Amplification of Positivity for Alcohol Use

NCT ID: NCT06030154

Last Updated: 2025-07-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-25
• Study Completion Date: 2026-07-31

Brief Summary

The proposed study consists of two phases. During Phase 1, the investigators will recruit a small sample of participants to complete a psychosocial intervention termed Amplification of Positivity (AMP) for individuals experiencing comorbid depression or anxiety disorders and alcohol use disorder (AMP-A). These participants will be asked to provide both qualitative and quantitative input about the AMP-A intervention. Based on their input and clinician input, the AMP-A manual will be modified for use in Phase 2. The goal is to recruit up to 20 participants in order to ensure there will be at least 8 participants who complete all sessions of AMP-A. Phase 2 is a randomized clinical trial (RCT) protocol in which individuals experiencing comorbid depression or anxiety disorders and alcohol use disorder will be randomized to complete AMP-A or an evidence-based cognitive-behavioral therapy (CBT) intervention. Up to 100 participants will be recruited in order to reach a target of N=60. Assessed outcomes will include participant acceptability and completion rates, participant compliance with the intervention, positive and negative affect, substance use- and depression and anxiety-related symptom severity, functional disability, and neural reactivity to reward and alcohol cues during functional magnetic resonance imaging (fMRI).

Detailed Description

Substance use disorder, including alcohol use disorder, is characterized by enhanced neural responsivity to drug (alcohol) cues, but reduced neural responsivity to non-drug reward cues. These effects may be exacerbated by comorbid major depressive disorder (MDD) or symptoms of anhedonia, comorbidities which are particularly high amongst alcohol use disorder. Response rates for current interventions with alcohol use disorder are rather poor, with only 58% experiencing benefits greater than control conditions. There is a need to identify interventions that may target reward responsivity in a way that would promote recovery, reduce affective disturbance, and support better long-term functioning for individuals experiencing alcohol use disorder and comorbid depression and anxiety disorders. Positive affect interventions have recently been developed and tested in other populations (i.e., HIV, anxiety/depression) as a way of enhancing positive valence and reward processing. These interventions have shown significant promise in these populations but have yet to be examined in the context of alcohol use disorder.

The current study would test the feasibility and acceptability of a 12-session protocol focused on amplification of positivity with populations experiencing comorbid alcohol use disorder and depression or anxiety disorders and explore the impact of the intervention on positive affect, negative affect, alcohol use and craving, and neural response patterns during reward and drug cue processing. The proposed project would support the final stages of intervention development. First, an initial pilot study will be conducted to obtain qualitative and quantitative input from N=8 participants with Alcohol Use Disorder (AUD) + Anxiety/Depression (ANX/DEP) who are asked to engage in the amplification of positivity for AUD intervention (AMP-A) and their clinicians to inform modifications to the AMP-A manual. Then, a pilot randomized clinical trial (RCT) will be conducted in which N=60 individuals with Alcohol Use Disorder (AUD) + Anxiety/Depression (ANX/DEP) will be randomized to complete the modified AMP-A intervention or a cognitive behavioral therapy (CBT)intervention. Intervention will consist of 12 sessions that may be done virtually or in-person. Participation in both phases will include completion of interview-based and self-report measures at pre-treatment, weekly during treatment, at post-treatment, and at 3-month follow-up.

Conditions

Alcohol Use Disorder; Anxiety; Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Amplification of Positivity Therapy

AMP-A will involve 12, one-hour weekly therapy sessions completed one-on-one with a therapist. The sessions and between-session homework will focus on amplifying positive thoughts, emotions, and behaviors to address anxiety/depression and alcohol use.

Group Type: EXPERIMENTAL

Amplification of Positivity Therapy

Intervention Type: BEHAVIORAL

Amplification of Positivity Therapy

Surveys and Interviews

Intervention Type: BEHAVIORAL

Participants will answer questions regarding their mental and physical health as well as their substance use on the computer and in an interview format.

Cognitive Behavioral Therapy

The CBT intervention will involve 12, one-hour weekly therapy sessions completed one-on-one with a therapist. The sessions and between-session homework will focus on monitoring of the relationship between thoughts, emotions, and alcohol use.

Group Type: ACTIVE_COMPARATOR

Cognitive Behavioral Therapy

Intervention Type: BEHAVIORAL

Cognitive Behavioral Therapy

Surveys and Interviews

Intervention Type: BEHAVIORAL

Participants will answer questions regarding their mental and physical health as well as their substance use on the computer and in an interview format.

Interventions

Cognitive Behavioral Therapy

Cognitive Behavioral Therapy

Intervention Type: BEHAVIORAL

Amplification of Positivity Therapy

Amplification of Positivity Therapy

Intervention Type: BEHAVIORAL

Surveys and Interviews

Participants will answer questions regarding their mental and physical health as well as their substance use on the computer and in an interview format.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

1. Age between 18 and 65 years old.

2. Meeting diagnostic criteria for alcohol use disorder 42 according to the DSM-5.

3. Reports that they would like to seek treatment for AUD and that AUD is one of the primary challenges they would like to address in treatment.

4. Phase 1: Significant depression or anxiety symptoms as indexed by scoring Patient Health Questionnaire (PHQ-9) ≥ 10 and/or Overall Anxiety Severity and Impairment Scale (OASIS) ≥ 8. Phase 2: Significant depression or anxiety symptoms as indexed by scoring ≥ 55 on either of the NIH PROMIS ((Patient-Reported Outcomes Measurement Information System) Depression and/or Anxiety scales.

5. Below normative levels of positive affect as indexed by PROMIS Positive Affect <50.

6. Able to provide written informed consent.

7. Have sufficient proficiency in the English language to understand and complete interviews, questionnaires, and all other study procedures.

Exclusion Criteria

1. Unwillingness or inability to complete any of the major aspects of the study protocol, including self-report or behavioral assessment. However, failing to complete some individual aspects of these assessment sessions will be acceptable (i.e., being unwilling to answer individual items on some questionnaires or being unwilling to complete a behavioral task). In addition, the neuroimaging portion of the protocol will be optional.

2. Non-correctable vision or hearing problems that interfere with the participant's ability to complete study assessments.

3. No telephone or easy access to telephone.

4. Diagnosis of Schizophrenia spectrum, other psychotic disorders, obsessive-compulsive disorder, eating disorders, substance use disorders within the past year other than alcohol use disorder or cannabis use disorder, or bipolar I disorder. Mild binge eating disorder will be considered for inclusion on a case-by-case basis at the discretion of the PI.

5. Active suicidal ideation with plan and intent to attempt suicide within the next month.

6. Has a history of unstable liver or renal insufficiency; glaucoma; significant and unstable cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, or metabolic disturbance; or any other condition that, in the opinion of the investigator, would make participation not be in the best interest (e.g., compromise the well-being) of the subject or that could prevent, limit, or confound the protocol-specified assessments.

7. A positive test for drugs of abuse, including alcohol (breath test) and substances of dependence that are not physician prescribed (i.e., cocaine, cannabis, opioids, stimulants).at the time of baseline assessments. Participants will be asked to refrain from using alcohol within 24 hours prior to assessment sessions and to refrain from using marijuana within 48 hours of assessment sessions.

8. Current use of a medication within the 6 weeks prior to enrolling in the study that could potentially affect brain functioning and/or the positive valence system (e.g., anxiolytics, antipsychotics, mood stabilizers, opioid antagonists such as naltrexone or other medications specifically targeting alcohol use or cravings). The current use of antidepressants (i.e., SSRIs), benzodiazepines, and psychostimulants will not be excluded as long as the dose has remained consistent for 6 weeks prior to baseline assessment sessions. Individuals who are on stable doses (≥ 6 weeks) of mood stabilizers or antipsychotics may be included if it is determined that they are being prescribed for purposes of treating unipolar depression or anxiety. Inclusion of individuals reporting other types of medications or supplements not listed or considered this far will be at the discretion of the PI according to evidence in the literature of it affecting brain function or brain blood flow.

9. Taking drugs that affect the fMRI hemodynamic response (e.g., methylphenidate, acetazolamide, and excessive caffeine intake > 1000 mg/day) - Phase 2 only

10. Concurrent engagement in psychosocial treatments that specifically target alcohol use disorder or mood/anxiety symptoms and began within 12 weeks of baseline assessments. Individuals concurrently receiving psychosocial treatments for other symptoms, or that are not specifically targeting symptoms (e.g., ongoing support groups) will not be excluded as long as the dose of treatment (i.e., frequency of sessions) has not changed significantly within 6 weeks prior to enrolling in the study.

11. MRI contraindications (for those in Phase 2 opting into this portion) including: cardiac pacemaker, metal fragments in eyes/skin/body (shrapnel), aortic/aneurysm clips, prosthesis, by-pass surgery/coronary artery clips, hearing aid, heart valve replacement, shunt (ventricular or spinal), electrodes, metal plates/pins/screws/wires, or neuro/bio-stimulators (TENS unit), persons who have ever been a professional metal worker/welder, history of eye surgery/eyes washed out because of metal, vision problems uncorrectable with lenses, inability to lie still on one's back for 60-120 minutes; prior neurosurgery; tattoos or cosmetic makeup with metal dyes, unwillingness to remove body piercings, and pregnancy - Phase 2 only

12. Moderate to severe traumatic brain injury (>30 min. loss of consciousness or >24 hours posttraumatic amnesia) or other neurocognitive disorder with evidence of neurological deficits, neurological disorders, or severe or unstable medical conditions that might be compromised by participation in the study (to be determined by primary care provider).

13. Severity of alcohol use disorder requiring more intensive treatment (i.e., intensive outpatient or residential), as determined by licensed clinician determination of American Society of Addiction Medicine (ASAM) Criteria ≥ 0-1 across dimensions, with the exception of a '2' on the emotional dimension.

14. Given the current study involves development of the positive affect intervention, we will not enroll any special vulnerable populations (pregnant women, fetuses, neonates, prisoners, children).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, San Diego

OTHER

Sponsor Role: collaborator

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

NIH

Sponsor Role: collaborator

Laureate Institute for Brain Research, Inc.

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robin L Aupperle, PhD

Role: PRINCIPAL_INVESTIGATOR

Laureate Institute for Brain Research

Locations

Laureate Institute for Brain Research

Tulsa, Oklahoma, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Robin L Aupperle, PhD

Role: CONTACT

neurocatt@laureateinstitute.org

918-502-5155

Facility Contacts

Robin L Aupperle, PhD

Role: primary

neurocatt@laureateinstitute.org

918-502-5155

References

Akeman E, White E, Wolitzky-Taylor K, Santiago J, McDermott TJ, DeVille DC, Stewart JL, Paulus M, Taylor CT, Aupperle RL. Amplification of Positivity Therapy for Co-occurring Alcohol Use Disorder with Depression and Anxiety Symptoms: Pilot Feasibility Study and Case Series. Behav Modif. 2022 Sep;46(5):1021-1046. doi: 10.1177/01454455211030506. Epub 2021 Jul 12.

Reference Type: BACKGROUND

PMID: 34253077 (View on PubMed)

Taylor CT, Lyubomirsky S, Stein MB. Upregulating the positive affect system in anxiety and depression: Outcomes of a positive activity intervention. Depress Anxiety. 2017 Mar;34(3):267-280. doi: 10.1002/da.22593. Epub 2017 Jan 6.

Reference Type: BACKGROUND

PMID: 28060463 (View on PubMed)

Kryza-Lacombe M, Pearson N, Lyubomirsky S, Stein MB, Wiggins JL, Taylor CT. Changes in neural reward processing following Amplification of Positivity treatment for depression and anxiety: Preliminary findings from a randomized waitlist controlled trial. Behav Res Ther. 2021 Jul;142:103860. doi: 10.1016/j.brat.2021.103860. Epub 2021 Apr 15.

Reference Type: BACKGROUND

PMID: 33894554 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

R34AA030688

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2022-003

Identifier Type: -

Identifier Source: org_study_id