Heart Coherence Training on Vascular Ehlers-Danlos Syndrome Patients

• ClinicalTrials.gov Identifier: NCT05994664
• Recruitment Status: Not yet recruiting
• First Posted: August 16, 2023
• Last Update Posted: January 24, 2024
• Sponsor: Baylor College of Medicine
• Collaborator: Southern Star Research Pty Ltd.
• Information provided by (Responsible Party): Shaine Morris, Baylor College of Medicine

Study Description

Brief Summary:

Vascular Ehlers-Danlos Syndrome (VEDS) is caused by pathogenic variants of the COL3A1 gene, resulting abnormal Type III collagen protein. This impacts the body's connective tissue and makes people with VEDS at high risk of spontaneous aortic and arterial rupture, pneumothorax, and hollow organ perforation across the age spectrum. Given this risk and high potential for lethality, VEDS is considered the most severe type of Ehlers-Danlos Syndrome. In addition, many patients experience chronic pain and fatigue, sleep disturbances, and mental health challenges. As is the case for many patients with chronic illness, stress, anxiety, and depression are often present over the course of the disease. Despite the antecedent, stress and anxiety trigger a sympathetic nervous system (SNS) response in the body, which, over a period of time, can have detrimental effects both physiologically and psychologically for patients. Recent studies have begun to use biofeedback techniques to teach patients non-pharmacological strategies for managing their autonomic nervous system. One such program, Heartmath®, has been successful in helping patients lower stress, anxiety, and systolic blood pressure. This pilot trial was established to assess the effectiveness of a virtually based heart coherence program in a population with a chronic aortopathy in an effort to establish a larger, multi-provider program that also encompasses other cardiovascular populations.

Condition or disease	Intervention/treatment	Phase
Vascular Ehlers-Danlos Syndrome	Other: Heartmath Intervention; Other: Control Group	Not Applicable

Detailed Description:

Vascular Ehlers Danlos Syndrome (VEDS) is caused by pathogenic variants of the COL3A1 gene, resulting abnormal Type III collagen protein. This impacts the body's connective tissue and makes people with VEDS at high risk of spontaneous aortic and arterial rupture, pneumothorax, and hollow organ perforation across the age spectrum. Given this risk and high potential for lethality, VEDS is considered the most severe type of Ehlers-Danlos Syndrome. In addition, many patients experience chronic pain and fatigue, sleep disturbances, and mental health challenges. As is the case for many patients with chronic illness, stress, anxiety, and depression are often present over the course of the disease. Despite the antecedent, stress and anxiety trigger a sympathetic nervous system (SNS) response in the body, which, over a period of time, can have detrimental effects both physiologically and psychologically for patients. For patients with already compromised cardiovascular systems, the dysregulation of their nervous system can potentially be detrimental to their mental and physiological health, as well as their overall quality of life.

Recent studies have begun to use biofeedback techniques to teach patients non-pharmacological strategies for managing their autonomic nervous system. One such program, Heartmath®, has been successful in helping patients lower stress, anxiety, and systolic blood pressure.

Our primary aim of this study is to evaluate the effects of an 8 week, virtually-based heart coherence training program (HCTP) with the use of wearable, biofeedback technology. The goal is to perform a randomized-controlled pilot study to assess effect estimates on multiple outcomes in an effort to establish a foundation for a larger, longitudinal trial.

The objective is to:

1. Randomize 20 patients with Vascular Ehlers-Danlos Syndrome from ages 12 -45 years to current status and care (controls) versus a biofeedback intervention of additional training and advancement on HeartMath techniques, then
2. Allow the control group subjects to then have access to materials related to the techniques that were taught to the HMI group to allow for therapeutic equality. The investigators will then compare outcomes between both the intervention and control groups, and between the baseline and post-intervention states. Specific outcome measures will include ambulatory blood pressure, heart rate variability, coherence ratio, mean heart rate, quality of life/mental health assessment: health-related quality of life, depression and anxiety screening scales.

Our hypothesis is that individuals with VEDS undergoing a supervised HCTP will demonstrate improvements in ambulatory blood pressure, heart rate variability, and mental health survey measures.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Trial will have two parallel groups and randomization will be performed at a 1:1 allocation.
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: The Effects Of Heart Coherence Training On Patients With Vascular Ehlers-Danlos Syndrome (HEARTMATH)
• Estimated Study Start Date: March 1, 2024
• Estimated Primary Completion Date: June 1, 2026
• Estimated Study Completion Date: January 1, 2028

Arms and Interventions

Arm	Intervention/treatment
Experimental: Intervention; Group of up to 20 patients will be randomly allocated into an experimental group at a 1:1 ratio intervention to controls. The experimental group will receive all of the preliminary outcome screening with the additional 10-15 minutes of training and advancement on HeartMath techniques as well as continued written and video reinforcement.	Other: Heartmath Intervention; The participants will all complete baseline surveys and paperwork including signed consent, psychometric surveys, demographic survey, and a brief, open-ended questionnaire about their feelings about living with VEDS. During the initial visit for the intervention group the same assessment will be included, however, they will also receive 10-15 of instruction on a basic Heartmath technique. Group participants will be asked to complete 5-10 minutes of HeartMath techniques 2x daily. Participants from both groups will have weekly virtual sessions that include the 3-step Protocol HRV assessment. However, each week the intervention group will receive an addition 10-15 minutes of training and advancement on HeartMath techniques as well as continued written and video reinforcement.
Placebo Comparator: Control; Group of up to 20 patients will be randomly allocated into a control group at a 1:1 ratio for intervention to controls. The control group will receive all of the preliminary outcome screening and will have weekly virtual sessions that include the 3-step Protocol HRV assessment. After the CG has completed 8 weeks, they will then have access to materials related to the techniques that were taught to the HMI group to allow for therapeutic equality.	Other: Control Group; The participants will all complete baseline surveys and paperwork including signed consent, psychometric surveys, demographic survey, and a brief, open-ended questionnaire about their feelings about living with VEDS. The initial visit will include an HRV assessment using the HeartMath sensor via the 3-step Protocol developed by the HeartMath Institute. Participants from both groups will have weekly virtual sessions that include the 3-step Protocol HRV assessment. After the CG has completed 8 weeks, they will then have access to materials related to the techniques that were taught to the HMI group to allow for therapeutic equality.

Outcome Measures

Primary Outcome Measures :

1. Percent Change in Mean Overall Systolic Blood Pressure [ Time Frame: 3 Months ]
   Comparing baseline to post-intervention overall systolic blood pressure in percent

Secondary Outcome Measures :

1. Mean systolic blood pressure [ Time Frame: 3 Month ]
   mmHg, range 70-200, both low and high are abnormal, goal is age, sex and height-based, goal 10-50 percentile
2. Mean Diastolic blood pressure [ Time Frame: 3 Month ]
   mmHg, range 20-150, both low and high are abnormal, goal is age, sex and height-based, goal 10-50 percentile
3. Nocturnal systolic blood pressure [ Time Frame: 3 Month ]
   mmHg, range 70-200, both low and high are abnormal, goal is age, sex and height-based, goal 10-50 percentile, nocturnal reading
4. Nocturnal Diastolic blood pressure [ Time Frame: 3 Month ]
   mmHg, range 20-150, both low and high are abnormal, goal is age, sex and height-based, goal 10-50 percentile, nocturnal reading
5. Diurnal Systolic blood pressure [ Time Frame: 3 Month ]
   mmHg, range 70-200, both low and high are abnormal, goal is age, sex and height-based, goal 10-50 percentile, diurnal reading
6. Diurnal Diastolic blood pressure [ Time Frame: 3 Month ]
   mmHg, range 20-150, both low and high are abnormal, goal is age, sex and height-based, goal 10-50 percentile, diurnal reading
7. Daily Systolic blood pressure [ Time Frame: 3 Month ]
   mmHg, range 70-200, both low and high are abnormal, goal is age, sex and height-based, goal 10-50 percentile
8. Daily Diastolic blood pressure [ Time Frame: 3 Month ]
   mmHg, range 20-150, both low and high are abnormal, goal is age, sex and height-based, goal 10-50 percentile
9. Coherence Percentage [ Time Frame: 3 Months ]
   Between 0.04-0.24 Hz (3-15 cycles per min), The more stable and regular the heart rhythm frequency is the higher the coherence. Percent ranges from 0.5 Basic good beginner level, 1.0 Good, 2.0 Very Good, 3.0+ Excellent. The higher the percentage the better.
10. Heart rate variability [ Time Frame: 3 Months ]
    Consists of beat to beat changes in heart rate measured by values below 50 ms are classified as unhealthy, 50-100 ms have compromised health, and above 100 ms are classified as healthy.
11. Mean Heart Rate [ Time Frame: Measured at baseline and follow up visit (at 12 weeks) ]
    Measured for 24 hrs, range of 60-100 bpm
12. Nocturnal Heart Rate [ Time Frame: Measured at baseline and follow up visit (at 12 weeks) ]
    Adolescent: 50-90 bpm and Adult: 40-50 bpm, measured for 24 hours
13. Diurnal Heart Rate [ Time Frame: Measured at baseline and follow up visit (at 12 weeks) ]
    Adolescent: 60-100 bmp and Adult: 60-100 bmp, measured for 24 hours
14. Quality of Life Scale (QOLS) (ages 19-21 y) [ Time Frame: 3 Months ]
    16 items, each with 7 point Likert, higher is worse
15. Pediatric Quality of Life Scale (PedsQL) scale scores [ Time Frame: 3 Months ]
    reported in 3 domains, each reported on Likert scale, scaled to 0-100 scale, lower is worse
16. GAD-7 [ Time Frame: 3 Months ]
    Seven-item questionnaire that detects generalized anxiety disorder and the severity of the anxiety. Total score for the seven items ranges from 0 to 21. The higher the score the worse; cut off score is 8.
17. PSC [ Time Frame: 3 Months ]
    The Pediatric Symptom Checklist (PSC) is a 35 item questionnaire that helps identify and assess changes in emotional and behavioral problems in children. A positive score on the PSC or Y-PSC suggests the need for further evaluation by a qualified health. PSC-35-Youth, English & Spanish cut off score is, 30 or higher. In a Mexican-American sample, a cutoff score of 12 was shown to be most sensitive.
18. PSC-Y [ Time Frame: 3 Months ]
    The Pediatric Symptom Checklist (PSC) is a 35 item questionnaire that helps identify and assess changes in emotional and behavioral problems in children. A positive score on the PSC or Y-PSC suggests the need for further evaluation by a qualified health. PSC-35-Youth, English & Spanish cut off score is, 30 or higher. In a Mexican-American sample, a cutoff score of 12 was shown to be most sensitive.PSC Subscales:Attention Problems, Internalizing Problems, Externalizing Problems
19. PSC-Y Attention Subscale [ Time Frame: 3 Months ]

    The Pediatric Symptom Checklist (PSC) is a 35 item questionnaire that helps identify and assess changes in emotional and behavioral problems in children. A positive score on the PSC or Y-PSC suggests the need for further evaluation by a qualified health. PSC-35-Youth, English & Spanish cut off score is, 30 or higher. In a Mexican-American sample, a cutoff score of 12 was shown to be most sensitive.

    PSC Subscales:Attention Problems Subscale: Children with subscores greater than or equal to 7 usually have significant impairments in attention.

20. PSC-Y Internalizing Problems Subscale [ Time Frame: 3 Months ]

    The Pediatric Symptom Checklist (PSC) is a 35 item questionnaire that helps identify and assess changes in emotional and behavioral problems in children. A positive score on the PSC or Y-PSC suggests the need for further evaluation by a qualified health. PSC-35-Youth, English & Spanish cut off score is, 30 or higher. In a Mexican-American sample, a cutoff score of 12 was shown to be most sensitive.

    PSC Subscales:

    Internalizing Problems Subscale: Children with subscores greater than or equal to 5 usually have significant impairments with anxiety or depression.

21. PSC-Y Externalizing Problems Subscale [ Time Frame: 3 Months ]

    The Pediatric Symptom Checklist (PSC) is a 35 item questionnaire that helps identify and assess changes in emotional and behavioral problems in children. A positive score on the PSC or Y-PSC suggests the need for further evaluation by a qualified health. PSC-35-Youth, English & Spanish cut off score is, 30 or higher. In a Mexican-American sample, a cutoff score of 12 was shown to be most sensitive.

    PSC Subscales:

    Externalizing Problems Subscale: Children with subscores greater than or equal to 7 usually have significant problems with conduct.

22. PROMIS Pediatric Self- Reported Psychological Stress [ Time Frame: 3 Months ]
    PROMIS scores have a mean of 50 and standard deviation (SD) of 10 in a referent population. On the T-score metric, A score of 40 is one SD lower than the mean of the reference population. A score of 60 is one SD higher than the mean of the reference population. Better health is a lower score and worse health scores higher.
23. PROMIS Parent Proxy Reported Psychological Stress- Parent Proxy [ Time Frame: 3 Months ]
    PROMIS scores have a mean of 50 and standard deviation (SD) of 10 in a referent population. On the T-score metric, A score of 40 is one SD lower than the mean of the reference population. A score of 60 is one SD higher than the mean of the reference population. Higher score is worse health.
24. The PROMIS Adult Depression SF v1.0 8a [ Time Frame: 3 Months ]

    Adult measure is the 8-item PROMIS Depression Short Form v1.0 8a questionnaire that assesses the pure domain of depression in individuals age 18 and older.

    A higher PROMIS T-score represents more of the concept being measured. For negatively-worded concepts like depression, a T-score of 60 is one SD worse than average. By comparison, a depression T-score of 40 is one SD better than average.

25. The PROMIS Pediatric Depression SF V2.0 8a [ Time Frame: 3 Months ]

    The PROMIS Short Form v2.0 - Depression 8a questionnaire includes 8 questions related to depressed mood in the past 7 days for ages 8-17.

    A higher PROMIS T-score represents more of the concept being measured. For negatively-worded concepts like depression, a T-score of 60 is one SD worse than average. By comparison, a depression T-score of 40 is one SD better than average.

26. The PROMIS Parent Proxy Depression SF v2.0 6a [ Time Frame: 3 Months ]

    The PROMIS Short Form v2.0 - Depression 6a questionnaire includes 6 questions related to depressed mood in the past 7 days for parents serving as proxy reporters for their child (youth ages 5-17).

    A higher PROMIS T-score represents more of the concept being measured. For negatively-worded concepts like depression, a T-score of 60 is one SD worse than average. By comparison, a depression T-score of 40 is one SD better than average.

Eligibility Criteria

• Ages Eligible for Study: 12 Years to 45 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Participants must be diagnosed with Vascular Ehlers-Danlos Syndrome verified by a mutation of the COL3A1 gene
• Ages 12-45 year at the time of enrollment
• Access to a smartphone as well as an additional device with camera and microphone
• Stable internet access
• English speaking

Exclusion Criteria:

• Non-English speakers
• Any conditions or developmental delays limiting the ability to utilize technology or follow directions.

Contacts and Locations

Contacts

Contact: Shaine A Morris, MD, MPH; 832-826-5692; shainem@bcm.edu

Contact: Jennifer Bogardus, PT, MPT, PhD; 713-794-2070; jennifer.bogardus@utah.edu

Locations

United States, Texas

Texas Children's Hospital

Houston, Texas, United States, 77030

Sponsors and Collaborators

Baylor College of Medicine

Southern Star Research Pty Ltd.

Investigators

• Principal Investigator: Shaine A Morris, MD, MPH; Baylor College of Medicine

More Information

• Responsible Party: Shaine Morris, Associate Professor, Pediatrics-Cardiology, Baylor College of Medicine
• ClinicalTrials.gov Identifier: NCT05994664
• Other Study ID Numbers: H-53424
• First Posted: August 16, 2023
• Last Update Posted: January 24, 2024
• Last Verified: January 2024

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Shaine Morris, Baylor College of Medicine:

Cardiovascular; Mental Health; Heart Rate Variability

Additional relevant MeSH terms:

Ehlers-Danlos Syndrome; Ehlers-Danlos Syndrome, Type IV; Syndrome; Disease; Pathologic Processes; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Hematologic Diseases; Skin Abnormalities; Congenital Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Collagen Diseases; Connective Tissue Diseases; Skin Diseases; Aortic Dissection; Dissection, Blood Vessel; Aneurysm