Multimodal Neuroimaging of Stress and Reward Cues to Assess Alcoholism Risk and Relapse

Extending previous findings, and applying a novel multi-method translational approach, this project hypothesizes that there are alcohol-related neuroendocrine and neural changes observable in acute and protracted abstinence, and which can accurately classify future relapse and treatment outcome in separate alcohol dependent (AD) patient samples, thereby validating them as biomarkers of relapse, with potential clinical utility as prognostic markers in identifying and treating those most susceptible to relapse.

Study Overview

• Status: Completed
• Conditions: Alcohol Dependence
• Intervention / Treatment: Device: Multi-method Neuroendocrine and Neuroimaging Procedure Scan 1; Device: Multi-method Neuroendocrine and Neuroimaging Procedure Scan 2

• Study Type: Interventional
• Enrollment (Actual): 224
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale Stress Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male and females, aged 18-60 years;
• Good health as verified by screening examination;
• Able to read English and complete study evaluations;
• Able to provide informed written and verbal consent;
• AD sample must meet DSM-5 criteria for AUD as assessed using SCID-I and have positive alcohol urine toxicology screens on admission to study; while HC group must never have met criteria for AUD, with non-binging and nonhazardous alcohol intake levels( men: below15 drinks/week; women: less than 8 drinks/week); and with negative alcohol urine toxicology screens; Page

Exclusion Criteria:

• Meet current criteria for dependence on another psychoactive substance, excluding nicotine; (ii) Current use of opiates or past history of opiate abuse/dependence;
• Regular use of anticonvulsants, sedatives/hypnotics, prescription analgesics, other antihypertensives, anti-arrhythmics, antiretroviral medications, SSRI's naltrexone, antabuse;
• Psychotic or otherwise severely psychiatrically disabled (i.e., suicidal, homicidal, current mania);
• Significant underlying medical conditions such as a history of seizure disorder, cerebral, renal, thyroid or cardiac pathology which in the opinion of study physician would preclude subjects from fully cooperating or be of potential harm during the course of the study;
• Any psychotic disorder or current Axis I psychiatric symptoms (excluding anxiety disorders) requiring specific attention, including need for psychiatric medications;
• hypotensive individuals with sitting blood pressure below 90/50 mmHG;
• Women who are pregnant, nursing or refuse to use a reliable form of birth control (as assessed by pregnancy tests during initial medical evaluation, and assessed every two weeks during the course of the study); and
• those with metal in their body excluded from MRI due to safety.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Seeking Alcohol Dependent Adults; Group consists of 100 treatment seeking alcohol dependent (AD) men and women (ages 18-60). AD subjects will complete either 8 weeks of outpatient treatment at the Yale Stress Center, or the first 4 weeks as inpatient treatment at the CNRU, followed by 4 weeks of outpatient treatment at the Yale Stress Center. While in outpatient treatment, AD subjects may be admitted to the CNRU or HRU for the 1-5 days prior to one or both of their scans, to ensure abstinence for their scans.	Device: Multi-method Neuroendocrine and Neuroimaging Procedure Scan 1; The MRI scan will be conducted on a 3-T Siemens Trio MRI system equipped with a standard quadrature head coil, using T1 MPRAGE sequence for structural scanning and T2*-sensitive gradient-recalled single shot echo planar pulse sequence for functional scans. Two multimethod MRI scans will be conducted in the AD sample, while the controls will participate in a single scan.; Device: Multi-method Neuroendocrine and Neuroimaging Procedure Scan 2; The MRI scan will be conducted on a 3-T Siemens Trio MRI system equipped with a standard quadrature head coil, using T1 MPRAGE sequence for structural scanning and T2*-sensitive gradient-recalled single shot echo planar pulse sequence for functional scans. Two multimethod MRI scans will be conducted in the AD sample, while the controls will participate in a single scan.
Active Comparator: Social Drinking Controls; Group consists of demographically and handedness matched 50 socially drinking controls. Healthy controls will be moderate and binge/heavy social drinkers who will participate in a single MRI session after baseline assessments. Healthy controls may be admitted to the HRU overnight prior to their scan.	Device: Multi-method Neuroendocrine and Neuroimaging Procedure Scan 1; The MRI scan will be conducted on a 3-T Siemens Trio MRI system equipped with a standard quadrature head coil, using T1 MPRAGE sequence for structural scanning and T2*-sensitive gradient-recalled single shot echo planar pulse sequence for functional scans. Two multimethod MRI scans will be conducted in the AD sample, while the controls will participate in a single scan.
Active Comparator: Prazosin/Placebo Group; This is a separate group of 60 treatment seeking AD subjects in a NIAAA-funded RCT of Prazosin vs placebo for alcohol dependence ( PI: Sinha, Hic protocol 0705002691, NCT00585780) to assess target primary and secondary predictors of alcohol treatment outcomes in the context of a currently ongoing RCT. AD subjects enrolled in the PZ/PL RCT will NOT be given drugs as part of this study. That study and intervention is listed elsewhere (NCT00585780). Subjects will participate in a baseline scan and a second scan between weeks 10-12 of the 12-week RCT with follow-ups. PZ/PL is only given to subjects enrolled in 0705002691, not the current protocol.	Device: Multi-method Neuroendocrine and Neuroimaging Procedure Scan 1; The MRI scan will be conducted on a 3-T Siemens Trio MRI system equipped with a standard quadrature head coil, using T1 MPRAGE sequence for structural scanning and T2*-sensitive gradient-recalled single shot echo planar pulse sequence for functional scans. Two multimethod MRI scans will be conducted in the AD sample, while the controls will participate in a single scan.; Device: Multi-method Neuroendocrine and Neuroimaging Procedure Scan 2; The MRI scan will be conducted on a 3-T Siemens Trio MRI system equipped with a standard quadrature head coil, using T1 MPRAGE sequence for structural scanning and T2*-sensitive gradient-recalled single shot echo planar pulse sequence for functional scans. Two multimethod MRI scans will be conducted in the AD sample, while the controls will participate in a single scan.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Relapse	The Time-Line Follow-Back Interview will be used to assess alcohol use in the previous ninety days, during the study and during follow-up until relapse occurs or 200 days is up.	Up to 200 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to heavy drinking relapse	The Time-Line Follow-Back Interview will be used to assess alcohol use in the previous ninety days (this is standard for TLFB surveys), during the study and during follow-up until relapse occurs or 200 days is up.	Up to 200 days
Percent of days of alcohol use in follow-up	The Time-Line Follow-Back Interview will be used to assess alcohol use in the previous ninety days (which is standard for TLFB surveys), during the study and during follow-up. This can only be measured once relapse occurs. It will be measured once relapse occurs or will not be measured at all if relapse does not occur within 200 days.	Up to 200 days

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2015
• Primary Completion (Actual): June 30, 2022
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: November 16, 2015
• First Submitted That Met QC Criteria: November 24, 2015
• First Posted (Estimate): November 26, 2015

Study Record Updates

• Last Update Posted (Actual): April 18, 2023
• Last Update Submitted That Met QC Criteria: April 13, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Alcoholism
• Other Study ID Numbers: 1501015225; 2R01AA013892-11 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No