Development of a Novel Transdiagnostic Intervention for Anhedonia - R33 Phase

The overall goal of this project is to develop a novel transdiagnostic treatment for anhedonia, called Behavioral Activation Treatment for Anhedonia (BATA), using ultra-high field functional neuroimaging. There is a critical need for a validated treatment that specifically targets anhedonia, and this project will evaluate the effects of this new treatment on anhedonia and will establish how this treatment impacts brain systems that mediate reward processing, clinical symptoms of anhedonia, functional outcomes, and behavioral indices of reward processing. This work will also identify brain targets by which future novel anhedonia treatment may be evaluated.

Study Overview

• Status: Completed
• Conditions: Anhedonia
• Intervention / Treatment: Behavioral: Behavioral Activation; Behavioral: Mindfulness Treatment

Detailed Description

Deficits in motivation and pleasure, together referred to as anhedonia, are implicated in a number of psychiatric illnesses, including mood and anxiety disorders, substance-use disorders, schizophrenia, and attention-deficit/hyperactivity disorder. As a result, constructs related to anhedonia are central to the NIMH Research Domain Criteria (RDoC) project. Anhedonia is often one of the most difficult psychiatric symptoms to treat and thus represents a critical endophenotype and vulnerability factor for a range of psychiatric disorders. Given the centrality of anhedonia to a large number of psychiatric disorders, improved interventions to treat motivation and pleasure are critical for these disorders. The overall goal of this R61/R33 project is to develop a novel transdiagnostic treatment for anhedonia, called Behavioral Activation Treatment for Anhedonia (BATA). This new intervention is designed to treat anhedonia by emphasizing supported engagement with personally relevant goals and reducing avoidance behaviors. Consistent with the objectives and milestones outlined in RFA-MH-16-406 ("Exploratory Clinical Trials of Novel Interventions for Mental Disorders"), in the R61 phase of this trial that lasted from June 22, 2017-July 31, 2019, the investigators proposed to use an experimental therapeutics approach to first evaluate mesocorticolimbic target engagement by this treatment in a transdiagnostic sample characterized by clinically impairing anhedonia (Aim 1). Specifically, the investigators examined the effects of this treatment, relative to an active comparison treatment, on caudate nucleus activation during reward anticipation and rostral anterior cingulate cortex activation during reward outcomes using ultra-high field (7T) functional magnetic resonance imaging. The investigators also used fMRI to determine the optimal dose of the intervention (Aim 2).

In the current R33 phase of the study, which begins recruitment 8/1/2019, the investigators plan to evaluate the effects of the optimal dose of this new treatment, versus an active comparison treatment, on anhedonic symptoms and functional outcomes (Aim 3), behavioral indicators of reward sensitivity (Aim 4), and neural indicators of reward processing (Aim 5).

• Study Type: Interventional
• Enrollment (Actual): 116
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7255
      • UNC-Chapel Hill School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18-50 years old and treatment seeking;
• SHAPS scores ≥ 20, corresponding to clinically significant anhedonia;
• Clinician's Global Impression Scale-Severity score (CGI-S) > 3 to assure a clinically impaired sample;
• Seeking treatment for anhedonia (i.e., referred from an outpatient clinic or responded to an advertisement for anhedonia treatment; endorses desire for treatment during screening).

Exclusion Criteria:

• Those for whom medication management is the primary gold-standard treatment, including those with bipolar disorder/mania, schizophrenia spectrum, and other psychotic disorders;
• Prior treatment with behavioral activation therapy for depression or mindfulness-based treatments (those with exposure to other forms of psychotherapy, e.g., supportive therapy, will be eligible);
• Those who may have difficulty understanding the cognitive components of BATA, including those with intellectual disability, neurocognitive disorders, and dissociative disorders;
• Feeding and eating disorders which may have confounding effects on the fMRI signal;
• Substance Use Disorders given confounding effects of substances of abuse on the fMRI signal;
• Suicidal intent and plan;
• Psychotropic medication use in the past 4 weeks (8 weeks for fluoxetine) and/or current psychotherapy. Participants must be medication-free at study entry; study personnel will not supervise medication taper for the purpose of the study, but those who taper under the supervision of their regular provider will be eligible;
• Currently pregnant, as measured by urine pregnancy screen immediately before MRI scans;
• Positive urinalysis screen for cocaine, marijuana, opiates, methadone, amphetamines, and benzodiazepines (conducted on-site via Biosite Triage Meter Plus) at study entry.
• No neurological conditions (e.g., history of stroke, seizure, or TBI); Contraindications for fMRI imaging: Metal in the body, dental work that is not fillings or gold, any tattoos, any metal in the body, any metal injury - especially those to the eyes, any other type of implant unless they are 100% plastic.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Behavioral Activation; Treatment will consist of 15 weekly 45-minute sessions. Session 1 provides orientation and psychoeducation on anhedonia, and activity monitoring is introduced. Sessions 2-3 include structured values assessments of 10 life areas to enhance motivation for sustained behavior change and to clarify goals. Following goals clarification, an activity hierarchy is developed, establishing a set of idiographic behavioral targets across life areas prioritized by ease of implementation to scaffold task engagement during the course of treatment.	Behavioral: Behavioral Activation; Treatment will consist of 15 weekly 45-minute sessions.
Active Comparator: Mindfulness Treatment; BATA will be compared to mindfulness based cognitive therapy (MBCT), chosen because its mechanisms of action are hypothesized to impact different brain mechanisms than BATA. Mindfulness is nonjudgmentally bringing awareness and acceptance to one's present-moment experience. MBCT will be administered in an individual format. The MBCT protocol will be modeled on the session outlines presented in Wahbeh et al., 2014. Treatment will be compromised of 15 weekly 45-minute sessions.	Behavioral: Mindfulness Treatment; Treatment will consist of 15 weekly 45-minute sessions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Snaith-Hamilton Pleasure Scale Score Over Time	The Snaith-Hamilton Pleasure Scale (SHAPS), a well-validated 14-item questionnaire will be used to assess hedonic capacity. The sum of the 14 items scores ranges from 0 to 56. A higher score represents more anhedonic symptoms. Treatment duration varied across participants. Participants participated in as few as 8 weekly sessions or in as many as 15 weekly sessions of psychotherapy, based on therapist judgement. Thus the outcome measure timeframe varied between 8 and 15 weeks.	Baseline, Post-treatment (between 8 to 15 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Neural Activation During MID Task Anticipation Phase	Neural activation assessed by Functional Magnetic Resonance Imaging (fMRI) during Monetary Incentive Delay (MID) task. During MID the task, participants respond to "win" trials by pressing a button on a button box in the MRI as quickly as possible when the see a target. MID task reward anticipation is defined by the contrast in fMRI signal between reward and neutral trials during the presentation of cues and the fixation cross. Because this subtraction method is used to define the fMRI signal, it is possible for this value to be negative. Treatment duration varied across participants. Participants participated in as few as 8 weekly sessions or in as many as 15 weekly sessions of psychotherapy, based on therapist judgement. Thus the outcome measure timeframe varied between 8 and 15 weeks.	Baseline, Post-treatment (between 8 to 15 weeks)
Change in Neural Activation During MID Task Outcome Phase	Brain activation assessed by Functional Magnetic Resonance Imaging (fMRI) during Monetary Incentive Delay (MID) task. During MID the task, participants respond to "win" trials by pressing a button on a button box in the MRI as quickly as possible when the see a target. MID task reward outcome is defined by the contrast in fMRI signal between successful and unsuccessful reward trials during the presentation of feedback. Because this subtraction method is used to define the fMRI signal, it is possible for this value to be negative.	up to 15 weeks

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: National Institute of Mental Health (NIMH); Duke University
• Investigators: Principal Investigator: Gabriel S Dichter, PhD, UNC-Chapel Hill

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2019
• Primary Completion (Actual): July 31, 2023
• Study Completion (Actual): July 31, 2023

Study Registration Dates

• First Submitted: July 25, 2019
• First Submitted That Met QC Criteria: July 25, 2019
• First Posted (Actual): July 29, 2019

Study Record Updates

• Last Update Posted (Actual): June 21, 2024
• Last Update Submitted That Met QC Criteria: May 28, 2024
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Anhedonia
• Other Study ID Numbers: 16-2268b; R61MH110027 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Will share de-identified data through the National Database for Clinical Trials Related to Mental Illness (NDCT)

Drug and device information, study documents

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