Sex Differences in the Response to Abstinence From Alcohol. (SPAR)

Indiana University

Status and phase: Enrolling; Phase 1

Conditions: Alcohol Use Disorder

Treatments: Behavioral: Abstinence from alcohol; Behavioral: Usual drinking; Drug: Intravenous Alcohol

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03827460

R01AA027236-05 (U.S. NIH Grant/Contract)

1809467722

Details and patient eligibility

About

In laboratory animals, repeated cycles of abstinence from and return to alcohol drinking can lead to changes in alcohol intake. In a study of the effect of abstinence on drinking in humans, the investigators found evidence that abstinence affects drinking differently in women compared to men. In the present study, the investigators propose to study how men and women respond to abstinence, and whether this information can be used to improve intervention and prevention strategies.

Full description

Women and men differ in how quickly they progress from social to problematic alcohol drinking. In laboratory animals, short-term abstinence increases alcohol consumption, with repeated deprivations leading to disordered drinking. In a preliminary study, the investigators found that men and women differed in how their motivation to drink alcohol changed after a short period of abstinence. The investigators hypothesize that this difference may affect their transition to alcohol use disorders. The objectives of this application are to characterize the human post abstinence response, and use identical alcohol exposures to study the mechanisms underlying identified sex differences. In addition, the investigators will complete a 2 year prospective study of natural drinking patterns to assess how self-reported abstinence intervals influence drinking trajectories. The long-term goal of this project is to inform alcohol use disorder treatment and to design and test novel interventions using the laboratory model of post-abstinence response. There is a critical unfilled need to understand sex differences in disease progression, and this lab-based assessment coupled to longitudinal follow-up provides the rigorous experimental design to begin to meet that need. This project will increase scientific knowledge by advancing the translation between preclinical and clinical models, eventually informing sex-specific intervention and prevention strategies for problematic drinking and establishing a model to test those interventions..

Enrollment: 160 estimated patients

Sex: All

Ages: 21 to 35 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Moderate social drinkers
• Able to understand/complete questionnaires and procedures in English
• Body mass index (BMI) between 18.5 and 32 kg/m2
• Have venous access sufficient to allow blood sampling

Exclusion criteria

• Pregnant or breast-feeding women, or women who intend to become pregnant
• Do not attest to using accepted forms of birth control for the infusion phase of the study
• Current treatment for, or desire to be treated for, any substance use disorder or court ordered to not drink alcohol
• History of significant adverse reaction to alcohol
• Medical disorders or other conditions such as alcohol withdrawal seizures or delirium tremens that may influence study outcome or participant safety
• Medications (past 30 days) that could influence data or participant safety (e.g. antidepressants, antipsychotics, benzodiazepines, etc.) as determined by investigators
• DSM 5 Disorders (non AUD) or current/history of neurological disease of cerebral origin, or head injury with > 20 min loss of consciousness
• Positive breath alcohol reading on arrival at any study visit
• Actively suicidal (for example, any suicide attempts within the past year or any current suicidal intent, including a plan) or are at serious suicidal risk, by clinical judgment of the investigator
• Any condition for which the principal investigators determine it is unsafe or not prudent to enroll

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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160 participants in 3 patient groups

Free access alcohol self-administration

Experimental group

Description:

During the 2.5-hour free-access self-administration sessions, the participant may choose to complete a task for an alcohol or water reward. Interventions include Abstinence from Alcohol and Usual Drinking

Treatment:

Drug: Intravenous Alcohol

Behavioral: Usual drinking

Behavioral: Abstinence from alcohol

Clamped alcohol exposure

Experimental group

Description:

A battery of behavioral tasks will be administered to participants before, and at the beginning and end of a 3 hour clamped exposure to alcohol (fixed at 80 mg/dL). EEG will be recorded throughout to assess event related potentials associated with task performance. Interventions include Abstinence from Alcohol and Usual Drinking.

Treatment:

Drug: Intravenous Alcohol

Behavioral: Usual drinking

Behavioral: Abstinence from alcohol

2 year followup

No Intervention group

Description:

Participants from both Arm 1 and Arm 2 will be surveyed every 2 months for alcohol consumption for 2 years following the Experimental phase. Interventions include Abstinence from Alcohol and Usual Drinking.