Development of a Novel Transdiagnostic Intervention for Anhedonia - R61 Phase

• Sponsor: University of North Carolina, Chapel Hill (Other)
• Overall Status: Completed
• CT.gov ID: NCT02874534
• Collaborator: Duke University (Other), National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 57
• Location: 1
• Arms: 2
• Actual Duration (Months): 25.3
• Patients Per Site Per Month: 2.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Anhedonia	Behavioral: Behavioral Activation; Behavioral: Mindfulness Treatment	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 57 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Development of a Novel Transdiagnostic Intervention for Anhedonia - R61 Phase
• Actual Study Start Date: Jun 22, 2017
• Actual Primary Completion Date: Jul 31, 2019
• Actual Study Completion Date: Jul 31, 2019

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to Week 15 in Neural Activation [Baseline, 15 weeks]

   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.

Secondary Outcome Measures

1. Change From Baseline to Week 15 in Snaith-Hamilton Pleasure Scale Score [Baseline, 15 weeks]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UNC Chapel Hill	Chapel Hill	North Carolina	United States	27599

Sponsors and Collaborators

• University of North Carolina, Chapel Hill
• Duke University
• National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Gabriel S Dichter, PhD, UNC-Chapel Hill

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 23, 2019

More Information

Publications

None provided.

• Responsible Party: University of North Carolina, Chapel Hill
• ClinicalTrials.gov Identifier: NCT02874534
• Other Study ID Numbers: 16-2268a; R61MH110027-01A1
• First Posted: Aug 22, 2016
• Last Update Posted: Apr 24, 2020
• Last Verified: Feb 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Anhedonia

Study Results

Participant Flow

Arm/Group Title	Behavioral Activation	Mindfulness Treatment
Arm/Group Description	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 Activation: Treatment will consist of 15 weekly 45-minute sessions.	Behavioral Activation Treatment for Anhedonia (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. Mindfulness Treatment: Treatment will consist of 15 weekly 45-minute sessions.
Period Title: Overall Study
STARTED	31	26
COMPLETED	23	15
NOT COMPLETED	8	11

Baseline Characteristics

Arm/Group Title	Behavioral Activation	Mindfulness Treatment	Total
Arm/Group Description	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 Activation: Treatment will consist of 15 weekly 45-minute sessions.	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. Mindfulness Treatment: Treatment will consist of 15 weekly 45-minute sessions.	Total of all reporting groups
Overall Participants	31	26	57
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	27.61 (8.47)	33.35 (9.25)	30.23 (9.22)
Sex: Female, Male (Count of Participants)
Female	23 74.2%	19 73.1%	42 73.7%
Male	8 25.8%	7 26.9%	15 26.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	7 22.6%	3 11.5%	10 17.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	4 12.9%	5 19.2%	9 15.8%
White	18 58.1%	16 61.5%	34 59.6%
More than one race	2 6.5%	1 3.8%	3 5.3%
Unknown or Not Reported	0 0%	1 3.8%	1 1.8%
Region of Enrollment (Count of Participants)
United States	31 100%	26 100%	57 100%
SHAPS (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	37.61 (4.38)	38.00 (5.25)	37.79 (4.76)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Week 15 in Neural Activation
Description	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.
Time Frame	Baseline, 15 weeks

Outcome Measure Data

Analysis Population Description

The fMRI data quality for one participant was inadequate and was excluded from the analysis.

Arm/Group Title	Behavioral Activation	Mindfulness Treatment
Arm/Group Description	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 Activation: Treatment will consist of 15 weekly 45-minute sessions.	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. Mindfulness Treatment: Treatment will consist of 15 weekly 45-minute sessions.
Measure Participants	22	15
Mean (Standard Deviation) [Z-score]	0.0075 (0.23)	-0.1059 (0.21)

2. Secondary Outcome

Title	Change From Baseline to Week 15 in Snaith-Hamilton Pleasure Scale Score
Description	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.
Time Frame	Baseline, 15 weeks

Outcome Measure Data

Analysis Population Description

The fMRI data quality for one participant was inadequate and was excluded from the analysis.

Arm/Group Title	Behavioral Activation	Mindfulness Treatment
Arm/Group Description	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 Activation: Treatment will consist of 15 weekly 45-minute sessions.	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. Mindfulness Treatment: Treatment will consist of 15 weekly 45-minute sessions.
Measure Participants	22	15
Mean (Standard Deviation) [units on a scale]	8.0 (4.87)	9.3 (7.6)

Adverse Events

Time Frame	From initial assessment through post treatment scan, a total of approximately 3 to 5 months.
Adverse Event Reporting Description	Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.
Arm/Group Title	Behavioral Activation		Mindfulness Treatment
Arm/Group Description	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 Activation: Treatment will consist of 15 weekly 45-minute sessions.		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. Mindfulness Treatment: Treatment will consist of 15 weekly 45-minute sessions.
All Cause Mortality
	Behavioral Activation		Mindfulness Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0%)		0/26 (0%)
Serious Adverse Events
	Behavioral Activation		Mindfulness Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0%)		0/26 (0%)
Other (Not Including Serious) Adverse Events
	Behavioral Activation		Mindfulness Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/31 (32.3%)		12/26 (46.2%)
Cardiac disorders
Hypertension	1/31 (3.2%)	1	1/26 (3.8%)	1
Presyncopal Episode	0/31 (0%)	0	1/26 (3.8%)	1
Endocrine disorders
Elevated TSH	0/31 (0%)	0	1/26 (3.8%)	1
Eye disorders
Intermittent eye twitching	1/31 (3.2%)	1	0/26 (0%)	0
Infections and infestations
Cold Symptoms	2/31 (6.5%)	2	1/26 (3.8%)	1
Flu	0/31 (0%)	0	1/26 (3.8%)	1
Pneumonia	0/31 (0%)	0	1/26 (3.8%)	1
Sinus Infection	2/31 (6.5%)	2	1/26 (3.8%)	1
Upper respiratory infection	1/31 (3.2%)	1	0/26 (0%)	0
Streptococcal pharyngitis	0/31 (0%)	0	1/26 (3.8%)	1
Metabolism and nutrition disorders
Decreased appetite	1/31 (3.2%)	1	0/26 (0%)	0
Musculoskeletal and connective tissue disorders
Back Pain	2/31 (6.5%)	3	1/26 (3.8%)	1
Hip Pain	1/31 (3.2%)	1	0/26 (0%)	0
Broken Collar Bone	0/31 (0%)	0	1/26 (3.8%)	1
Worsening arthritis	0/31 (0%)	0	1/26 (3.8%)	1
Psychiatric disorders
Suicidal Ideation	1/31 (3.2%)	1	0/26 (0%)	0
Skin and subcutaneous tissue disorders
Burns on right forearm	1/31 (3.2%)	1	0/26 (0%)	0
Scalp Acne	0/31 (0%)	0	1/26 (3.8%)	1
Telogen Effluvium	0/31 (0%)	0	1/26 (3.8%)	1

Limitations/Caveats

These results represent the complete therapeutic target results for this trial's R61 phase that may be combined with the results of the ongoing clinical endpoint R33 phase study whose final results will be reported in NCT04036136.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.