PRISM Neurofeedback Training for MDD Anhedonic Patients

Personalizing Self Neuro-modulation Therapy for Major Depressive Disorder (MDD) With Anhedonia Using Clinical Biomarkers for MDD Subtypes

The goal of this interventional double-blind study is to demonstrate the safety and efficacy of PRISM neurofeedback training within an MDD Anhedonia sample.

The main questions it aims to answer are:

1. what clinical profile / symptoms-based biomarkers scores can be used by clinics to administer PRISM therapy in conjunction with standard care of therapy?
2. What are the initial guidelines for integrating PRISM neurofeedback training for MDD therapy with MDD Anhedonia?

Participants will be randomly assigned to one of two arms, Active, or Sham.

During the study, participants will perform the following:

• Complete clinical assessments using questionnaires, an MRI scan, and tasks that probe reward responsivity, learning, and motivation.
• Perform 15 (+/-3) neurofeedback training sessions (performed twice a week on nonconsecutive days for about 2 months).
• Complete the same clinical assessments, post-NF training MRI scan, and tasks same as in the screening/baseline stage.

Researchers will compare the sham and treatment arm to evaluate if the neurofeedback effect reduced MDD symptoms in MDD patients with Anhedonia.

Study Overview

• Status: Recruiting
• Conditions: Depression; Anhedonia
• Intervention / Treatment: Device: Active RS-EFP; Device: Sham RS-EFP

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Liora Levi, PhD; Phone Number: +972509260334; Email: liora@graymatters.health
• Study Contact Backup: Name: Adar Shani; Phone Number: +972542347770; Email: adar@graymatters.health

Study Locations

• United States
  • Massachusetts
    • Belmont, Massachusetts, United States, 02478
      • Recruiting
      • McLean Hospital
      • Sub-Investigator: Kerry J Ressler, MD
      • Sub-Investigator: Isabelle M Rosso, PhD
      • Contact: Molly Sapperstein; Phone Number: 617-855-2247; Email: neurofeedbackstudy@mclean.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Ages 22 to 65
2. Any gender and all ethnic/racial origins
3. Diagnosis of MDD with Anhedonia, established according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM5), with HDRS-21 ≥17 and SHAPS- score ≥25. MDD diagnosis will be determined via the Neuropsychiatric Interview (SCID-V for DSM-5).
4. Fall within parameters as defined in the Retrospective stage, and/or anhedonic subtype of MDD
5. Right-handed (Chapman and Chapman 1987)
6. Fluency in written and spoken English
7. Ability to give signed, informed consent either written or electronic (via REDCap eConsent)
8. Normal or corrected-to-normal vision and hearing
9. Ability to adhere to the study schedule

Exclusion Criteria:

1. A history of schizophrenia, schizoaffective disorder, schizophreniform disorder, Bipolar I disorder, or delusional disorder.
2. Lifetime diagnosis of autism or intellectual disability at discretion of investigator.
3. Diagnosis of moderate or severe substance use disorder within the last 3 months of screening visit (as defined in DSM-5-substance use disorder) or at screening visit.
4. Any prescribed Benzodiazepine which cannot be ceased for the duration of the study (with a washout period of at least 2 weeks prior to the first Prism training session) or which cannot be replaced with short-acting benzodiazepines that are taken only for sleeping during the night at equivalent daily dose of up to 3 mg.
5. Current diagnosis of posttraumatic stress disorder (PTSD).
6. Any psychotropic medication other than a stable dose of antidepressants, e.g., selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitor (SNRIs).
7. Because of the focus on RS, any past or current use of DA (Dopamine Agonist)-acting drugs (e.g., bupropion, stimulants, low doses of anti-psychotics used as an augmentation strategy). Also, exclude metformin or any other compound with DA effects.
8. Any change in - or initiation of - SSRIs or SNRIs antidepressants within the past 4 weeks. At the time of recruitment, patients must have no intention of changing their medication or psychotherapy (see also exclusion #10) during the study duration.
9. Any suicidal behavior in the past 1 year (i.e., actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behavior) prior to screening and during the screening period.
10. Recent initiation (within the past 3 months) of cognitive-behavioral therapy or any evidence-based MDD psychotherapy (Cognitive Behavior Therapy [CBT], Behavioral Activation Therapy, etc.); continuation of established maintenance supportive therapy will be permitted.
11. A history of seizures, at risk for seizure (e.g., history of significant head trauma with loss of consciousness for greater than or equal to 5 minutes or familial or personal history of epilepsy) or have been diagnosed with a seizure disorder.
12. Any unstable medical condition, as per the clinical judgment of the investigator.
13. Enrollment in another therapeutic clinical study at screening or within 2 months prior to screening, or intended enrollment within the duration of this study.
14. Women who are pregnant, nursing, or who plan to become pregnant while in the trial.
15. Contraindications to MRI (e.g., metal in body, claustrophobia).
16. Hairstyles that prevent the application of the EEG net (e.g., braids, dreadlocks, corn rows, recently dyed hair)

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: Active Arm; Subjects randomized into the Active arm will receive RS-EFP-NF Prism training as an adjunct to standard of care.	Device: Active RS-EFP; 15 (+/- 3) active NF Prism training sessions, aimed to train for upregulating the RS activity. Sessions will occur twice a week, on nonconsecutive days, over 8 consecutive weeks. Subjects will also receive two single booster sessions, one month and two months after their last training session.
Sham Comparator: Control Arm; Subjects randomized into the Control arm will receive a Sham-EFP-NF training with the same schedule as the active arm, adjunct to standard of care.	Device: Sham RS-EFP; 15 (+/- 3) sham NF Prism training sessions, aimed to train for upregulating the RS activity. Sessions will occur twice a week, on nonconsecutive days, over 8 consecutive weeks. Subjects will also receive two single sham booster sessions, one month and two months after their last training session.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HDRS-21	The HDRS (also known as the Ham-D) is the most widely used clinician-administered depression assessment scale. It is a multiple-item questionnaire used to provide an indication of depression, and as a guide to evaluate recovery. Each item on the questionnaire is scored on a 3- or 5-point scale, depending on the item, and the total score is compared to the corresponding descriptor. Assessment time is about 20 minutes.	9 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Snaith Hamilton Pleasure Scale - self reported (SHAPS-SR)	The Snaith Hamilton Pleasure Scale (Snaith et al., 1995) is a 14- item self-administered measure of anhedonic symptoms. The purpose of this assessment is to evaluate the ability to enjoy/experience pleasure in activities in the past week. Each item is rated on a 4-point Likert scale, where the total score ranges between 0 to 42 and a higher total score means a worse outcome.	9 weeks
HDRS-21	The HDRS (also known as the Ham-D) is the most widely used clinician-administered depression assessment scale. It is a multiple-item questionnaire used to provide an indication of depression, and as a guide to evaluate recovery. Each item on the questionnaire is scored on a 3- or 5-point scale, depending on the item, and the total score is compared to the corresponding descriptor. Assessment time is about 20 minutes.	3 months
Snaith Hamilton Pleasure Scale - self reported (SHAPS-SR)	The Snaith Hamilton Pleasure Scale (Snaith et al., 1995) is a 14- item self-administered measure of anhedonic symptoms. The purpose of this assessment is to evaluate the ability to enjoy/experience pleasure in activities in the past week. Each item is rated on a 4-point Likert scale, where the total score ranges between 0 to 42 and a higher total score means a worse outcome.	3 months
The clinical global impression (CGI-I)	The CGI-I Scale - of Clinical Global Impression (Guy et.al, 1976) - is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. Rated within the range of 0 to 7, lower scores indicate improved outcomes while higher scores indicate worsen outcomes.	9 weeks

Collaborators and Investigators

• Sponsor: GrayMatters Health Ltd.
• Investigators: Principal Investigator: Diego Pizzagalli, PhD, McLean Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2023
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: April 23, 2023
• First Submitted That Met QC Criteria: May 17, 2023
• First Posted (Actual): May 22, 2023

Study Record Updates

• Last Update Posted (Estimated): November 16, 2023
• Last Update Submitted That Met QC Criteria: November 15, 2023
• Last Verified: April 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: CLP011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No