Alcohol Use Disorder, Couples
Conditions
Keywords
Couple, Alcohol, Therapy
Brief summary
Alcohol Behavioral Couples Therapy (ABCT) is a manualized 12-session, weekly psychosocial intervention that simultaneously reduces alcohol use disorder (AUD) severity and improves relationship functioning. However, there remains room to improve ABCT outcomes. A growing literature suggests that intranasal oxytocin is a medication that holds promise to achieve that goal. Oxytocin has demonstrated the ability to increase prosocial behavior (e.g., trust, safety, social cognition) and restore sensitivity to natural rewards such as interpersonal relationships that are commonly eroded in the context of addiction. Oxytocin has also demonstrated the ability to reduce substance use behaviors (e.g., craving, self-administration, tolerance, withdrawal), and improves the neurobiological foundations of AUD. The primary objective of this Stage II study is to test the efficacy of oxytocin versus placebo in improving (1) AUD symptom severity, (2) relationship functioning, and (3) corticolimbic connectivity among couples receiving ABCT therapy.
Interventions
DRUGOxytocin
A 40-IU dose of oxytocin will be self-administered 30 minutes prior to the start of each weekly ABCT session.
OTHERPlacebo
A placebo will be self-administered 30 minutes prior to the start of each weekly ABCT session.
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double Blind
Intervention model description
Oxytocin and Therapy Placebo and Therapy
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female; any race or ethnicity; aged 18-75 years. 2. Able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of the assessment instruments (\> 26 on the Mini-Mental State Exam). 3. Married, cohabiting, or in a committed relationship for ≥ 6 months. 4. Identified Patients (IPs) must meet Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria for current alcohol use disorder. Couples in which both partners meet diagnostic criteria for current Alcohol Use Disorder (AUD) are eligible for participation. 5. Concurrent substance use disorders (e.g., marijuana) are acceptable provided that alcohol is the IP's primary substance of choice. 6. Participants taking psychotropic medications will be required to be maintained on a stable dose for at least four weeks before study initiation. This is because initiation or change of psychotropic medications during the course of the trial may interfere with interpretation of results.
Exclusion criteria
1. Meeting DSM-5 criteria for a history of or current psychotic or bipolar affective disorders, or with current suicidal or homicidal ideation and intent. Those individuals will be referred clinically for treatment. 2. Participants who present a serious suicide risk or are likely to require hospitalization during the study. 3. Participants on psychotropic medications which have been initiated during the past 4 weeks. They may be re-assessed after at least four weeks on a stable dose. 4. Acute alcohol withdrawal as indicated by Clinical Institute Withdrawal Assessment Alcohol Scale Revised (CIWA-Ar) scores \>8. They may be re-assessed once they are no longer in withdrawal. Those individuals will be referred for medically supervised detoxification. 5. Severe unilateral intimate partner violence in the past 6 months as defined by the Revised Conflict Tactics Scale (CTS-2). 6. Pregnancy or breastfeeding for women. 7. Individuals with implanted metal devices above the waist will be eligible to enroll in the clinical trial but will not be eligible to participate in the neuroimaging component of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Percent Days Abstinent - Measured by Time Line Follow Back (TLFB) | Baseline to week 12 | Change in percent days abstinent was measured by the Time Line Follow Back (TLFB), a semi-structured clinical interview that uses calendar prompts to stimulate recall of alcohol consumption. Percent days abstinent (days with no alcohol consumption) were measured at baseline (60 days prior to study entry) and weekly for 12 weeks (end of treatment phase), with lower percentage of drinking days representing better outcomes. Time Line Follow Back (TLFB), a clinician assessed measure, will be used to report percent days abstinent (days with no alcohol consumption) and percent days heavy drinking (5 or more days of binge drinking per month). |
| Change in Relationship Functioning - Measured by Dyadic Adjustment Scale - Short Form (DAS-7) | Baseline to week 12 | Change in relationship functioning was measured by the Dyadic Adjustment Scale - Short Form (DAS-7), 7-item Likert-type self-report measure assessing four relationship domains (satisfaction, intimacy, affective expression, and agreement). The DAS-7 was administered at baseline and weekly for 12 weeks (end of treatment). Scores range from 0-36, with higher scores representing better relationship functioning. |
| Change in Percent Days Heavy Drinking - Measured by Time Line Follow Back (TLFB) | Baseline to week 12 | Change in percent days abstinent was measured by the Time Line Follow Back (TLFB), a semi-structured clinical interview that uses calendar prompts to stimulate recall of alcohol consumption. Percent heavy drinking days defined in a sex-specific manner (\> 4 standard drinks for women or \> 5 for men) were measured at baseline (60 days prior to study entry) and weekly for 12 weeks (end of treatment phase), with lower percentage of heavy drinking days representing better outcomes. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited through internet advertisements, clinician referrals, and flyers. Following preliminary eligibility screening, Identified Patients and partners completed private written informed and a baseline assessment separately for privacy. The baseline assessment included a history and physical (H&P) exam and a battery of standardized self-report and interview measures. Recruitment and enrollment occurred from May 2019 to April 2023.
Pre-assignment details
Participants were 96 adult romantic couples (total N=192) where at least one partner met diagnostic criteria for Alcohol Use Disorder in the past 6 months.Couples were required to have been in their current relationship for at least 6 months. Participants who were taking psychotropic medications were required to be on a stable dose for 4 weeks before enrolling.
Participants by arm
| Arm | Count |
|---|---|
| Oxytocin A 40-International Unit (IU) dose of oxytocin self-administered 30 minutes prior to the start of each weekly Alcohol Behavioral Couples Therapy (ABCT) session.
All participants assigned to12 weekly, 90-minute therapy sessions delivered by trained Masters or Doctoral-level clinicians consistent with the published manual. | 98 |
| Placebo A placebo self-administered 30 minutes prior to the start of each weekly Alcohol Behavioral Couples Therapy (ABCT) session.
All participants assigned to 12 weekly, 90-minute therapy therapy sessions delivered by trained Masters or Doctoral-level clinicians consistent with the published manual. | 94 |
| Total | 192 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Completed Follow Up Phase (6-month) | Lost to Follow-up | 6 | 1 |
| Treatment Phase | Lost to Follow-up | 6 | 2 |
| Treatment Phase | Opted out of intervention but completed assessments | 5 | 3 |
| Treatment Phase | Withdrawal by Subject | 9 | 11 |
Baseline characteristics
| Characteristic | Oxytocin | Placebo | Total |
|---|---|---|---|
| Age, Continuous Identified Patient | 38.9 years STANDARD_DEVIATION 11.8 | 43.3 years STANDARD_DEVIATION 12.6 | 41.1 years STANDARD_DEVIATION 12.2 |
| Age, Continuous Partner | 38.6 years STANDARD_DEVIATION 13.5 | 42.1 years STANDARD_DEVIATION 12 | 40.35 years STANDARD_DEVIATION 12.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 7 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 94 Participants | 87 Participants | 181 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Identified Patient American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Identified Patient Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Identified Patient Black or African American | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Identified Patient More than one race | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Identified Patient Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Identified Patient Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Identified Patient White | 44 Participants | 43 Participants | 87 Participants |
| Race (NIH/OMB) Partner American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Partner Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Partner Black or African American | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Partner More than one race | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) Partner Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Partner Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Partner White | 45 Participants | 41 Participants | 86 Participants |
| Sex: Female, Male Identified Patient Female | 12 Participants | 14 Participants | 26 Participants |
| Sex: Female, Male Identified Patient Male | 37 Participants | 33 Participants | 70 Participants |
| Sex: Female, Male Partner Female | 38 Participants | 34 Participants | 72 Participants |
| Sex: Female, Male Partner Male | 11 Participants | 13 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 98 | 0 / 94 |
| other Total, other adverse events | 49 / 98 | 38 / 94 |
| serious Total, serious adverse events | 2 / 98 | 6 / 94 |
Outcome results
Primary
Change in Percent Days Abstinent - Measured by Time Line Follow Back (TLFB)
Change in percent days abstinent was measured by the Time Line Follow Back (TLFB), a semi-structured clinical interview that uses calendar prompts to stimulate recall of alcohol consumption. Percent days abstinent (days with no alcohol consumption) were measured at baseline (60 days prior to study entry) and weekly for 12 weeks (end of treatment phase), with lower percentage of drinking days representing better outcomes. Time Line Follow Back (TLFB), a clinician assessed measure, will be used to report percent days abstinent (days with no alcohol consumption) and percent days heavy drinking (5 or more days of binge drinking per month).
Time frame: Baseline to week 12
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Oxytocin | Change in Percent Days Abstinent - Measured by Time Line Follow Back (TLFB) | 36.8 percentage of days abstinent for alcohol |
| Placebo | Change in Percent Days Abstinent - Measured by Time Line Follow Back (TLFB) | 35.9 percentage of days abstinent for alcohol |
Primary
Change in Percent Days Heavy Drinking - Measured by Time Line Follow Back (TLFB)
Change in percent days abstinent was measured by the Time Line Follow Back (TLFB), a semi-structured clinical interview that uses calendar prompts to stimulate recall of alcohol consumption. Percent heavy drinking days defined in a sex-specific manner (\> 4 standard drinks for women or \> 5 for men) were measured at baseline (60 days prior to study entry) and weekly for 12 weeks (end of treatment phase), with lower percentage of heavy drinking days representing better outcomes.
Time frame: Baseline to week 12
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Oxytocin | Change in Percent Days Heavy Drinking - Measured by Time Line Follow Back (TLFB) | 11.8 percentage of heavy drinking days |
| Placebo | Change in Percent Days Heavy Drinking - Measured by Time Line Follow Back (TLFB) | 9.9 percentage of heavy drinking days |
Primary
Change in Relationship Functioning - Measured by Dyadic Adjustment Scale - Short Form (DAS-7)
Change in relationship functioning was measured by the Dyadic Adjustment Scale - Short Form (DAS-7), 7-item Likert-type self-report measure assessing four relationship domains (satisfaction, intimacy, affective expression, and agreement). The DAS-7 was administered at baseline and weekly for 12 weeks (end of treatment). Scores range from 0-36, with higher scores representing better relationship functioning.
Time frame: Baseline to week 12
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Oxytocin | Change in Relationship Functioning - Measured by Dyadic Adjustment Scale - Short Form (DAS-7) | 25.0 score on a scale |
| Placebo | Change in Relationship Functioning - Measured by Dyadic Adjustment Scale - Short Form (DAS-7) | 25.0 score on a scale |
Post Hoc
Change in Alcohol Problem Severity - Measured by Alcohol Use Disorder Identification Test (AUDIT)
Change in alcohol problem severity was measured by the Alcohol Use Disorder Identification Test (AUDIT), a 10-item Likert-type self-report measure. The AUDIT was administered at baseline and weekly for 12 weeks (end of treatment). Scores range from 0 to 40, with scores of 15 or greater representing moderate to severe Alcohol Use Disorder (AUD).
Time frame: Baseline to week 12
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Oxytocin | Change in Alcohol Problem Severity - Measured by Alcohol Use Disorder Identification Test (AUDIT) | 14.6 score on a scale |
| Placebo | Change in Alcohol Problem Severity - Measured by Alcohol Use Disorder Identification Test (AUDIT) | 13.1 score on a scale |
Post Hoc
Changes in Patient Outcomes Based on Partners' Alcohol Use Disorder (AUD) Status - Measured by Alcohol Use Disorder Identification Test (AUDIT)
Between-group differences in patients' outcomes based on partners' alcohol use disorder (AUD) status measured by the Alcohol Use Disorder Identification Test (AUDIT), a 10-item Likert-type self-report measure. Scores range from 0-40 on the AUDIT, with higher scores representing greater problems with alcohol use, and 15 or greater representing AUD. Group differences in patient outcomes included percent days abstinent and percent days heaving drinking, measured by the Time Line Follow Back (TLFB), a semi-structured clinical interview. Outcomes also included patients' relationship functioning, measured by the Dyadic Adjustment Scale-Short Form (DAS-7), a 7-item Likert-type self-report measure, and patients' alcohol problem severity, measured by the AUDIT, a 10-item Likert-type self-report measure. DAS score ranges from 0 to 36, with a higher score indicating more positive relationship quality. Scores less than 21 are considered to indicate a relationship in distress.
Time frame: Baseline to week 12
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oxytocin | Changes in Patient Outcomes Based on Partners' Alcohol Use Disorder (AUD) Status - Measured by Alcohol Use Disorder Identification Test (AUDIT) | Percent days abstinent | -0.03 Cohen's D |
| Oxytocin | Changes in Patient Outcomes Based on Partners' Alcohol Use Disorder (AUD) Status - Measured by Alcohol Use Disorder Identification Test (AUDIT) | Percent heavy drinking days | -0.13 Cohen's D |
| Oxytocin | Changes in Patient Outcomes Based on Partners' Alcohol Use Disorder (AUD) Status - Measured by Alcohol Use Disorder Identification Test (AUDIT) | Relationship functioning | -0.04 Cohen's D |
| Oxytocin | Changes in Patient Outcomes Based on Partners' Alcohol Use Disorder (AUD) Status - Measured by Alcohol Use Disorder Identification Test (AUDIT) | Alcohol problem severity | -0.12 Cohen's D |
| Placebo | Changes in Patient Outcomes Based on Partners' Alcohol Use Disorder (AUD) Status - Measured by Alcohol Use Disorder Identification Test (AUDIT) | Alcohol problem severity | -0.26 Cohen's D |
| Placebo | Changes in Patient Outcomes Based on Partners' Alcohol Use Disorder (AUD) Status - Measured by Alcohol Use Disorder Identification Test (AUDIT) | Percent days abstinent | 0.00 Cohen's D |
| Placebo | Changes in Patient Outcomes Based on Partners' Alcohol Use Disorder (AUD) Status - Measured by Alcohol Use Disorder Identification Test (AUDIT) | Relationship functioning | 0.01 Cohen's D |
| Placebo | Changes in Patient Outcomes Based on Partners' Alcohol Use Disorder (AUD) Status - Measured by Alcohol Use Disorder Identification Test (AUDIT) | Percent heavy drinking days | -0.39 Cohen's D |