Functional Neuroimaging of Alcoholism Vulnerability (PIT) (CTNA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2012 by Yale University
Sponsor:
Information provided by (Responsible Party):
Yale University
ClinicalTrials.gov Identifier:
NCT01585168
First received: April 23, 2012
Last updated: May 2, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention
Healthy
Drug: Memantine
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Basic Science
Official Title: Functional Neuroimaging of Alcoholism Vulnerability: Glutamate, Reward, Impulsivity and Pavlovian-to-Instrumental Transfer (PIT)

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Monetary Incentive Delay (MID) Task [ Time Frame: 48 months ] [ Designated as safety issue: No ]
    The primary outcome is change in nucleus accumbens Blood Oxygenation Level Dependent (BOLD) activation during the MID task.


Secondary Outcome Measures:
  • Impulsivity [ Time Frame: 48 months ] [ Designated as safety issue: No ]
    The secondary outcome is change in impulsive behavior as measured on the Experimental Discounting Delay (EDT) task and Balloon Analog Risk Task (BART) computerized tasks at Olin.


Estimated Enrollment: 84
Study Start Date: December 2011
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
Placebo Comparator: Sugar Pill 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.

  Eligibility

Ages Eligible for Study:   18 Years to 25 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01585168

Contacts
Contact: Godfrey Pearlson, MD 860-545-7757 godfrey.pearlson@yale.edu
Contact: Karen Anderson, RN 860-545-7767 kxander@harthosp.org

Locations
United States, Connecticut
Olin Neuropsychiatry Research Center at the Institute of Living, Hartford Hospital Recruiting
Hartford, Connecticut, United States, 06106
Contact: Godfrey D Pearlson, MD    860-545-7757    godfrey.pealrson@yale.edu   
Contact: Karen Anderson, RN    860-545-7767    kxander@harthosp.org   
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Godfrey D Pearlson, MD Yale University
  More Information

No publications provided

Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT01585168     History of Changes
Other Study ID Numbers: 1106008650
Study First Received: April 23, 2012
Last Updated: May 2, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Yale University:
Reward Circuitry
Impulsivity
Family History of Alcoholism
NMDA/DA Interactions

Additional relevant MeSH terms:
Alcoholism
Alcohol-Related Disorders
Substance-Related Disorders
Mental Disorders
Memantine
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 20, 2014