daily. In this study, single doses of 40 mg are administered. |
| Family history positive, placebo first, then Memantine | Placebo comparator | Drug: Memantine, Drug: PlaceboMemantine is a low-side-effect NMDA receptor antagonist usually administered therapeutically to elderly persons with moderately severe Alzheimer's disease in typical doses of 10-20 mg daily. In this study, single doses of 40 mg are administered. |
| Family history negative, Memantine first, then placebo | Experimental | Drug: Memantine, Drug: PlaceboMemantine is a low-side-effect NMDA receptor antagonist usually administered therapeutically to elderly persons with moderately severe Alzheimer's disease in typical doses of 10-20 mg daily. In this study, single doses of 40 mg are administered. |
| Family history negative, placebo first, then Memantine | Placebo comparator | Drug: Memantine, Drug: PlaceboMemantine is a low-side-effect NMDA receptor antagonist usually administered therapeutically to elderly persons with moderately severe Alzheimer's disease in typical doses of 10-20 mg daily. In this study, single doses of 40 mg are administered. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Biological father with a history of Alcoholism
- A least 1 other first- or second-degree relative with a history of Alcoholism.
Key exclusion criteria (13 listed)
- Cannot be an only child
- A diagnosis of DSM-IV-TR Axis I psychotic disorders screened with the Mini International Neuropsychiatric Interview (MINI), done in the BARCS study (with the exception of Alcohol Abuse)
- Report of psychotic disorder in a 1º relative
- Prenatal exposure to alcohol (mother reported to drink 3 or more drinks on an occasion or more than 3 times per month during pregnancy
- Not speaking English fluently or being a non-native English speaker, or being educated in a primary language other than English >grade 1
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 |
|---|---|---|
| MemantineMemantine is a low-side-effect NMDA receptor antagonist usually administered therapeutically to elderly persons with moderately severe Alzheimer's disease in typical doses of 10-20 mg daily. In this study, single doses of 40 mg are administered. | Drug | Family history negative, Memantine first, then placebo, Family history negative, placebo first, then Memantine, Family history positive, Memantine first, then placebo, Family history positive, placebo first, then Memantine |
| PlaceboIdentically appearing sugar pill, given orally | Drug | Family history negative, Memantine first, then placebo, Family history negative, placebo first, then Memantine, Family history positive, Memantine first, then placebo, Family history positive, placebo first, then Memantine |
Primary outcome
Change in Blood Oxygenation Level Dependent (BOLD) Activation in the Amygdala During "Win" Monetary Incentive Delay (MID) Task Between Placebo and Study Medication
Time frame: 4 hours post intervention on each study day, separated by 1 week to 1 month
All participants completed the fMRI Monetary Incentive Delay task on each study day. During the task, participants needed to select the correct response during "win" and "lose" conditions by pressing a button on a button box in the MRI. Participant's BOLD activation response (A measurement of oxygen level that is released to neurons since areas of the brain that are thought to be more "active" or involved in certain tasks require more oxygen to perform the tasks.) was measured while they performed the task in MRI scanner.
Change in Blood Oxygenation Level Dependent (BOLD) Activation in Anterior Cingulate Cortex During "Loss" Condition of Monetary Incentive Delay (MID) Task Between Placebo and Study Medication
Time frame: 4 hours post intervention on each study day, separated by 1 week to 1 month
All participants completed the fMRI Monetary Incentive Delay task on each study day. During the task, participants needed to select the correct response during "win" and "lose" conditions by pressing a button on a button box in the MRI. Participant's BOLD activation response (A measurement of oxygen level that is released to neurons since areas of the brain that are thought to be more "active" or involved in certain tasks require more oxygen to perform the tasks.) was measured while they performed the task in MRI scanner.
2 secondary outcomes
Change in Impulsive Behavior as Measured on the Balloon Analog Risk Task (BART) Computerized Task Between Placebo and Study Medication
Time frame: 3 hours post intervention on each study day, separated by 1 week to 1 month
Change in Impulsive Behavior as Measured on the Experimental Discounting Delay (EDT) Computerized Task Between Placebo and Study Medication
Time frame: 3 hours post intervention on each study day, separated by 1 week to 1 month
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Godfrey D Pearlson, MD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Memantine in people with Healthy, run by Yale University 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 13 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 16 Mar 2021. 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. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 May 2018). 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?
Change in Blood Oxygenation Level Dependent (BOLD) Activation in the Amygdala During "Win" Monetary Incentive Delay (MID) Task Between Placebo and Study Medication (time frame: 4 hours post intervention on each study day, separated by 1 week to 1 month). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Mar 2021.