Clinical trial NCT06030154: Amplification of Positivity for Alcohol Use
Official title: Developing and Evaluating a Positive Valence Treatment for Alcohol Use Disorder With Anxiety or Depression
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Alcohol Use Disorder
Anxiety
Depression
Lead sponsor: Laureate Institute for Brain Research, Inc.
Sponsor class: OTHER
Collaborators: name: University of California, San Diego
name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
First posted: 2023-09-08
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: Inclusion Criteria:

1. Age between 18 and 65 years old.
2. Meeting diagnostic criteria for alcohol use disorder according to the DSM-5.
3. 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.
4. Below normative levels of positive affect as indexed by PROMIS Positive Affect \<50.
5. Able to provide written informed consent.
6. 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.
3. No telephone or easy access to telephone.
4. Diagnosis of Schizophrenia spectrum, other psychotic disorders, or bipolar I disorder.
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), cocaine, marijuana, opiates, amphetamines, methamphetamines, phencyclidine, benzodiazepines, barbiturates, methadone, and oxycodone 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 or change in the dose or prescription of a medication within the 6 weeks prior to enrolling in the study that could potentially affect brain functioning (e.g., stimulants, anxiolytics, antipsychotics, mood stabilizers, anti-hypertensives). The current use of antidepressants (i.e., SSRIs) will not be excluded as long as the dose has remained consistent for 6 weeks prior to baseline assessment sessions. While individuals reporting use of benzodiazepines will be excluded; individuals with sporadic use (i.e., less than once per week) may be included, but will be asked to refrain from using within 72 hours prior to assessment sessions. 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 baseline assessments conducted by licensed clinicians.
14. Given the current study involves development of the positive affect intervention, special vulnerable populations (pregnant women, fetuses, neonates, prisoners, children) will not be enrolled.

Primary outcomes:
measure: Perceived acceptability and satisfaction of the intervention as measured with the Adherence and Acceptability Scale (AAS)
timeFrame: Average of total scores from the following time points: pre-treatment, 2 weeks after starting treatment, 6 weeks after starting treatment, and at post-treatment (average of 16 weeks after baseline assessment)
measure: Change in positive affect self-report measured with National Institute of Health (NIH) Patient Reported Outcome Measurement and Information System (PROMIS) Positive Affect score
timeFrame: Trajectory of change from pre-treatment to post-treatment (last time point assessed on average 16 weeks after baseline assessment)
measure: Change in number of drinking days in the past month
timeFrame: Trajectory of change from pre-treatment to post-treatment (last time point assessed on average 16 weeks after baseline assessment)
Secondary outcomes:
measure: Distress/Endorsement Validation Scale (DEVS)
timeFrame: Average of total scores from the following time points:2 weeks after starting treatment, post-treatment (average of 16 weeks after baseline assessment)
measure: Change in Average drinks per drinking day
timeFrame: Trajectory of change from pre-treatment to post-treatment (last time point assessed on average 16 weeks after baseline assessment)
measure: Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety Scale
timeFrame: Trajectory of change from pre-treatment to post-treatment (last time point assessed on average 16 weeks after baseline assessment)
measure: Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Depression Scale
timeFrame: Trajectory of change from pre-treatment to post-treatment (last time point assessed on average 16 weeks after baseline assessment)
measure: Change in Sheehan Disability Scale (SDS)
timeFrame: Trajectory of change from pre-treatment to post-treatment (last time point assessed on average 16 weeks after baseline assessment)
measure: Change in the NIH Toolbox Loneliness survey
timeFrame: Trajectory of change from pre-treatment to post-treatment (last time point assessed on average 16 weeks after baseline assessment)
measure: Change in the Patient-Reported Outcomes Measurement Information System (PROMIS) Meaning and Purpose Scale
timeFrame: Trajectory of change from pre-treatment to post-treatment (last time point assessed on average 16 weeks after baseline assessment)
Other outcomes:
Locations:
city: Tulsa
country: United States
facility: Laureate Institute for Brain Research
state: Oklahoma
Study officials:
affiliation: Laureate Institute for Brain Research
name: Robin L Aupperle, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.