Amygdala Neurofeedback for Depression - Large Scale Clinical Trial

NCT ID: NCT05703256

Last Updated: 2025-04-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-06-01
• Study Completion Date: 2028-04-30

Brief Summary

The goal of this study is to evaluate whether rtfMRI-nf training to increase the amygdala response to positive memories may serve as a stand-alone intervention for major depressive disorder

Detailed Description

Previous research has shown that real-time fMRI neurofeedback (rtfMRI-nf) training aimed at increasing the amygdala's response to positive autobiographical memory recall holds therapeutic potential for treating patients with major depressive disorder (MDD), as clinically significant decreases in clinician administered and self-report measures of depression severity were observed following two rtfMRI amygdala neurofeedback sessions. Furthermore, rtfMRI amygdala neurofeedback changed emotional processing towards a positive bias. The goal of the current study is to confirm the clinical efficacy of this intervention in a new sample of depressed participants. Thus, over the course of four years, we will conduct a randomized double-blind clinical trial examining the clinical and cognitive effects of amygdala rtfMRI-nf compared to yoked sham rtfMRI-nf (seeing the amygdala activity of another participant during training) in 200 participants with MDD from the Pittsburgh metropolitan area. Participants will undergo two rtfMRI-nf sessions. Half of the participants will receive amygdala neurofeedback and half will receive yoked sham neurofeedback. Participants will complete the BDI-II monthly for one year following completion of the neurofeedback intervention. The rationale for the proposed research is to provide new insights into possible mechanistic solutions for MDD, and to further guide development of this rtfMRI-nf intervention into a treatment for MDD.

Conditions

Major Depressive Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Amygdala real-time fMRI neurofeedback

Amygdala neurofeedback - attempt to upregulate the left amygdala during positive autobiographical memory recall via real time fMRI neurofeedback from the amygdala. Two sessions will be performed one week apart.

Group Type: EXPERIMENTAL

Amygdala real-time fMRI neurofeedback

Intervention Type: DEVICE

Participants are shown activity from their left amygdala in real time and are instructed to increase the level of activity in that region by thinking of positive autobiographical memories

Sham feedback

Yoked sham - participants will see the amygdala activity of another subject who completed the intervention. Two sessions will be performed one week apart.

Group Type: SHAM_COMPARATOR

Sham feedback

Intervention Type: DEVICE

Participants are shown activity from another participant's left amygdala who previously completed the task and are instructed to increase the level of activity in that region by thinking of positive autobiographical memories

Interventions

Amygdala real-time fMRI neurofeedback

Participants are shown activity from their left amygdala in real time and are instructed to increase the level of activity in that region by thinking of positive autobiographical memories

Intervention Type: DEVICE

Sham feedback

Participants are shown activity from another participant's left amygdala who previously completed the task and are instructed to increase the level of activity in that region by thinking of positive autobiographical memories

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• ages 18 - 55
• primary diagnosis of MDD and are currently depressed
• able to give written informed consent prior to participation
• unmedicated OR are stable on an antidepressant regime (at least 4 weeks to ensure symptoms are stable). Effective medications will not be discontinued for the purposes of the study.

Exclusion Criteria

• clinically significant or unstable cardiovascular, pulmonary, endocrine, neurological, gastrointestinal illness or unstable medical disorder
• Current severe DSM-V alcohol or substance use disorder, with the exception of nicotine or caffeine. Clinician will access subjects' alcohol and substance use on a case-by-case to determine whether specific cases of mild or moderate alcohol or substance use would also interfere with the effects of the intervention.
• history of traumatic brain injury
• unable to complete MRI scan due to claustrophobia or general MRI exclusions (e.g., shrapnel inside body)
• currently pregnant or breast feeding
• unable to complete questionnaires written in English
• current (within 3 weeks of testing) use of any antipsychotics, anticonvulsants, stimulants, benzodiazepines, beta-blockers, or other medications (except antidepressants) likely to influence cerebral blood flow. Effective medications will not be discontinued for the purposes of the study.
• diagnosis of psychotic or organic mental disorder, bipolar I or II disorder.
• eye problems or difficulties in corrected vision.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Kymberly Young

OTHER

Sponsor Role: lead

Responsible Party

Kymberly Young

Associate Professor of Psychiatry

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Kymberly Young, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Kymberly Young, PhD

Role: CONTACT

youngk@pitt.edu

412-648-6179

Lisa Stupar

Role: CONTACT

stuparlm@upmc.edu

412-383-8100

Facility Contacts

Kymberly Young, PhD

Role: primary

youngk@pitt.edu

References

Young KD, Zotev V, Phillips R, Misaki M, Yuan H, Drevets WC, Bodurka J. Real-time FMRI neurofeedback training of amygdala activity in patients with major depressive disorder. PLoS One. 2014 Feb 11;9(2):e88785. doi: 10.1371/journal.pone.0088785. eCollection 2014.

Reference Type: BACKGROUND

PMID: 24523939 (View on PubMed)

Young KD, Siegle GJ, Zotev V, Phillips R, Misaki M, Yuan H, Drevets WC, Bodurka J. Randomized Clinical Trial of Real-Time fMRI Amygdala Neurofeedback for Major Depressive Disorder: Effects on Symptoms and Autobiographical Memory Recall. Am J Psychiatry. 2017 Aug 1;174(8):748-755. doi: 10.1176/appi.ajp.2017.16060637. Epub 2017 Apr 14.

Reference Type: BACKGROUND

PMID: 28407727 (View on PubMed)

Young KD, Misaki M, Harmer CJ, Victor T, Zotev V, Phillips R, Siegle GJ, Drevets WC, Bodurka J. Real-Time Functional Magnetic Resonance Imaging Amygdala Neurofeedback Changes Positive Information Processing in Major Depressive Disorder. Biol Psychiatry. 2017 Oct 15;82(8):578-586. doi: 10.1016/j.biopsych.2017.03.013. Epub 2017 Mar 28.

Reference Type: BACKGROUND

PMID: 28476207 (View on PubMed)

Other Identifiers

R01MH130337

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY23010004

Identifier Type: -

Identifier Source: org_study_id