Trial Outcomes & Findings for Modulating Repetitive Negative Thinking Related Brain Networks in Young Adults With Depression (NCT NCT06219681)

NCT ID: NCT06219681

Last Updated: 2026-06-17

Results Overview

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.

Recruitment status

TERMINATED

Study phase

NA

Target enrollment

54 participants

Primary outcome timeframe

Immediately post-intervention during Visit 1 (day 1)

Results posted on

2026-06-17

Participant Flow

Participants were recruited from the Tulsa metropolitan area through the Laureate Institute for Brain Research (LIBR). Recruitment methods included outreach by the LIBR clinical team, as well as newspaper, flyers, radio, and Facebook advertisements. The study targeted young adults (ages 18-35) with Major Depressive Disorder. Recruitment began in January 2024 and was terminated prematurely due to the Principal Investigator's departure.

A total of 54 participants signed the informed consent form, but only 42 were randomized and assigned to study arms. The remaining 12 participants were excluded prior to group assignment due to screening failures (e.g., exclusionary psychiatric diagnoses, positive drug tests, pregnancy), loss to follow-up, or voluntary withdrawal before the first visit.

Participant milestones

Participant milestones
Measure
Active Neurofeedback
Receiving feedback signals from the repetitive negative thinking (RNT)-related brain functional connectivity
Sham Neurofeedback
Receiving artificially generated feedback signals.
Overall Study
STARTED
22
20
Overall Study
COMPLETED
19
18
Overall Study
NOT COMPLETED
3
2

Reasons for withdrawal

Reasons for withdrawal
Measure
Active Neurofeedback
Receiving feedback signals from the repetitive negative thinking (RNT)-related brain functional connectivity
Sham Neurofeedback
Receiving artificially generated feedback signals.
Overall Study
Withdrawal by Subject
3
1
Overall Study
Protocol Violation
0
1

Baseline Characteristics

Of 42 randomized participants, 27 had usable fMRI data at Visit 1 (Active n=15, Sham n=12). Remaining 15 were excluded due to fMRI data quality issues such as excessive head motion.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Active Neurofeedback
n=22 Participants
Receiving feedback signals from the repetitive negative thinking (RNT)-related brain functional connectivity
Sham Neurofeedback
n=20 Participants
Receiving artificially generated feedback signals.
Total
n=42 Participants
Total of all reporting groups
Age, Continuous
27.3 years old
STANDARD_DEVIATION 4.9 • n=22 Participants
27.1 years old
STANDARD_DEVIATION 5.8 • n=20 Participants
27.2 years old
STANDARD_DEVIATION 5.3 • n=42 Participants
Sex: Female, Male
Female
17 Participants
n=22 Participants
16 Participants
n=20 Participants
33 Participants
n=42 Participants
Sex: Female, Male
Male
5 Participants
n=22 Participants
4 Participants
n=20 Participants
9 Participants
n=42 Participants
Race (NIH/OMB)
American Indian or Alaska Native
1 Participants
n=22 Participants
0 Participants
n=20 Participants
1 Participants
n=42 Participants
Race (NIH/OMB)
Asian
1 Participants
n=22 Participants
2 Participants
n=20 Participants
3 Participants
n=42 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=22 Participants
0 Participants
n=20 Participants
0 Participants
n=42 Participants
Race (NIH/OMB)
Black or African American
2 Participants
n=22 Participants
3 Participants
n=20 Participants
5 Participants
n=42 Participants
Race (NIH/OMB)
White
14 Participants
n=22 Participants
10 Participants
n=20 Participants
24 Participants
n=42 Participants
Race (NIH/OMB)
More than one race
3 Participants
n=22 Participants
5 Participants
n=20 Participants
8 Participants
n=42 Participants
Race (NIH/OMB)
Unknown or Not Reported
1 Participants
n=22 Participants
0 Participants
n=20 Participants
1 Participants
n=42 Participants
Functional Connectivity between rAI and rSTS at baseline
0.3170 beta-values
STANDARD_DEVIATION 0.5142 • n=15 Participants • Of 42 randomized participants, 27 had usable fMRI data at Visit 1 (Active n=15, Sham n=12). Remaining 15 were excluded due to fMRI data quality issues such as excessive head motion.
0.1474 beta-values
STANDARD_DEVIATION 0.2001 • n=12 Participants • Of 42 randomized participants, 27 had usable fMRI data at Visit 1 (Active n=15, Sham n=12). Remaining 15 were excluded due to fMRI data quality issues such as excessive head motion.
0.2416 beta-values
STANDARD_DEVIATION 0.4083 • n=27 Participants • Of 42 randomized participants, 27 had usable fMRI data at Visit 1 (Active n=15, Sham n=12). Remaining 15 were excluded due to fMRI data quality issues such as excessive head motion.
Brief State Rumination Inventory (BSRI) Total Score at Baseline
383.36 score
STANDARD_DEVIATION 179.97 • n=22 Participants
455.05 score
STANDARD_DEVIATION 201.94 • n=20 Participants
417.50 score
STANDARD_DEVIATION 191.84 • n=42 Participants
Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Baseline
19.18 score
STANDARD_DEVIATION 7.27 • n=22 Participants • One participant (Sham) was missing MADRS data at Visit 1, resulting in n=41 (Active n=22, Sham n=19).
16.84 score
STANDARD_DEVIATION 7.73 • n=19 Participants • One participant (Sham) was missing MADRS data at Visit 1, resulting in n=41 (Active n=22, Sham n=19).
18.10 score
STANDARD_DEVIATION 7.48 • n=41 Participants • One participant (Sham) was missing MADRS data at Visit 1, resulting in n=41 (Active n=22, Sham n=19).

PRIMARY outcome

Timeframe: Immediately post-intervention during Visit 1 (day 1)

Population: Of the 42 randomized participants (Active n=22, Sham n=20), 27 had complete fMRI data for Visit 1 and were included in the analysis (Active n=15, Sham n=12). Participants were excluded due to missing Visit 1 fMRI data or data quality issues such as excessive head motion.

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.

Outcome measures

Outcome measures
Measure
Sham Neurofeedback
n=12 Participants
Receiving artificially generated feedback signals.
Active Neurofeedback
n=15 Participants
Receiving feedback signals from the repetitive negative thinking (RNT)-related brain functional connectivity
Functional Connectivity Change Between Right Anterior Insular (rAI) and Right Superior Temporal Sulcus (rSTS) Within Visit1
0.5553 beta-value
Standard Deviation 0.1594
-0.1140 beta-value
Standard Deviation 0.0731

SECONDARY outcome

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

Population: All 42 randomized participants who completed Visit 1 were included in the analysis (Active n=22, Sham n=20).

The BSRI is a self-report scale to measure state rumination. A higher score indicates higher state rumination with a maximum score of 800 and the minimum score of 0. Change scores were calculated as post-intervention score minus pre-intervention score at Visit 1. A negative change score indicates reduction in state rumination.

Outcome measures

Outcome measures
Measure
Sham Neurofeedback
n=20 Participants
Receiving artificially generated feedback signals.
Active Neurofeedback
n=22 Participants
Receiving feedback signals from the repetitive negative thinking (RNT)-related brain functional connectivity
Changes in Brief State Rumination Inventory (BSRI) Total Score From Pre- to Post-Intervention at Visit 1
-3.20 score
Standard Deviation 265.07
70.82 score
Standard Deviation 175.72

SECONDARY outcome

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

Population: Of the 42 randomized participants (Active n=22, Sham n=20), 36 had MADRS data at both visits and were included in the analysis (Active n=18, Sham n=18). Six participants were excluded due to missing Visit 1 (n=1) or Visit 2 assessments (n=5).

The MADRS is an interviewer-rated scale to measure the severity of depressive symptoms. A higher score indicates severer depression with a maximum score of 60 and a minimum score of 0. Change scores were calculated as Visit 2 score minus Visit 1 score. A negative change score indicates improvement in depressive symptoms.

Outcome measures

Outcome measures
Measure
Sham Neurofeedback
n=18 Participants
Receiving artificially generated feedback signals.
Active Neurofeedback
n=18 Participants
Receiving feedback signals from the repetitive negative thinking (RNT)-related brain functional connectivity
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline to Follow-up
-2.44 score
Standard Deviation 6.64
-1.44 score
Standard Deviation 5.22

OTHER_PRE_SPECIFIED outcome

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

Population: Of the 42 randomized participants (Active n=22, Sham n=20), 19 had complete fMRI data for both visits (Active n=8, Sham n=11). Participants were excluded due to missing Visit 2 (n=10), fMRI data quality issues such as excessive head motion, or incomplete task run acquisition.

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 Visit 2 beta-value minus Visit 1 beta-value.

Outcome measures

Outcome measures
Measure
Sham Neurofeedback
n=11 Participants
Receiving artificially generated feedback signals.
Active Neurofeedback
n=8 Participants
Receiving feedback signals from the repetitive negative thinking (RNT)-related brain functional connectivity
Functional Connectivity Change Between Right Anterior Insular (rAI) and Right Superior Temporal Sulcus (rSTS) From Visit1 to Follow-up (Visit 2)
-0.0037 beta-value
Standard Deviation 0.2300
0.0044 beta-value
Standard Deviation 0.1754

Adverse Events

Active Neurofeedback

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Sham Neurofeedback

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Aki Tsuchiyagaito

Laureate Institute for Brain Research

Phone: (918) 502-5100

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place