Functional Neuroimaging of Alcoholism Vulnerability (PIT)

NCT01585168 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 1106008650
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

Reward Circuitry; Impulsivity; Family History of Alcoholism; NMDA/DA Interactions

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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

  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

  3 hours post intervention on each study day, separated by 1 week to 1 month

Study Arms (4)

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.

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.

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.

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.

Drug: Memantine; Drug: Placebo

Interventions

Memantine DRUG

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.

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

Placebo DRUG

Identically appearing sugar pill, given orally

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

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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)
• Inability to comprehend the consent form appropriately
• Female participants under 125 pounds will be excluded from participating due to the strength and side effects in this segment of the population.

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

Olin Neuropsychiatry Research Center at the Institute of Living, Hartford Hospital

Hartford, Connecticut, 06106, United States

Location

MeSH Terms

Conditions

Impulsive Behavior

Interventions

Memantine

Condition Hierarchy (Ancestors)

Behavior

Intervention Hierarchy (Ancestors)

Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Dr. Godfrey Pearlson
• Organization: Yale University

Godfrey.Pearlson@hhchealth.org

(860) 545-7757

Study Officials

• Godfrey D Pearlson, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: All subjects received both the study drug and placebo. Family history was the main variable of interest, and randomization was stratified by this variable.

Study Record Dates

• First Submitted: April 23, 2012
• First Posted: April 25, 2012
• Study Start: December 1, 2011
• Primary Completion: May 1, 2016
• Study Completion: May 1, 2016
• Last Updated: March 16, 2021
• Results First Posted: May 25, 2018

Record last verified: 2021-02

Locations

US (1)