Depressive Disorder, MajorCNF-RNTNCT06219681
Modulating Repetitive Negative Thinking Related Brain Networks in Young Adults With Depression
A study testing Active neurofeedback in people with Depressive Disorder, Major, run by Laureate Institute for Brain Research, Inc. at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 35 years
- Conditions the study is for
- Depressive Disorder, Major
- What is being tested?
- Active neurofeedback
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 54 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Jan 2024to 4 Apr 2025
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 18Show fewer
- 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
- Participants who have a clinically significant or unstable cardiovascular, pulmonary, endocrine, neurological, gastrointestinal illness or unstable medical disorder will be excluded
- Participants who, on arrival to the study, have a temperature greater than 100.4°F will not be allowed to initiate the study
- The majority of the assessments proposed for this study have not been translated from English, thus, non-English speaking volunteers will be excluded
Trial locations and contacts
1 site in 1 country.
United States1 site
Laureate Institute for Brain Research
Tulsa, Oklahoma, 74136
About this study
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.
Read the detailed description
Young adult mental health is crucial, as 1 in 10 young adults (ages 18-25) suffer from major depressive disorder (MDD), impacting long-term outcomes such as comorbid mental disorders, unemployment and suicide . With increasing rates of MDD among young adults, new explanatory disease models focusing on targetable disease-modifying processes (DMPs) are needed. Repetitive negative thinking (RNT) is a key DMP in MDD, involving difficulty controlling distressing thoughts and past events , and predicting depression severity and suicidal ideation/attempts in early adulthood. Current treatments, such as medication and psychotherapy including cognitive-behavioral therapy (CBT), often have limited effectiveness for MDD, with higher levels of RNT associated with slower and poorer response rates. In theory, novel treatments designed to modify the neurobiological mechanisms underlying RNT could facilitate recovery in MDD. Real-time functional Magnetic Resonance Imaging neurofeedback (rtfMRI-nf) is a non-invasive method, providing individuals with feedback concerning their brain activity in order to facilitate one's self-control.
Our preliminary studies identified a circuit with stronger connectivity between the right anterior insular (rAI, emotional salience processing hub) and the right superior temporal sulcus (rSTS, episodic memory/language processing area), correlating with the severity of RNT apart from depression. This finding aligns with the framework that views RNT as heightened evaluative and dialogic inner speech, resulting from an inability to disengage from self-critical and threatening interpretations of episodic memories. The investigators propose that excessive functional connectivity between the rAI and STS may contribute to RNT in young adults with MDD.
This project is a research project at the Laureate Institute for Brain Research (LIBR). In this project, the investigators use rtfMRI-nf to causally relate dysfunction of rAI-rSTS connectivity with the intensity of 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 MDD and high trait-RNT levels. Primary outcome will be active vs. sham rtfMRI-nf's effect on rAI-rSTS connectivity. Secondary outcomes will be active vs. sham rtfMRI-nf's effect on state-RNT (Brief State Rumination Inventory, BSRI) and depression severity (Montgomery-Asberg Depression Rating Scale, MADRS). Exploratory outcomes will be the relationship between reducing rAI-rSTS connectivity and BSRI scores. Participants will perform a self-regulation task involving neurofeedback, receiving either real-time feedback on rAI-rSTS connectivity (active group) or artificial feedback unrelated to rAI-rSTS connectivity (sham group). The investigators will collect data across two visits, one week apart. The first visit will include five runs of the self-regulation task, the middle three containing the neurofeedback condition (Visit 1). The second visit will include one run of the self-regulation task without the neurofeedback condition 1-week later (Visit 2).
- Conditions
- Depressive Disorder, Major
- Being tested
- Active neurofeedback, Sham neurofeedback
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active neurofeedbackBehavioural
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.
Sham neurofeedbackBehavioural
The session will be done on an individual basis. The sham group will receive neurofeedback training from an artificially generated random feedback signal.
| Study group | Role | What they receive |
|---|---|---|
| Active neurofeedback | Experimental | Receiving feedback signals from the repetitive negative thinking (RNT)-related brain functional connectivity Receives: Behavioral: Active neurofeedback |
| Sham neurofeedback | Sham comparator | Receiving artificially generated feedback signals. Receives: Behavioral: Sham neurofeedback |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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
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.
Measured: From baseline at Visit 1 (Day 1) to follow-up at Visit 2 (1 week after Visit 1)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2024
- Study start12 Jan 2024
- Primary completion4 Apr 2025
- Study completion4 Apr 2025
Why it stopped: Terminated due to PI resignation. Not related to safety, efficacy, or administrative mandate.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Depressive Disorder, MajorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Laureate Institute for Brain Research, Inc.
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of General Medical Sciences (NIGMS)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06219681
- Sponsor's protocol ID
- 2023-002
- Other IDs
- P20GM121312
- Acronym
- CNF-RNT
- Status last verified
- May 2026
- First submitted
- 12 Jan 2024
- Last updated
- 17 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modulating Repetitive Negative Thinking Related Brain Networks in Young Adults With Depression
- ClinicalTrials.gov ID
- NCT06219681
- Acronym / sponsor ID
- CNF-RNT / 2023-002
- Conditions
- Depressive Disorder, Major
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated due to PI resignation. Not related to safety, efficacy, or administrative mandate.
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Laureate Institute for Brain Research, Inc.University, hospital or other
- Collaborators
- National Institute of General Medical Sciences (NIGMS)
- Study start
- 12 Jan 2024 (actual)
- Primary completion
- 4 Apr 2025 (actual)
- Study completion
- 4 Apr 2025 (actual)
- First posted
- 23 Jan 2024 (actual)
- Results
- Posted 17 Jun 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Young adult mental health is crucial, as 1 in 10 young adults (ages 18-25) suffer from major depressive disorder (MDD), impacting long-term outcomes such as comorbid mental disorders, unemployment and suicide . With increasing rates of MDD among young adults, new explanatory disease models focusing on targetable disease-modifying processes (DMPs) are needed. Repetitive negative thinking (RNT) is a key DMP in MDD, involving difficulty controlling distressing thoughts and past events , and predicting depression severity and suicidal ideation/attempts in early adulthood. Current treatments, such as medication and psychotherapy including cognitive-behavioral therapy (CBT), often have limited effectiveness for MDD, with higher levels of RNT associated with slower and poorer response rates. In theory, novel treatments designed to modify the neurobiological mechanisms underlying RNT could facilitate recovery in MDD. Real-time functional Magnetic Resonance Imaging neurofeedback (rtfMRI-nf) is a non-invasive method, providing individuals with feedback concerning their brain activity in order to facilitate one's self-control.
Our preliminary studies identified a circuit with stronger connectivity between the right anterior insular (rAI, emotional salience processing hub) and the right superior temporal sulcus (rSTS, episodic memory/language processing area), correlating with the severity of RNT apart from depression. This finding aligns with the framework that views RNT as heightened evaluative and dialogic inner speech, resulting from an inability to disengage from self-critical and threatening interpretations of episodic memories. The investigators propose that excessive functional connectivity between the rAI and STS may contribute to RNT in young adults with MDD.
This project is a research project at the Laureate Institute for Brain Research (LIBR). In this project, the investigators use rtfMRI-nf to causally relate dysfunction of rAI-rSTS connectivity with the intensity of 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 MDD and high trait-RNT levels. Primary outcome will be active vs. sham rtfMRI-nf's effect on rAI-rSTS connectivity. Secondary outcomes will be active vs. sham rtfMRI-nf's effect on state-RNT (Brief State Rumination Inventory, BSRI) and depression severity (Montgomery-Asberg Depression Rating Scale, MADRS). Exploratory outcomes will be the relationship between reducing rAI-rSTS connectivity and BSRI scores. Participants will perform a self-regulation task involving neurofeedback, receiving either real-time feedback on rAI-rSTS connectivity (active group) or artificial feedback unrelated to rAI-rSTS connectivity (sham group). The investigators will collect data across two visits, one week apart. The first visit will include five runs of the self-regulation task, the middle three containing the neurofeedback condition (Visit 1). The second visit will include one run of the self-regulation task without the neurofeedback condition 1-week later (Visit 2).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active neurofeedback | Experimental | Behavioral: Active neurofeedbackReceiving feedback signals from the repetitive negative thinking (RNT)-related brain functional connectivity |
| Sham neurofeedback | Sham comparator | Behavioral: Sham neurofeedbackReceiving artificially generated feedback signals. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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)
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Active neurofeedbackThe 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. | Behavioural | Active neurofeedback |
| Sham neurofeedbackThe session will be done on an individual basis. The sham group will receive neurofeedback training from an artificially generated random feedback signal. | Behavioural | Sham neurofeedback |
Primary outcome
Functional Connectivity Change Between Right Anterior Insular (rAI) and Right Superior Temporal Sulcus (rSTS) Within Visit1
Time frame: Immediately post-intervention during Visit 1 (day 1)
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.
2 secondary outcomes
Changes in Brief State Rumination Inventory (BSRI) Total Score From Pre- to Post-Intervention at Visit 1
Time frame: 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
Time frame: From baseline at Visit 1 (Day 1) to follow-up at Visit 2 (1 week after Visit 1)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active neurofeedback in people with Depressive Disorder, Major, run by Laureate Institute for Brain Research, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Functional Connectivity Change Between Right Anterior Insular (rAI) and Right Superior Temporal Sulcus (rSTS) Within Visit1 (time frame: Immediately post-intervention during Visit 1 (day 1)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2026.