Development of a Novel Transdiagnostic Intervention for Anhedonia - R61 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 propose 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 will examine 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. In this phase of the project, the investigators will also use fMRI to determine the optimal dose of the intervention (Aim 2).

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Chapel Hill

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. 18-50 years old and treatment seeking;
2. SHAPS scores ≥ 20, corresponding to clinically significant anhedonia;
3. Clinician's Global Impression Scale-Severity score (CGI-S) > 3 to assure a clinically impaired sample;
4. 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:

1. Those for whom medication management is the primary gold-standard treatment, including those with bipolar disorder/mania, schizophrenia spectrum, and other psychotic disorders;
2. 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);
3. Those who may have difficulty understanding the cognitive components of BATA, including those with intellectual disability, neurocognitive disorders, and dissociative disorders;
4. Feeding and eating disorders which may have confounding effects on the fMRI signal;
5. Substance Use Disorders given confounding effects of substances of abuse on the fMRI signal;
6. Suicidal intent and plan;
7. 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;
8. Currently pregnant, as measured by urine pregnancy screen immediately before MRI scans;
9. Positive urinalysis screen for cocaine, marijuana, opiates, methadone, amphetamines, and benzodiazepines (conducted on-site via Biosite Triage Meter Plus) at study entry.
10. No neurological conditions (e.g., history of stroke, seizure, or TBI);
11. 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: Single

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 From Baseline to Week 15 in Neural Activation	Change due to BATA, relative to MBCT, from baseline in right caudate nucleus activation during the anticipation phase of the Monetary Incentive Delay (MID) task assessed by Functional Magnetic Resonance Imaging (fMRI). The BOLD (Blood Oxygen Level-Dependent signal change is expressed as a z-score that represents the magnitude of change relative to baseline. A score of 0 would correspond to no change, and a score of 1 would represent 1 standard deviation of change. The difference in z-scores between the BATA and the MBCT groups reflects the difference in change in fMRI responses between the two treated groups. Thus even a score of 0 in the BATA group may reflect greater change than observed in the MBCT group if change in the MBCT group is negative.	Baseline, 15 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 15 in Snaith-Hamilton Pleasure Scale Score	The Snaith-Hamilton Pleasure Scale (SHAPS), used to assess hedonic capacity. The sum of the 14 items scores ranges from 0 to 56. A higher score represents more anhedonic symptoms. The below means represent change in units on the Snaith-Hamilton Pleasure Scale.	Baseline, 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): June 22, 2017
• Primary Completion (Actual): July 31, 2019
• Study Completion (Actual): July 31, 2019

Study Registration Dates

• First Submitted: August 17, 2016
• First Submitted That Met QC Criteria: August 17, 2016
• First Posted (Estimate): August 22, 2016

Study Record Updates

• Last Update Posted (Actual): April 24, 2020
• Last Update Submitted That Met QC Criteria: April 23, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Anhedonia
• Other Study ID Numbers: 16-2268a; R61MH110027-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Data will be shared via the NIMH Data Archive (NDA), collection #2595. Investigators may access the deidentified IPD directly from NDA without needing to contact the study team directly.
• IPD Sharing Time Frame: Time Frame: Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication.
• IPD Sharing Access Criteria: To request access to data, you must be sponsored by an NIH-recognized institution with a Federalwide Assurance and have a research related need to access NDA data. See https://nda.nih.gov/get/access-data.html for more information.

Drug and device information, study documents

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