Stress Management Program

Examining the Immediate and Training Effects of Regular Stress Reduction Practices on Psychophysiological Markers of Anxiety

This study will test the immediate and long term (post 4 weeks of daily practice) effectiveness of two breathwork practices, cyclic sighing and box breathing, in comparison to hypnosis and an audiobook about stress, on psychological and physiological variables.

Study Overview

• Status: Recruiting
• Conditions: Stress; Anxiety
• Intervention / Treatment: Behavioral: Cyclic Sighing Breathing; Behavioral: Box Breathing; Behavioral: Hypnosis; Behavioral: Audiobook

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Bita Nouriani, MS; Phone Number: (650) 723-8479; Email: bita@stanford.edu
• Study Contact Backup: Name: Cassidy Kinderman, BA; Phone Number: ‪(650) 260-8766‬; Email: ckinder@stanford.edu

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Recruiting
      • Psychiatry & Behavioral Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18 or older
• No contraindications to MRI imaging (like ferromagnetic metal in their body)

Exclusion Criteria:

• Pregnant or planning to get pregnant during study participation.
• Not able or willing to come to research location twice for MRI assessments

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cyclic Sighing Breathing; Ten minutes a day of active breathwork practice for 28 days delivered remotely through a video link. Participants will also practice 10 minutes of active breathwork during the 2 MRI assessments, one before the start of the 28 days, and one after the completion of the 28 days.	Behavioral: Cyclic Sighing Breathing; Participants are instructed to be seated or lying down, and can keep their eyes open or closed throughout the 10 minutes of the breathing practice during the 28 days. Participants are instructed to keep their eyes closed when practicing the 10 minutes of the cyclic sighing during the 2 MRI assessments. The cyclic sighing protocol consists of a breathing pattern that involves inhaling deeply, starting abdominally, inhaling through the nose until lungs feel comfortably filled, immediately followed by a second shorter inhale, also through the nose, to maximally inflate the lungs. Then participants are instructed to slowly exhale through the mouth until their lungs feel empty. This cycle is repeated for 10 minutes.
Experimental: Box Breathing; Ten minutes a day of active breathwork practice for 28 days delivered remotely through a video link. Participants will also practice 10 minutes of active breathwork during the 2 MRI assessments, one before the start of the 28 days, and one after the completion of the 28 days.	Behavioral: Box Breathing; Participants are instructed to be seated or lying down, and can keep their eyes open or closed throughout the 10 minutes of the breathing during the 28 days. Participants are instructed to keep their eyes closed when practicing the 10 minutes of the box breathing during the 2 MRI assessments. The CO2 tolerance test is done at baseline to determine their comfort level with the duration of each side of the box during box breathing. The box breathing protocol consists of a four-part breathing technique. The practice involves breathing through the nose in four equally timed parts: inhale, hold, exhale, and hold again, forming a 'box' of breaths (e.g. 4 sec inhale, 4 sec hold, 4 sec exhale, 4 sec hold).This cycle is repeated for 10 minutes.
Experimental: Hypnosis; Ten minutes a day of hypnosis practice for 28 days delivered remotely through an audio link. Participants will also practice 10 minutes of hypnosis during the 2 MRI assessments, one before the start of the 28 days, and one after the completion of the 28 days	Behavioral: Hypnosis; Participants are instructed to sit comfortably or lie down during the 28 day at home practice (Participants will be lying down in the scanner during the 2 MRIs). Then participants are asked to look up, slowly close their eyes, take a deep breath, slowly exhale, and let their body float, and then to imagine floating in a bath, a lake, a hot tub, or floating in space. Participants are then asked to picture an imaginary screen and visualize a place where it would naturally feel comfortable and relaxed. The participants then divide the screen in half and picture on the left side one thing that is causing them stress, with the rule that no matter what the participant picture, to keep their body comfortable and relaxed. Then on the right side of the screen the participants are asked to picture one thing that can be done about the problem on the left. At the end the participant will be guided to come out of the state of hypnosis. This exercise will take 10 minutes.
Active Comparator: Audiobook on Stress; Ten minutes a day of listening to sections of an audiobook about stress for 28 days (passive listening) delivered remotely through an audio link. Participants will also listen to the 10 minute segments during the 2 MRI assessments, one before the start of the 28 days, and one after the completion of the 28 days.	Behavioral: Audiobook; Participants are instructed to be seated or lying down, and can keep eyes open or closed throughout the 10 minutes of listening to the audiobook during the 28 days. Participants are instructed to keep their eyes closed during the 2 MRI assessments.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neural Activation	As measured for example by Fractional amplitude of low-frequency fluctuation (fALFF) signal, assessed using functional Magnetic Resonance Imaging (fMRI).	Baseline Scan (Day 0) and and Follow-up Scan (From day 29 up to 4 weeks later, depending on the Scan scheduling availability)
State Anxiety scale score	The State-Trait Anxiety Inventory (STAI) is an instrument for measuring anxiety in adults. It has 2 scales: State Anxiety (S-Anxiety) and Trait Anxiety (T-Anxiety). The S-Anxiety scale measures anxiety due to temporary conditions, and the T-Anxiety measures anxiety on a general or more long-standing scale. The S-Anxiety is a 20-item scale; each item yields a score of 1 to 4. Scores on the STAI S-Anxiety scale increase in response to physical danger and psychological stress and decrease as a result of relaxation training.	Immediate: Baseline Scan (Day 0) and Follow-up Scan (from day 29 up to 4 weeks later, depending on the Scan scheduling availability); Daily: from Baseline (Day 0) to a day prior to Endpoint (Day 28)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respiratory Rate	Daily respiratory rate (RR) will be collected by WHOOP Strap 2.0, a wearable photoplethysmography (PPG) wrist sensor.	Daily from Baseline (Day 0) to a day prior to Endpoint (Day 28)
Heart Rate Variability	Heart rate variability (HRV) will be measured in two modalities. Immediate continuous HRV, collected during resting-state MRI scans, will be measured by a wearable photoplethysmography (PPG) finger sensor. Daily HRV over the 28-day training period (RMSSD) will be collected by WHOOP Strap 2.0, a wearable PPG wrist sensor.	Immediate: Baseline Scan (Day 0) and Follow-up Scan (From day 29 up to 4 weeks later, depending on the Scan scheduling availability); Daily: from Baseline (Day 0) to a day prior to Endpoint (Day 28)

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: David Spiegel, MD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: July 19, 2024
• First Submitted That Met QC Criteria: July 24, 2024
• First Posted (Actual): July 30, 2024

Study Record Updates

• Last Update Posted (Actual): February 23, 2026
• Last Update Submitted That Met QC Criteria: February 19, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Anxiety; Stress; Heart Rate Variability; Sleep; Hypnosis; fMRI; Mood; Brain Activity; Respiratory Rate; Physiology; Breathwork; Box Breathing; Cyclic Sighing
• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders; Therapeutics; Mind-Body Therapies; Complementary Therapies; Psychotherapy; Behavioral Disciplines and Activities; Technology, Industry, and Agriculture; Technology; Audiovisual Aids; Educational Technology; Hypnosis; Sound Recordings
• Other Study ID Numbers: 72131

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No