AnxietyBREATH-4NCT07621042
Comparative Effects of Four Brief Breathwork and Mindfulness Interventions on Anxiety and Psychological Flexibility: A 4-Arm RCT
A study testing Box Breathing, Cyclic Sighing and Mindfulness AH Exhalation in people with Anxiety and Psychological Flexibility, run by Valencian International University (VIU).
Trial summary
This four-arm, single-blind randomized controlled trial examines the effects of four brief daily 5-minute practices over 28 days on psychological flexibility and physiological variables in Spanish-speaking adults. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Anxiety, Psychological Flexibility, Stress
- What is being tested?
- Box Breathing, Cyclic Sighing and Mindfulness AH Exhalation
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 240 participants
- Where
- No sites listed yet
- Study dates
- Jan 2027to May 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age between 18 and 65 years (inclusive)
- Native Spanish speaker or fluent in Spanish (sufficient to understand audio instructions and complete psychometric questionnaires)
- Stable internet access and an electronic device (smartphone, tablet, or computer)
- Ability to provide informed consent and commitment to the 31-day protocol and 2-month follow-up
Who cannot join
- Active diagnosis of severe or chronic respiratory disease that prevents safe performance of breathing exercises (e.g., advanced COPD, severe uncontrolled asthma, cystic fibrosis)
- Current diagnosis of severe psychiatric disorder (e.g., psychotic spectrum disorders, acute-phase bipolar disorder, severe major depression with suicidal risk)
- Any acute medical condition contraindicated for voluntary alteration of breathing patterns
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Effect of Brief Breathwork and Mindfulness Interventions on Anxiety, Psychological Flexibility and Physiological Variables in Spanish-Speaking University Students: a Four-Arm Randomized Controlled Trial
This four-arm, single-blind randomized controlled trial examines the effects of four brief daily 5-minute practices over 28 days on psychological flexibility and physiological variables in Spanish-speaking adults. Participants will be randomly assigned to one of four groups: Box Breathing, Cyclic Sighing, Mindfulness focused on exhalation with the syllable "AH", or Conscious Cyclic Sighing. Outcomes include state and trait anxiety (STAI), positive and negative affect (PANAS), psychological flexibility (MPFI-24, Psy-Flex), and physiological variables (heart rate, respiratory rate, heart rate variability). Assessments are conducted at baseline, daily during the 28-day intervention, at post-intervention (day 31), and at 2-month follow-up.
- Conditions
- Anxiety, Psychological Flexibility, Stress
- Being tested
- Box Breathing, Cyclic Sighing, Mindfulness AH Exhalation, Mindful Cyclic Sighing
- Keywords
- breathworks, mindfulness, box breathing, cyclic sighing, heart rate variability, randomized controlled trial, Spanish-speaking
- Medical subject headings
- Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Box BreathingBehavioural
Individualized box breathing based on CO2 tolerance test. Participants perform a maximal exhale and record the duration (CO2 discard time) to determine their personal cycle interval: 3-4s (0-20s discard), 5-6s (25-45s discard), or 8-10s (50-75s+ discard). Equal-phase cycles of inhale/hold/exhale/hold repeated for 5 minutes daily. Focus on mechanical breath control only.
Cyclic SighingBehavioural
Double nasal inhalation (slow deep inhale + short top-up inhale to maximal lung capacity) followed by slow complete oral exhalation. Repeated continuously for 5 minutes daily. No attentional instructions.
Mindfulness AH ExhalationBehavioural
Focused-attention practice with eyes closed. Attention directed to forehead region between the eyes. Each exhalation accompanied by soft audible vocalization of syllable "AH". Distractions managed with internal label "thinking-thinking" followed by attention redirection. Practiced daily for 5 minutes.
Mindful Cyclic SighingBehavioural
Hybrid practice: double nasal inhalation (cyclic sighing mechanics) combined with slow exhalation vocalized as soft audible "AH". Mindfulness instructions include attention to breath sensations and use of "thinking-thinking" label upon distraction. Practiced daily for 5 minutes.
| Study group | Role | What they receive |
|---|---|---|
| Box Breathing | Experimental | Daily 5-minute box breathing with individualized timing based on a CO2 tolerance test. Participants perform a maximal exhale and record the duration; this determines their personal inhale/hold/exhale/hold intervals (3-4s, 5-6s, or 8-10s). Equal-phase cyclic breathing with exclusive focus on mechanical control and counting. Receives: Behavioral: Box Breathing |
| Cyclic Sighing | Experimental | Daily 5-minute cyclic sighing. Participants inhale slowly through the nose, then take a second shorter nasal inhale to maximally fill the lungs, followed by a slow, complete oral exhalation. This double-inhale/long-exhale pattern is repeated continuously for 5 minutes. No mindfulness or attentional instructions are given. Receives: Behavioral: Cyclic Sighing |
| Mindfulness AH Exhalation | Experimental | Daily 5-minute focused-attention mindfulness practice. Participants sit or lie down, close their eyes, and direct attention to the forehead region between the eyes. On each exhale, they softly vocalize the syllable "AH" aloud (gentle, unforced audible sound). When distracted, they use the internal label "thinking-thinking" and redirect attention to the breath and then to the forehead region. Practice continues for 5 minutes. Receives: Behavioral: Mindfulness AH Exhalation |
| Mindful Cyclic Sighing | Experimental | Daily 5-minute hybrid practice combining cyclic sighing mechanics with mindfulness instructions. Participants inhale slowly through the nose, take a second shorter nasal inhale to maximally fill the lungs, then exhale slowly while softly vocalizing the syllable "AH" aloud (gentle, unforced). Attention is directed to the breath and the sensation of release during exhalation. When distracted, participants use the internal label "thinking-thinking" and redirect attention back to the breath. Practice continues for 5 minutes. Receives: Behavioral: Mindful Cyclic Sighing |
What is being measured
The primary outcome is the main question the study is designed to answer.
State Anxiety (STAI-E)
State anxiety measured with the State-Trait Anxiety Inventory - State subscale (STAI-E). 20 items rated on a 4-point Likert scale (0-3). Higher scores indicate greater anxiety. Spanish validated version (Guillen-Riquelme \& Buela-Casal, 2011).
Measured: Baseline (Day 0), daily pre- and post-practice (Days 1-28), post-intervention (Day 31), and 2-month follow-up
Secondary outcomes (4)
Positive and Negative Affect (PANAS)
Positive and negative affect measured with the Positive and Negative Affect Schedule (PANAS). 20 items rated on a 5-point Likert scale. Two subscales: Positive Affect (PA) and Negative Affect (NA). Spanish validated version (Lopez-Gomez et al., 2015).
Measured: Baseline (Day 0), daily pre- and post-practice (Days 1-28), post-intervention (Day 31), and 2-month follow-up
Psychological Flexibility (MPFI-24)
Multidimensional psychological flexibility and inflexibility measured with the Multidimensional Psychological Flexibility Inventory short form (MPFI-24). 24 items rated on a 6-point Likert scale assessing 12 Hexaflex processes. Spanish validated version (Navarrete et al., 2024).
Measured: Baseline (Day 0), post-intervention (Day 31), and 2-month follow-up
Psychological Flexibility (Psy-Flex)
Unified psychological flexibility measured with the Psy-Flex scale. 6 items rated on a 5-point Likert scale. A modified daily version will be used during the intervention period. Spanish validated version (Navarrete et al., 2024).
Measured: Baseline (Day 0), daily (Days 1-28), post-intervention (Day 31), and 2-month follow-up
Trait Anxiety (STAI-R)
Trait anxiety measured with the State-Trait Anxiety Inventory - Trait subscale (STAI-R). 20 items rated on a 4-point Likert scale (0-3). Higher scores indicate greater trait anxiety. Spanish validated version (Guillen-Riquelme \& Buela-Casal, 2011).
Measured: Baseline (Day 0), post-intervention (Day 31), and 2-month follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2026
- Study startJan 2027 (estimated)
- Primary completionMar 2027 (estimated)
- Study completionMay 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for AnxietyStudies 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
- Model description
- Four-arm parallel-group RCT. Participants are randomly assigned 1:1:1:1 to one of four daily 5-minute breath-based practices for 28 days.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 240 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Valencian International University (VIU)
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Isaac Carmona-Rincón, Valencian International University (VIU)
- Investigators
- Isaac Carmona-Rincón, PhD, Principal investigator, Valencian International University (VIU)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07621042
- Sponsor's protocol ID
- VIU-BREATH-RCT-2026
- Acronym
- BREATH-4
- Status last verified
- Jun 2026
- First submitted
- 27 May 2026
- Last updated
- 4 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Anonymized individual participant data (IPD) and the data dictionary will be made available upon reasonable request to the principal investigator (isaac.carmona@professor.universidadviu.com). Requests will be evaluated on a case-by-case basis.
Publications
Chan AW, Boutron I, Hopewell S, Moher D, Schulz KF, Collins GS, Tunn R, Aggarwal R, Berkwits M, Berlin JA, Bhandari N, Butcher NJ, Campbell MK, Chidebe RCW, Elbourne DR, Farmer AJ, Fergusson DA, Golub RM, Goodman SN, Hoffmann TC, Ioannidis JPA, Kahan BC, Knowles RL, Lamb SE, Lewis S, Loder E, Offringa M, Ravaud P, Richards DP, Rockhold FW, Schriger DL, Siegfried NL, Staniszewska S, Taylor RS, Thabane L, Torgerson DJ, Vohra S, White IR, Hrobjartsson A. SPIRIT 2025 statement: updated guideline for protocols of randomized trials. Nat Med. 2025 Jun;31(6):1784-1792. doi: 10.1038/s41591-025-03668-w. Epub 2025 Apr 29.
PubMed 40295741Balban MY, Neri E, Kogon MM, Weed L, Nouriani B, Jo B, Holl G, Zeitzer JM, Spiegel D, Huberman AD. Brief structured respiration practices enhance mood and reduce physiological arousal. Cell Rep Med. 2023 Jan 17;4(1):100895. doi: 10.1016/j.xcrm.2022.100895. Epub 2023 Jan 10.
PubMed 36630953
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Brief Breathwork and Mindfulness Interventions on Anxiety, Psychological Flexibility and Physiological Variables in Spanish-Speaking University Students: a Four-Arm Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT07621042
- Acronym / sponsor ID
- BREATH-4 / VIU-BREATH-RCT-2026
- Conditions
- Anxiety, Psychological Flexibility, Stress
- Keywords
- breathworks, mindfulness, box breathing, cyclic sighing, heart rate variability, randomized controlled trial, Spanish-speaking
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 240 participants (estimated)
- Lead sponsor
- Valencian International University (VIU)University, hospital or other
- Study start
- Jan 2027 (estimated)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- May 2027 (estimated)
- First posted
- 2 Jun 2026 (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.
This four-arm, single-blind randomized controlled trial examines the effects of four brief daily 5-minute practices over 28 days on psychological flexibility and physiological variables in Spanish-speaking adults. Participants will be randomly assigned to one of four groups: Box Breathing, Cyclic Sighing, Mindfulness focused on exhalation with the syllable "AH", or Conscious Cyclic Sighing. Outcomes include state and trait anxiety (STAI), positive and negative affect (PANAS), psychological flexibility (MPFI-24, Psy-Flex), and physiological variables (heart rate, respiratory rate, heart rate variability). Assessments are conducted at baseline, daily during the 28-day intervention, at post-intervention (day 31), and at 2-month follow-up.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 4
- Model description
- Four-arm parallel-group RCT. Participants are randomly assigned 1:1:1:1 to one of four daily 5-minute breath-based practices for 28 days.
| Arm | Type | Receives |
|---|---|---|
| Box Breathing | Experimental | Behavioral: Box BreathingDaily 5-minute box breathing with individualized timing based on a CO2 tolerance test. Participants perform a maximal exhale and record the duration; this determines their personal inhale/hold/exhale/hold intervals (3-4s, 5-6s, or 8-10s). Equal-phase cyclic breathing with exclusive focus on mechanical control and counting. |
| Cyclic Sighing | Experimental | Behavioral: Cyclic SighingDaily 5-minute cyclic sighing. Participants inhale slowly through the nose, then take a second shorter nasal inhale to maximally fill the lungs, followed by a slow, complete oral exhalation. This double-inhale/long-exhale pattern is repeated continuously for 5 minutes. No mindfulness or attentional instructions are given. |
| Mindfulness AH Exhalation | Experimental | Behavioral: Mindfulness AH ExhalationDaily 5-minute focused-attention mindfulness practice. Participants sit or lie down, close their eyes, and direct attention to the forehead region between the eyes. On each exhale, they softly vocalize the syllable "AH" aloud (gentle, unforced audible sound). When distracted, they use the internal label "thinking-thinking" and redirect attention to the breath and then to the forehead region. Practice continues for 5 minutes. |
| Mindful Cyclic Sighing | Experimental | Behavioral: Mindful Cyclic SighingDaily 5-minute hybrid practice combining cyclic sighing mechanics with mindfulness instructions. Participants inhale slowly through the nose, take a second shorter nasal inhale to maximally fill the lungs, then exhale slowly while softly vocalizing the syllable "AH" aloud (gentle, unforced). Attention is directed to the breath and the sensation of release during exhalation. When distracted, participants use the internal label "thinking-thinking" and redirect attention back to the breath. Practice continues for 5 minutes. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age between 18 and 65 years (inclusive)
- Native Spanish speaker or fluent in Spanish (sufficient to understand audio instructions and complete psychometric questionnaires)
- Stable internet access and an electronic device (smartphone, tablet, or computer)
- Ability to provide informed consent and commitment to the 31-day protocol and 2-month follow-up
Key exclusion criteria (3 listed)
- Active diagnosis of severe or chronic respiratory disease that prevents safe performance of breathing exercises (e.g., advanced COPD, severe uncontrolled asthma, cystic fibrosis)
- Current diagnosis of severe psychiatric disorder (e.g., psychotic spectrum disorders, acute-phase bipolar disorder, severe major depression with suicidal risk)
- Any acute medical condition contraindicated for voluntary alteration of breathing patterns
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 |
|---|---|---|
| Box BreathingIndividualized box breathing based on CO2 tolerance test. Participants perform a maximal exhale and record the duration (CO2 discard time) to determine their personal cycle interval: 3-4s (0-20s discard), 5-6s (25-45s discard), or 8-10s (50-75s+ discard). Equal-phase cycles of inhale/hold/exhale/hold repeated for 5 minutes daily. Focus on mechanical breath control only. | Behavioural | Box Breathing |
| Cyclic SighingDouble nasal inhalation (slow deep inhale + short top-up inhale to maximal lung capacity) followed by slow complete oral exhalation. Repeated continuously for 5 minutes daily. No attentional instructions. | Behavioural | Cyclic Sighing |
| Mindfulness AH ExhalationFocused-attention practice with eyes closed. Attention directed to forehead region between the eyes. Each exhalation accompanied by soft audible vocalization of syllable "AH". Distractions managed with internal label "thinking-thinking" followed by attention redirection. Practiced daily for 5 minutes. | Behavioural | Mindfulness AH Exhalation |
| Mindful Cyclic SighingHybrid practice: double nasal inhalation (cyclic sighing mechanics) combined with slow exhalation vocalized as soft audible "AH". Mindfulness instructions include attention to breath sensations and use of "thinking-thinking" label upon distraction. Practiced daily for 5 minutes. | Behavioural | Mindful Cyclic Sighing |
Primary outcome
State Anxiety (STAI-E)
Time frame: Baseline (Day 0), daily pre- and post-practice (Days 1-28), post-intervention (Day 31), and 2-month follow-up
State anxiety measured with the State-Trait Anxiety Inventory - State subscale (STAI-E). 20 items rated on a 4-point Likert scale (0-3). Higher scores indicate greater anxiety. Spanish validated version (Guillen-Riquelme \& Buela-Casal, 2011).
4 secondary outcomes
Positive and Negative Affect (PANAS)
Time frame: Baseline (Day 0), daily pre- and post-practice (Days 1-28), post-intervention (Day 31), and 2-month follow-up
Psychological Flexibility (MPFI-24)
Time frame: Baseline (Day 0), post-intervention (Day 31), and 2-month follow-up
Psychological Flexibility (Psy-Flex)
Time frame: Baseline (Day 0), daily (Days 1-28), post-intervention (Day 31), and 2-month follow-up
Trait Anxiety (STAI-R)
Time frame: Baseline (Day 0), post-intervention (Day 31), and 2-month follow-up
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2026.
- Background: PubMed 40295741Chan AW, Boutron I, Hopewell S, Moher D, Schulz KF, Collins GS, Tunn R, Aggarwal R, Berkwits M, Berlin JA, Bhandari N, Butcher NJ, Campbell MK, Chidebe RCW, Elbourne DR, Farmer AJ, Fergusson DA, Golub RM, Goodman SN, Hoffmann TC, Ioannidis JPA, Kahan BC, Knowles RL, Lamb SE, Lewis S, Loder E, Offringa M, Ravaud P, Richards DP, Rockhold FW, Schriger DL, Siegfried NL, Staniszewska S, Taylor RS, Thabane L, Torgerson DJ, Vohra S, White IR, Hrobjartsson A. SPIRIT 2025 statement: updated guideline for protocols of randomized trials. Nat Med. 2025 Jun;31(6):1784-1792. doi: 10.1038/s41591-025-03668-w. Epub 2025 Apr 29.
- Background: PubMed 36630953Balban MY, Neri E, Kogon MM, Weed L, Nouriani B, Jo B, Holl G, Zeitzer JM, Spiegel D, Huberman AD. Brief structured respiration practices enhance mood and reduce physiological arousal. Cell Rep Med. 2023 Jan 17;4(1):100895. doi: 10.1016/j.xcrm.2022.100895. Epub 2023 Jan 10.
- Individual participant dataSharing planned: Yes. Anonymized individual participant data (IPD) and the data dictionary will be made available upon reasonable request to the principal investigator (isaac.carmona@professor.universidadviu.com). Requests will be evaluated on a case-by-case basis.
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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.
Isaac Carmona-Rincón, PhD principal investigator
Valencian International University (VIU)
Questions about this trial
What is this clinical trial studying?
A study testing Box Breathing, Cyclic Sighing and Mindfulness AH Exhalation in people with Anxiety and Psychological Flexibility, run by Valencian International University (VIU).
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 3 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: opening soon, as of the sponsor's last update on 4 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Isaac Carmona-Rincón, PhD (+34 618 187 325, isaac.carmona@professor.universidadviu.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
State Anxiety (STAI-E) (time frame: Baseline (Day 0), daily pre- and post-practice (Days 1-28), post-intervention (Day 31), and 2-month follow-up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07621042, which also lists 2 linked publications.
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 4 Jun 2026.