xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05994664</url>
    </required_header>
    <id_info>
      <org_study_id>H-53424</org_study_id>
      <nct_id>NCT05994664</nct_id>
    </id_info>
    <brief_title>Heart Coherence Training on Vascular Ehlers-Danlos Syndrome Patients</brief_title>
    <official_title>The Effects Of Heart Coherence Training On Patients With Vascular Ehlers-Danlos Syndrome (HEARTMATH)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Baylor College of Medicine</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Southern Star Research Pty Ltd.</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Baylor College of Medicine</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Vascular Ehlers-Danlos Syndrome (VEDS) is caused by pathogenic variants of the COL3A1 gene,&#xD;
        resulting abnormal Type III collagen protein. This impacts the body's connective tissue and&#xD;
        makes people with VEDS at high risk of spontaneous aortic and arterial rupture, pneumothorax,&#xD;
        and hollow organ perforation across the age spectrum. Given this risk and high potential for&#xD;
        lethality, VEDS is considered the most severe type of Ehlers-Danlos Syndrome. In addition,&#xD;
        many patients experience chronic pain and fatigue, sleep disturbances, and mental health&#xD;
        challenges. As is the case for many patients with chronic illness, stress, anxiety, and&#xD;
        depression are often present over the course of the disease. Despite the antecedent, stress&#xD;
        and anxiety trigger a sympathetic nervous system (SNS) response in the body, which, over a&#xD;
        period of time, can have detrimental effects both physiologically and psychologically for&#xD;
        patients. Recent studies have begun to use biofeedback techniques to teach patients&#xD;
        non-pharmacological strategies for managing their autonomic nervous system. One such program,&#xD;
        Heartmath®, has been successful in helping patients lower stress, anxiety, and systolic blood&#xD;
        pressure. This pilot trial was established to assess the effectiveness of a virtually based&#xD;
        heart coherence program in a population with a chronic aortopathy in an effort to establish a&#xD;
        larger, multi-provider program that also encompasses other cardiovascular populations.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Vascular Ehlers Danlos Syndrome (VEDS) is caused by pathogenic variants of the COL3A1 gene,&#xD;
        resulting abnormal Type III collagen protein. This impacts the body's connective tissue and&#xD;
        makes people with VEDS at high risk of spontaneous aortic and arterial rupture, pneumothorax,&#xD;
        and hollow organ perforation across the age spectrum. Given this risk and high potential for&#xD;
        lethality, VEDS is considered the most severe type of Ehlers-Danlos Syndrome. In addition,&#xD;
        many patients experience chronic pain and fatigue, sleep disturbances, and mental health&#xD;
        challenges. As is the case for many patients with chronic illness, stress, anxiety, and&#xD;
        depression are often present over the course of the disease. Despite the antecedent, stress&#xD;
        and anxiety trigger a sympathetic nervous system (SNS) response in the body, which, over a&#xD;
        period of time, can have detrimental effects both physiologically and psychologically for&#xD;
        patients. For patients with already compromised cardiovascular systems, the dysregulation of&#xD;
        their nervous system can potentially be detrimental to their mental and physiological health,&#xD;
        as well as their overall quality of life.&#xD;
  &#xD;
        Recent studies have begun to use biofeedback techniques to teach patients non-pharmacological&#xD;
        strategies for managing their autonomic nervous system. One such program, Heartmath®, has&#xD;
        been successful in helping patients lower stress, anxiety, and systolic blood pressure.&#xD;
  &#xD;
        Our primary aim of this study is to evaluate the effects of an 8 week, virtually-based heart&#xD;
        coherence training program (HCTP) with the use of wearable, biofeedback technology. The goal&#xD;
        is to perform a randomized-controlled pilot study to assess effect estimates on multiple&#xD;
        outcomes in an effort to establish a foundation for a larger, longitudinal trial.&#xD;
  &#xD;
        The objective is to:&#xD;
  &#xD;
          1. Randomize 20 patients with Vascular Ehlers-Danlos Syndrome from ages 12 -45 years to&#xD;
             current status and care (controls) versus a biofeedback intervention of additional&#xD;
             training and advancement on HeartMath techniques, then&#xD;
  &#xD;
          2. Allow the control group subjects to then have access to materials related to the&#xD;
             techniques that were taught to the HMI group to allow for therapeutic equality. The&#xD;
             investigators will then compare outcomes between both the intervention and control&#xD;
             groups, and between the baseline and post-intervention states. Specific outcome measures&#xD;
             will include ambulatory blood pressure, heart rate variability, coherence ratio, mean&#xD;
             heart rate, quality of life/mental health assessment: health-related quality of life,&#xD;
             depression and anxiety screening scales.&#xD;
  &#xD;
        Our hypothesis is that individuals with VEDS undergoing a supervised HCTP will demonstrate&#xD;
        improvements in ambulatory blood pressure, heart rate variability, and mental health survey&#xD;
        measures.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">September 1, 2027</completion_date>
    <primary_completion_date type="Anticipated">September 1, 2025</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>Trial will have two parallel groups and randomization will be performed at a 1:1 allocation.</intervention_model_description>
      <primary_purpose>Other</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Percent Reduction in Mean Overall Systolic Blood Pressure</measure>
      <time_frame>3 Months</time_frame>
      <description>Meaningful 5% reduction in overall systolic blood pressure</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Mean systolic blood pressure</measure>
      <time_frame>3 Month</time_frame>
      <description>mmHg, range 70-200, both low and high are abnormal, goal is age, sex and height-based, goal 10-50 percentile</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mean Diastolic blood pressure</measure>
      <time_frame>3 Month</time_frame>
      <description>mmHg, range 20-150, both low and high are abnormal, goal is age, sex and height-based, goal 10-50 percentile</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Nocturnal systolic blood pressure</measure>
      <time_frame>3 Month</time_frame>
      <description>mmHg, range 70-200, both low and high are abnormal, goal is age, sex and height-based, goal 10-50 percentile, nocturnal reading</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Nocturnal Diastolic blood pressure</measure>
      <time_frame>3 Month</time_frame>
      <description>mmHg, range 20-150, both low and high are abnormal, goal is age, sex and height-based, goal 10-50 percentile, nocturnal reading</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Diurnal Systolic blood pressure</measure>
      <time_frame>3 Month</time_frame>
      <description>mmHg, range 70-200, both low and high are abnormal, goal is age, sex and height-based, goal 10-50 percentile, diurnal reading</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Diurnal Diastolic blood pressure</measure>
      <time_frame>3 Month</time_frame>
      <description>mmHg, range 20-150, both low and high are abnormal, goal is age, sex and height-based, goal 10-50 percentile, diurnal reading</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Daily Systolic blood pressure</measure>
      <time_frame>3 Month</time_frame>
      <description>mmHg, range 70-200, both low and high are abnormal, goal is age, sex and height-based, goal 10-50 percentile</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Daily Diastolic blood pressure</measure>
      <time_frame>3 Month</time_frame>
      <description>mmHg, range 20-150, both low and high are abnormal, goal is age, sex and height-based, goal 10-50 percentile</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Coherence Percentage</measure>
      <time_frame>3 Months</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Heart rate variability</measure>
      <time_frame>3 Months</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mean Heart Rate</measure>
      <time_frame>Measured at baseline and follow up visit (at 12 weeks)</time_frame>
      <description>Measured for 24 hrs, range of 60-100 bpm</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Nocturnal Heart Rate</measure>
      <time_frame>Measured at baseline and follow up visit (at 12 weeks)</time_frame>
      <description>Adolescent: 50-90 bpm and Adult: 40-50 bpm, measured for 24 hours</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Diurnal Heart Rate</measure>
      <time_frame>Measured at baseline and follow up visit (at 12 weeks)</time_frame>
      <description>Adolescent: 60-100 bmp and Adult: 60-100 bmp, measured for 24 hours</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Quality of Life Scale (QOLS) (ages 19-21 y)</measure>
      <time_frame>3 Months</time_frame>
      <description>16 items, each with 7 point Likert, higher is worse</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pediatric Quality of Life Scale (PedsQL) scale scores</measure>
      <time_frame>3 Months</time_frame>
      <description>reported in 3 domains, each reported on Likert scale, scaled to 0-100 scale, lower is worse</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>GAD-7</measure>
      <time_frame>3 Months</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PSC</measure>
      <time_frame>3 Months</time_frame>
      <description>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 &amp; Spanish cut off score is, 30 or higher. In a Mexican-American sample, a cutoff score of 12 was shown to be most sensitive.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PSC-Y</measure>
      <time_frame>3 Months</time_frame>
      <description>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 &amp; 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</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PSC-Y Attention Subscale</measure>
      <time_frame>3 Months</time_frame>
      <description>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 &amp; Spanish cut off score is, 30 or higher. In a Mexican-American sample, a cutoff score of 12 was shown to be most sensitive.&#xD;
  PSC Subscales:Attention Problems Subscale: Children with subscores greater than or equal to 7 usually have significant impairments in attention.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PSC-Y Internalizing Problems Subscale</measure>
      <time_frame>3 Months</time_frame>
      <description>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 &amp; Spanish cut off score is, 30 or higher. In a Mexican-American sample, a cutoff score of 12 was shown to be most sensitive.&#xD;
  PSC Subscales:&#xD;
  Internalizing Problems Subscale: Children with subscores greater than or equal to 5 usually have significant impairments with anxiety or depression.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PSC-Y Externalizing Problems Subscale</measure>
      <time_frame>3 Months</time_frame>
      <description>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 &amp; Spanish cut off score is, 30 or higher. In a Mexican-American sample, a cutoff score of 12 was shown to be most sensitive.&#xD;
  PSC Subscales:&#xD;
  Externalizing Problems Subscale: Children with subscores greater than or equal to 7 usually have significant problems with conduct.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PROMIS Pediatric Self- Reported Psychological Stress</measure>
      <time_frame>3 Months</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PROMIS Parent Proxy Reported Psychological Stress- Parent Proxy</measure>
      <time_frame>3 Months</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The PROMIS Adult Depression SF v1.0 8a</measure>
      <time_frame>3 Months</time_frame>
      <description>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.&#xD;
  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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The PROMIS Pediatric Depression SF V2.0 8a</measure>
      <time_frame>3 Months</time_frame>
      <description>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.&#xD;
  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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The PROMIS Parent Proxy Depression SF v2.0 6a</measure>
      <time_frame>3 Months</time_frame>
      <description>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).&#xD;
  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.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">40</enrollment>
    <condition>Vascular Ehlers-Danlos Syndrome</condition>
    <arm_group>
      <arm_group_label>Intervention</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>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.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>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.</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Heartmath Intervention</intervention_name>
      <description>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.</description>
      <arm_group_label>Intervention</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Control Group</intervention_name>
      <description>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.</description>
      <arm_group_label>Control</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Participants must be diagnosed with Vascular Ehlers-Danlos Syndrome verified by a&#xD;
               mutation of the COL3A1 gene&#xD;
  &#xD;
            -  Ages 12-45 year at the time of enrollment&#xD;
  &#xD;
            -  Access to a smartphone as well as an additional device with camera and microphone&#xD;
  &#xD;
            -  Stable internet access&#xD;
  &#xD;
            -  English speaking&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Non-English speakers&#xD;
  &#xD;
            -  Any conditions or developmental delays limiting the ability to utilize technology or&#xD;
               follow directions.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>12 Years</minimum_age>
      <maximum_age>45 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Shaine A Morris, MD, MPH</last_name>
      <role>Principal Investigator</role>
      <affiliation>Baylor College of Medicine</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Shaine A Morris, MD, MPH</last_name>
      <phone>832-826-5692</phone>
      <email>shainem@bcm.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Jennifer Bogardus, PT, MPT, PhD</last_name>
      <phone>713-794-2070</phone>
      <email>jennifer.bogardus@utah.edu</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Texas Children's Hospital</name>
        <address>
          <city>Houston</city>
          <state>Texas</state>
          <zip>77030</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 9, 2023</study_first_submitted>
    <study_first_submitted_qc>August 9, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 16, 2023</study_first_posted>
    <last_update_submitted>August 9, 2023</last_update_submitted>
    <last_update_submitted_qc>August 9, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 16, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Baylor College of Medicine</investigator_affiliation>
      <investigator_full_name>Shaine Morris</investigator_full_name>
      <investigator_title>Associate Professor, Pediatrics-Cardiology</investigator_title>
    </responsible_party>
    <keyword>Cardiovascular</keyword>
    <keyword>Mental Health</keyword>
    <keyword>Heart Rate Variability</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Ehlers-Danlos Syndrome</mesh_term>
      <mesh_term>Ehlers-Danlos Syndrome, Type IV</mesh_term>
      <mesh_term>Syndrome</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05994664
  org study id: H-53424
  nct id: NCT05994664
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  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.
  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.
  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.
  primary purpose: Other
  masking: None (Open Label)
  measure: Percent Reduction in Mean Overall Systolic Blood Pressure
  time frame: 3 Months
  description: Meaningful 5% reduction in overall systolic blood pressure
  measure: Mean systolic blood pressure
  time frame: 3 Month
  description: mmHg, range 70-200, both low and high are abnormal, goal is age, sex and height-based, goal 10-50 percentile
  measure: Mean Diastolic blood pressure
  time frame: 3 Month
  description: mmHg, range 20-150, both low and high are abnormal, goal is age, sex and height-based, goal 10-50 percentile
  measure: Nocturnal systolic blood pressure
  time frame: 3 Month
  description: mmHg, range 70-200, both low and high are abnormal, goal is age, sex and height-based, goal 10-50 percentile, nocturnal reading
  measure: Nocturnal Diastolic blood pressure
  time frame: 3 Month
  description: mmHg, range 20-150, both low and high are abnormal, goal is age, sex and height-based, goal 10-50 percentile, nocturnal reading
  measure: Diurnal Systolic blood pressure
  time frame: 3 Month
  description: mmHg, range 70-200, both low and high are abnormal, goal is age, sex and height-based, goal 10-50 percentile, diurnal reading
  measure: Diurnal Diastolic blood pressure
  time frame: 3 Month
  description: mmHg, range 20-150, both low and high are abnormal, goal is age, sex and height-based, goal 10-50 percentile, diurnal reading
  measure: Daily Systolic blood pressure
  time frame: 3 Month
  description: mmHg, range 70-200, both low and high are abnormal, goal is age, sex and height-based, goal 10-50 percentile
  measure: Daily Diastolic blood pressure
  time frame: 3 Month
  description: mmHg, range 20-150, both low and high are abnormal, goal is age, sex and height-based, goal 10-50 percentile
  measure: Coherence Percentage
  time frame: 3 Months
  description: 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.
  measure: Heart rate variability
  time frame: 3 Months
  description: 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.
  measure: Mean Heart Rate
  time frame: Measured at baseline and follow up visit (at 12 weeks)
  description: Measured for 24 hrs, range of 60-100 bpm
  measure: Nocturnal Heart Rate
  time frame: Measured at baseline and follow up visit (at 12 weeks)
  description: Adolescent: 50-90 bpm and Adult: 40-50 bpm, measured for 24 hours
  measure: Diurnal Heart Rate
  time frame: Measured at baseline and follow up visit (at 12 weeks)
  description: Adolescent: 60-100 bmp and Adult: 60-100 bmp, measured for 24 hours
  measure: Quality of Life Scale (QOLS) (ages 19-21 y)
  time frame: 3 Months
  description: 16 items, each with 7 point Likert, higher is worse
  measure: Pediatric Quality of Life Scale (PedsQL) scale scores
  time frame: 3 Months
  description: reported in 3 domains, each reported on Likert scale, scaled to 0-100 scale, lower is worse
  measure: GAD-7
  time frame: 3 Months
  description: 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.
  measure: PSC
  time frame: 3 Months
  description: 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.
  measure: PSC-Y
  time frame: 3 Months
  description: 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
  measure: PSC-Y Attention Subscale
  time frame: 3 Months
  description: 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.
  measure: PSC-Y Internalizing Problems Subscale
  time frame: 3 Months
  description: 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.
  measure: PSC-Y Externalizing Problems Subscale
  time frame: 3 Months
  description: 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.
  measure: PROMIS Pediatric Self- Reported Psychological Stress
  time frame: 3 Months
  description: 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.
  measure: PROMIS Parent Proxy Reported Psychological Stress- Parent Proxy
  time frame: 3 Months
  description: 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.
  measure: The PROMIS Adult Depression SF v1.0 8a
  time frame: 3 Months
  description: 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.
  measure: The PROMIS Pediatric Depression SF V2.0 8a
  time frame: 3 Months
  description: 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.
  measure: The PROMIS Parent Proxy Depression SF v2.0 6a
  time frame: 3 Months
  description: 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.
  arm group label: Intervention
  arm group type: Experimental
  description: 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.
  arm group label: Control
  arm group type: Placebo Comparator
  description: 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.
  intervention type: Other
  intervention name: Heartmath Intervention
  description: 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.
  arm group label: Intervention
  intervention type: Other
  intervention name: Control Group
  description: 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.
  arm group label: Control
  criteria: 
  gender: All
  minimum age: 12 Years
  maximum age: 45 Years
  healthy volunteers: No
  last name: Shaine A Morris, MD, MPH
  role: Principal Investigator
  affiliation: Baylor College of Medicine
  last name: Shaine A Morris, MD, MPH
  phone: 832-826-5692
  email: shainem@bcm.edu
  last name: Jennifer Bogardus, PT, MPT, PhD
  phone: 713-794-2070
  email: jennifer.bogardus@utah.edu
  facility: 
  country: United States
  responsible party type: Principal Investigator
  investigator affiliation: Baylor College of Medicine
  investigator full name: Shaine Morris
  investigator title: Associate Professor, Pediatrics-Cardiology
  mesh term: Ehlers-Danlos Syndrome
  mesh term: Ehlers-Danlos Syndrome, Type IV
  mesh term: Syndrome