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Functional Neuroimaging of Alcoholism Vulnerability (PIT) (CTNA)

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ClinicalTrials.gov Identifier: NCT01585168
Recruitment Status : Completed
First Posted : April 25, 2012
Results First Posted : May 25, 2018
Last Update Posted : May 25, 2018
Sponsor:
Information provided by (Responsible Party):
Yale University

Tracking Information
First Submitted Date  ICMJE April 23, 2012
First Posted Date  ICMJE April 25, 2012
Results First Submitted Date  ICMJE November 3, 2017
Results First Posted Date  ICMJE May 25, 2018
Last Update Posted Date May 25, 2018
Study Start Date  ICMJE December 2011
Actual Primary Completion Date May 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 26, 2018)
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 24, 2012)
MID Task [ Time Frame: 48 months ]
The primary outcome is change in nucleus accumbens BOLD activation during the monetary incentive delay task.
Change History Complete list of historical versions of study NCT01585168 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 26, 2018)
  • 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 ]
    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.
  • 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 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 24, 2012)
Impulsivity [ Time Frame: 48 months ]
The secondary outcome is change in impulsive behavior as measured on the delay discounting task (EDT) and BART computerized tasks at Olin.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Functional Neuroimaging of Alcoholism Vulnerability (PIT)
Official Title  ICMJE Functional Neuroimaging of Alcoholism Vulnerability: Glutamate, Reward, Impulsivity and Pavlovian-to-Instrumental Transfer (PIT)
Brief 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 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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention 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 (Participant, Care Provider)
Primary Purpose: Treatment
Condition  ICMJE Healthy
Intervention  ICMJE
  • Drug: Memantine
    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.
  • Drug: Placebo
    Identically appearing sugar pill, given orally
Study Arms  ICMJE
  • Experimental: Family history positive, Memantine first, then placebo
    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.
    Interventions:
    • Drug: Memantine
    • Drug: Placebo
  • Placebo Comparator: Family history positive, placebo first, then Memantine
    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.
    Interventions:
    • Drug: Memantine
    • Drug: Placebo
  • Experimental: Family history negative, Memantine first, then placebo
    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.
    Interventions:
    • Drug: Memantine
    • Drug: Placebo
  • Placebo Comparator: Family history negative, placebo first, then Memantine
    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.
    Interventions:
    • Drug: Memantine
    • Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 26, 2018)
71
Original Estimated Enrollment  ICMJE
 (submitted: April 24, 2012)
84
Actual Study Completion Date  ICMJE May 2016
Actual Primary Completion Date May 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Biological father with a history of Alcoholism
  • A least 1 other first- or second-degree relative with a history of Alcoholism.

Exclusion Criteria:

  • 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)
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 35 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01585168
Other Study ID Numbers  ICMJE 1106008650
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Yale University
Study Sponsor  ICMJE Yale University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Godfrey D Pearlson, MD Yale University
PRS Account Yale University
Verification Date April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP