StressComBiNeNCT06208787
Neurofeedback-Assisted Mindfulness Techniques to Reduce Symptoms of Mental Distress
A study testing Neurofeedback training in people with Stress, run by KU Leuven at 1 site in Belgium.
Trial summary
Neurofeedback training, based on operant conditioning techniques, involves the measurement and conscious regulation of specific neural parameters through participant-specific feedback. This technique has gained recognition for its role in efficiently altering brain activity. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Stress
- What is being tested?
- Neurofeedback training
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteBelgium
- Study dates
- 8 Jan 2024to 8 Aug 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Provided written informed consent;
- Dutch or English speaking;
- Experience mild to severe stress symptoms (as measured by a score between 15 and 33 on the Stress Subscale of the DASS-21).
Who cannot join
- History of psychotropic medication usage in the past six months;
- Substantial experience with meditative practices (including but not limited to mindfulness, yoga, tai chi, or other similar practices) by meeting any of the following criteria:
- Participant has participated in a multi-day meditation retreat or program during the past year;
- Participant engages in meditative practices on a weekly basis or more frequently, for at least six consecutive weeks, within six month prior to the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Combining Novel Bio-Neurofeedback Techniques With Mindfulness-Based Interventions to Reduce Symptoms of Mental Distress
Neurofeedback training, based on operant conditioning techniques, involves the measurement and conscious regulation of specific neural parameters through participant-specific feedback. This technique has gained recognition for its role in efficiently altering brain activity. Among its various applications, neurofeedback training is noted for its ability to facilitate meditative practice and enhance stress regulation abilities. However, most neurofeedback studies focus on modulating isolated brainwaves and overlook how brainwaves interact across frequencies. To address this gap, the present study will evaluate an intervention that combines meditation techniques with a novel cross-frequency neurofeedback training to enhance the outcomes of meditative practice for stress regulation.
Previous research has established that brain rhythms exhibit interactive patterns, forming harmonic and non-harmonic relationships to respectively facilitate and preclude cross-frequency coupling. Harmonic relationships are essential for the synchronization of oscillations, a process necessary for coordinating complex neural and physiological activities. In contrast, non-harmonic relationships result in a highly desynchronized state characterized by reduced neural and physiological coordination, typically observed during cognitive restful periods. In this regard, prior studies have demonstrated a link between an increased occurrence of non-harmonic alpha-theta ratios and mindfulness meditation.
Recent research has shown the possibility of upregulating the incidence of non-harmonic alpha-theta ratios during mindfulness meditation in a single-session neurofeedback training context. However, the impact of long-term training on stress regulation abilities remains unclear. The current study addresses this gap by conducting a 10-session neurofeedback training focused on upregulating the incidence of non-harmonic alpha-theta ratios during focused attention meditation. The primary aim of this study is to determine the effectiveness of this training in assisting mindfulness practice and improving stress regulation as assessed by a range of neurophysiological, psychological, and biological outcomes.
Read the detailed description
The present study is a single-blind, randomized-controlled clinical trial involving 80 healthy, meditation-naïve adults. All participants will be randomly assigned to either take part in experimental neurofeedback training or control (sham) neurofeedback training. Each training consists of 10 training sessions, with a frequency of 2 sessions per week (i.e., 5 weeks total training duration).
During each neurofeedback training session, participants will sit in front of a computer screen in a dimly lit room. Each training session will start and finish with a self-report mood assessment (POMS) and a 2-minute neural resting-state recording. In-between, participants will take part in 10 consecutive 2-minute neurofeedback trials. During these trials, participants are instructed to close their eyes and focus their attention on a specific point of their body (i.e., an anchor point). Simultaneously, neural recordings will be made, and reinforcing auditory cues will be presented upon the measurement of non-harmonic ratios between alpha and theta rhythms at the Pz channel. Participants are informed that the feedback sounds serve as positive feedback for their ability to engage in a neurophysiological state associated with meditative practice for stress regulation, and that this sound will assist their body in self-regulating to sustain this desired state. The sham training will be indistinguishable from the experimental biofeedback training for the participants involved. However, during the sham training, auditory cues will be unrelated to the participant's underlying brain activity, presented at random timepoints and therefore, no specific training can occur. After every two training trials, participants will be asked to indicate their levels of focus, sleepiness, and relaxation.
The investigators will measure psychological, neurophysiological, and biological mental health outcomes before the start of the training (T0), following the end of the training (T1), and again at the 5-week follow-up (T2).
During these three assessment points, participants will complete self-report questionnaires on emotional distress (DASS), mindfulness skills (CHIME), perceived stress (PSS), repetitive negative thinking (PTQ), and sleep quality (PSQI). Next, neurophysiological measurements will be made during a 5-minute eyes-closed resting state recording, during a 10-minute eyes-closed focused attention meditation, and during eyes-closed stress induction (3 min) and recovery (17 out of 57 min). Stress will be induced by utilizing the cold pressor task procedure which involves the participant submerging their hand into cold water (0-2°C) for a duration of three minutes while being perceived to be recorded by a video camera. Cortisol samples will be obtained right before the stress induction (T0), during the expected cortisol peak (T0 + 20 minutes) and after a recovery period (T0 + 60 minutes).
In addition, the day following each assessment session, participants will be asked to apply mobile health patches for ambulant recording of their cardiac activity for a duration of 24 hours. At the same time, stress reactivity in daily life will be assessed using the experience sampling method. To this end, participants will be prompted on their smartphones at semi-random moments during the daytime to indicate how they are feeling for 4 consecutive days (10 prompts per day). Finally, in the morning of each assessment day, participants will collect salivary samples for the assessment of cortisol and oxytocin levels.
- Conditions
- Stress
- Being tested
- Neurofeedback training, Sham Training
- Keywords
- neurofeedback, mindfulness, stress, cross-frequency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neurofeedback trainingBehavioural
Neurofeedback training involving auditory feedback upon measurement of non-harmonic alpha-theta ratios during focused attention meditation
Sham TrainingBehavioural
Sham neurofeedback involving auditory feedback at random timepoints during focused attention meditation such that no learning can take place
| Study group | Role | What they receive |
|---|---|---|
| Experimental group | Experimental | Individuals assigned to this group will receive the experimental neurofeedback training Receives: Behavioral: Neurofeedback training |
| Control group | Sham comparator | Individuals assigned to this group will receive the sham neurofeedback training Receives: Behavioral: Sham Training |
What is being measured
The primary outcome is the main question the study is designed to answer.
occurrence of non-harmonic alpha-theta ratios at rest
EEG recording
Measured: pre-intervention (week 0), post-intervention (week 6), follow-up (week 11)
occurrence of non-harmonic alpha-theta ratios during meditation
EEG recording
Measured: pre-intervention (week 0), post-intervention (week 6), follow-up (week 11)
occurrence of non-harmonic alpha-theta ratios during stress induction
EEG recording
Measured: pre-intervention (week 0), post-intervention (week 6), follow-up (week 11)
occurrence of non-harmonic alpha-theta ratios during stress recovery
EEG recording
Measured: pre-intervention (week 0), post-intervention (week 6), follow-up (week 11)
self-reported levels of emotional distress
DASS questionnaire
Measured: pre-intervention (week 0), post-intervention (week 6), follow-up (week 11)
Secondary outcomes (4)
self-reported levels of mindfulness skills
CHIME questionnaire
Measured: pre-intervention (week 0), post-intervention (week 6), follow-up (week 11)
self-reported levels of perceived stress
PSS questionnaire
Measured: pre-intervention (week 0), post-intervention (week 6), follow-up (week 11)
self-reported levels of repetitive negative thinking
PTQ questionnaire
Measured: pre-intervention (week 0), post-intervention (week 6), follow-up (week 11)
self-reported levels of sleep quality
PSQI questionnaire
Measured: pre-intervention (week 0), post-intervention (week 6), follow-up (week 11)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2024
- Study start8 Jan 2024
- Primary completion8 Aug 2025
- Study completion8 Aug 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for StressStudies of the same condition, open and under way.
- More trials run by KU LeuvenThe sponsor's other registered studies.
- 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
- Single blind
- Who is masked
- Participant
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- KU Leuven
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kaat Alaerts, KU Leuven
- Investigators
- Kaat Alaerts, PhD, Principal investigator, KU Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06208787
- Sponsor's protocol ID
- S68049
- Acronym
- ComBiNe
- Status last verified
- Feb 2026
- First submitted
- 21 Dec 2023
- Last updated
- 6 Feb 2026
- Results posted
- No
- 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 6 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combining Novel Bio-Neurofeedback Techniques With Mindfulness-Based Interventions to Reduce Symptoms of Mental Distress
- ClinicalTrials.gov ID
- NCT06208787
- Acronym / sponsor ID
- ComBiNe / S68049
- Conditions
- Stress
- Keywords
- neurofeedback, mindfulness, stress, cross-frequency
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- KU LeuvenUniversity, hospital or other
- Study start
- 8 Jan 2024 (actual)
- Primary completion
- 8 Aug 2025 (actual)
- Study completion
- 8 Aug 2025 (actual)
- First posted
- 17 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Neurofeedback training, based on operant conditioning techniques, involves the measurement and conscious regulation of specific neural parameters through participant-specific feedback. This technique has gained recognition for its role in efficiently altering brain activity. Among its various applications, neurofeedback training is noted for its ability to facilitate meditative practice and enhance stress regulation abilities. However, most neurofeedback studies focus on modulating isolated brainwaves and overlook how brainwaves interact across frequencies. To address this gap, the present study will evaluate an intervention that combines meditation techniques with a novel cross-frequency neurofeedback training to enhance the outcomes of meditative practice for stress regulation.
Previous research has established that brain rhythms exhibit interactive patterns, forming harmonic and non-harmonic relationships to respectively facilitate and preclude cross-frequency coupling. Harmonic relationships are essential for the synchronization of oscillations, a process necessary for coordinating complex neural and physiological activities. In contrast, non-harmonic relationships result in a highly desynchronized state characterized by reduced neural and physiological coordination, typically observed during cognitive restful periods. In this regard, prior studies have demonstrated a link between an increased occurrence of non-harmonic alpha-theta ratios and mindfulness meditation.
Recent research has shown the possibility of upregulating the incidence of non-harmonic alpha-theta ratios during mindfulness meditation in a single-session neurofeedback training context. However, the impact of long-term training on stress regulation abilities remains unclear. The current study addresses this gap by conducting a 10-session neurofeedback training focused on upregulating the incidence of non-harmonic alpha-theta ratios during focused attention meditation. The primary aim of this study is to determine the effectiveness of this training in assisting mindfulness practice and improving stress regulation as assessed by a range of neurophysiological, psychological, and biological outcomes.
Detailed description
The present study is a single-blind, randomized-controlled clinical trial involving 80 healthy, meditation-naïve adults. All participants will be randomly assigned to either take part in experimental neurofeedback training or control (sham) neurofeedback training. Each training consists of 10 training sessions, with a frequency of 2 sessions per week (i.e., 5 weeks total training duration).
During each neurofeedback training session, participants will sit in front of a computer screen in a dimly lit room. Each training session will start and finish with a self-report mood assessment (POMS) and a 2-minute neural resting-state recording. In-between, participants will take part in 10 consecutive 2-minute neurofeedback trials. During these trials, participants are instructed to close their eyes and focus their attention on a specific point of their body (i.e., an anchor point). Simultaneously, neural recordings will be made, and reinforcing auditory cues will be presented upon the measurement of non-harmonic ratios between alpha and theta rhythms at the Pz channel. Participants are informed that the feedback sounds serve as positive feedback for their ability to engage in a neurophysiological state associated with meditative practice for stress regulation, and that this sound will assist their body in self-regulating to sustain this desired state. The sham training will be indistinguishable from the experimental biofeedback training for the participants involved. However, during the sham training, auditory cues will be unrelated to the participant's underlying brain activity, presented at random timepoints and therefore, no specific training can occur. After every two training trials, participants will be asked to indicate their levels of focus, sleepiness, and relaxation.
The investigators will measure psychological, neurophysiological, and biological mental health outcomes before the start of the training (T0), following the end of the training (T1), and again at the 5-week follow-up (T2).
During these three assessment points, participants will complete self-report questionnaires on emotional distress (DASS), mindfulness skills (CHIME), perceived stress (PSS), repetitive negative thinking (PTQ), and sleep quality (PSQI). Next, neurophysiological measurements will be made during a 5-minute eyes-closed resting state recording, during a 10-minute eyes-closed focused attention meditation, and during eyes-closed stress induction (3 min) and recovery (17 out of 57 min). Stress will be induced by utilizing the cold pressor task procedure which involves the participant submerging their hand into cold water (0-2°C) for a duration of three minutes while being perceived to be recorded by a video camera. Cortisol samples will be obtained right before the stress induction (T0), during the expected cortisol peak (T0 + 20 minutes) and after a recovery period (T0 + 60 minutes).
In addition, the day following each assessment session, participants will be asked to apply mobile health patches for ambulant recording of their cardiac activity for a duration of 24 hours. At the same time, stress reactivity in daily life will be assessed using the experience sampling method. To this end, participants will be prompted on their smartphones at semi-random moments during the daytime to indicate how they are feeling for 4 consecutive days (10 prompts per day). Finally, in the morning of each assessment day, participants will collect salivary samples for the assessment of cortisol and oxytocin levels.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental group | Experimental | Behavioral: Neurofeedback trainingIndividuals assigned to this group will receive the experimental neurofeedback training |
| Control group | Sham comparator | Behavioral: Sham TrainingIndividuals assigned to this group will receive the sham neurofeedback training |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Provided written informed consent;
- Dutch or English speaking;
- Experience mild to severe stress symptoms (as measured by a score between 15 and 33 on the Stress Subscale of the DASS-21).
Key exclusion criteria (4 listed)
- History of psychotropic medication usage in the past six months;
- Substantial experience with meditative practices (including but not limited to mindfulness, yoga, tai chi, or other similar practices) by meeting any of the following criteria:
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 |
|---|---|---|
| Neurofeedback trainingNeurofeedback training involving auditory feedback upon measurement of non-harmonic alpha-theta ratios during focused attention meditation | Behavioural | Experimental group |
| Sham TrainingSham neurofeedback involving auditory feedback at random timepoints during focused attention meditation such that no learning can take place | Behavioural | Control group |
Primary outcome
occurrence of non-harmonic alpha-theta ratios at rest
Time frame: pre-intervention (week 0), post-intervention (week 6), follow-up (week 11)
EEG recording
occurrence of non-harmonic alpha-theta ratios during meditation
Time frame: pre-intervention (week 0), post-intervention (week 6), follow-up (week 11)
EEG recording
occurrence of non-harmonic alpha-theta ratios during stress induction
Time frame: pre-intervention (week 0), post-intervention (week 6), follow-up (week 11)
EEG recording
occurrence of non-harmonic alpha-theta ratios during stress recovery
Time frame: pre-intervention (week 0), post-intervention (week 6), follow-up (week 11)
EEG recording
self-reported levels of emotional distress
Time frame: pre-intervention (week 0), post-intervention (week 6), follow-up (week 11)
DASS questionnaire
4 secondary outcomes
self-reported levels of mindfulness skills
Time frame: pre-intervention (week 0), post-intervention (week 6), follow-up (week 11)
self-reported levels of perceived stress
Time frame: pre-intervention (week 0), post-intervention (week 6), follow-up (week 11)
self-reported levels of repetitive negative thinking
Time frame: pre-intervention (week 0), post-intervention (week 6), follow-up (week 11)
self-reported levels of sleep quality
Time frame: pre-intervention (week 0), post-intervention (week 6), follow-up (week 11)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2026.
- 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.
Kaat Alaerts, PhD principal investigator
KU Leuven
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Neurofeedback training in people with Stress, run by KU Leuven at 1 site in Belgium.
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 3 inclusion and 4 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: finished, as of the sponsor's last update on 6 Feb 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 Belgium. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
occurrence of non-harmonic alpha-theta ratios at rest (time frame: pre-intervention (week 0), post-intervention (week 6), follow-up (week 11)). The study lists 5 primary outcomes in all. 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 6 Feb 2026.