Modulating Repetitive Negative Thinking Related Brain Networks in Young Adults With Depression

NCT06219681 | Terminated Results

• 2 other identifiers: 2023-002P20GM121312
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

In this project, the investigators use real-time fMRI neurofeedback (rtfMRI-nf) to causally relate dysfunction of right anterior insula (rAI) and right superior temporal sulcus (rSTS) connectivity with the intensity of repetitive negative thinking (RNT). The investigators hypothesize that rtfMRI-nf reducing rAI-rSTS connectivity would reduce RNT. The investigators propose a randomized double-blind, sham-controlled trial of rtfMRI-nf with 110 young adults (n=55/arm) with major depressive disorder (MDD) and high trait-RNT levels.

Conditions

Depressive Disorder, Major

Outcome Measures

Primary Outcomes (1)

• Functional Connectivity Change Between Right Anterior Insular (rAI) and Right Superior Temporal Sulcus (rSTS) Within Visit1

  Functional connectivity between rAI and rSTS was assessed using psychophysiological interaction (PPI) analysis of fMRI BOLD signal. Beta-values derived from PPI analysis represent the strength of connectivity; higher positive values indicate stronger functional coupling between regions. Change scores were calculated as post-intervention beta-value minus pre-intervention beta-value within Visit 1. A negative value indicates reduced connectivity following neurofeedback.

  Immediately post-intervention during Visit 1 (day 1)

Secondary Outcomes (2)

• Changes in Brief State Rumination Inventory (BSRI) Total Score From Pre- to Post-Intervention at Visit 1

  From baseline (pre-scan at Visit 1, Day 1) to immediately after neurofeedback intervention (post-scan at Visit 1, Day 1)

• Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline to Follow-up

  From baseline at Visit 1 (Day 1) to follow-up at Visit 2 (1 week after Visit 1)

Other Outcomes (1)

• Functional Connectivity Change Between Right Anterior Insular (rAI) and Right Superior Temporal Sulcus (rSTS) From Visit1 to Follow-up (Visit 2)

  From baseline scan at Visit 1 (Day 1) to follow-up scan at Visit 2 (1 week after Visit 1)

Study Arms (2)

Active neurofeedback

EXPERIMENTAL

Receiving feedback signals from the repetitive negative thinking (RNT)-related brain functional connectivity

Behavioral: Active neurofeedback

Sham neurofeedback

SHAM COMPARATOR

Receiving artificially generated feedback signals.

Behavioral: Sham neurofeedback

Interventions

Active neurofeedback BEHAVIORAL

The session will be done on an individual basis. The active group will receive neurofeedback training from the repetitive negative thinking (RNT) related brain functional connectivity.

Active neurofeedback

Sham neurofeedback BEHAVIORAL

The session will be done on an individual basis. The sham group will receive neurofeedback training from an artificially generated random feedback signal.

Sham neurofeedback

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Young adults ages 18-35
• Participants who are able to give written informed consent prior to participation
• Meeting DSM-5 diagnostic criteria for MDD who are currently depressed defined by the MINI
• Participants who have RNT symptoms (Brooding subscale of Ruminative Response Scale: RRS-B ≥ 13)

You may not qualify if:

• Moderate to severe traumatic brain injury (\>30 min. loss of consciousness or \>24 hours posttraumatic amnesia) or other neurocognitive disorder with evidence of neurological deficits
• Presence of co-morbid medical conditions not limited to but including cardiovascular (e.g., history of acute coronary event, stroke), pulmonary, endocrine, neurological diseases (e.g., Parkinson's disease), or gastrointestinal illness, as well as pain disorders
• Current significant suicidal ideation or suicide attempt within the previous 12 months
• Current psychosis
• Schizophrenia or schizoaffective disorder
• Substance use disorder within the previous 12 months, except for mild alcohol, cannabis, or tobacco use disorder defined as less than 4 symptoms of the criteria for substance use disorder according to the MINI
• Current diagnosis of post-traumatic disorder (PTSD) defined by the MINI
• Severe claustrophobia
• Bodily implants of unsafe paramagnetic materials such as pacemakers and aneurysm clips
• Pregnancy
• Current regular use of cardiovascular medications with a direct vasomotor effect, namely beta- or alpha-beta-blockers, clonidine, and antianginal agents.
• Current use of more than three psychotropic medications
• Evidence of recreational drug use from a urine test
• Commencement of psychotropic medication for depression and/or anxiety less than a month before the study enrollment
• Commencement of psychological therapy less than a month before the study enrollment

Sponsors & Collaborators

• Laureate Institute for Brain Research, Inc.: lead
• National Institute of General Medical Sciences (NIGMS): collaborator

Study Sites (1)

Laureate Institute for Brain Research

Tulsa, Oklahoma, 74136, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Limitations and Caveats

The study was terminated prematurely due to the Principal Investigator's departure, resulting in a smaller sample size than planned. Outcome measure data are based on available fMRI data after quality control exclusions and should be interpreted as preliminary.

Results Point of Contact

• Title: Aki Tsuchiyagaito
• Organization: Laureate Institute for Brain Research

ATsuchiyagaito@laureateinstitute.org

(918) 502-5100

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2024
• First Posted: January 23, 2024
• Study Start: January 12, 2024
• Primary Completion: April 4, 2025
• Study Completion: April 4, 2025
• Last Updated: June 17, 2026
• Results First Posted: June 17, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)