Autonomic Dysfunction, Postural Orthostatic Tachycardia Syndrome, Postural Tachycardia Syndrome, POTS - Postural Orthostatic Tachycardia Syndrome
Conditions
Brief summary
The purpose of this study is to determine if nVNS will decrease autonomic symptom intensity (COMPASS-31 and Child Functional Disability Inventory) in adolescent patients with postural orthostatic tachycardia syndrome (POTS) in comparison to standard recovery STEPS management.
Detailed description
Project purpose: The investigators will study the use of non invasive vagal nerve stimulation in newly diagnosed adolescent patients with POTS to see if symptom management improves over 2 months. Surveys will include COMPASS-31. Child Functional Disability Inventory, and PHQ-9. Patient logs will evaluate headache frequency, exercise duration and VNS use. Research objectives: The investigators hypothesize that: Primary Aim 1. Use of noninvasive vagal nerve stimulation will decrease autonomic symptom intensity compared to control group. Primary Aim 2. Use of noninvasive vagal nerve stimulator will improve child function. Primary Aim 3. Heart rate elevation measured by head up tilt table test will decrease in the treatment group compared to the control group. Secondary goals include: Secondary Aim 1: To determine if utilization of noninvasive vagal nerve stimulation influences headache frequency Secondary Aim 2: Determine if utilization of noninvasive vagal nerve stimulation will influence weekly duration of aerobic exercise. Secondary Aim 3: Determine if utilization of noninvasive vagal nerve stimulator results in significant side effects, particularly depression, in adolescent patients.
Interventions
DEVICEGammaCore intervention
Use of the vagal nerve stimulator, GammaCore, on the right side of the neck for two 2 minute stimulations performed 3 times a day
OTHERSTEPS management protocol
STEPS is the acronym for the standard management program for our patients with POTS. It includes liberal use of salt, taking in 90-100 ounces of fluid, gradually increasing the duration of aerobic exercise, possible use of one of two prescription medications (metoprolol, and midodrine), and encouragement to set priority and goals
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Intervention model description
Half of the patient population will be randomized to standard management only. The other half of the population will be randomized to standard management plus use of the vagal nerve stimulator
Eligibility
Sex/Gender
ALL
Age
12 Years to 19 Years
Healthy volunteers
Yes
Inclusion criteria
1. Patient's age 12-19 years of age 2. Newly diagnosed POTS at Mayo Clinic in Rochester 3. Head up tilt table test results in a heart rate increase of 40 or more bpm 4. Consent is able to be obtained appropriately per age
Exclusion criteria
1. POTS patients with orthostatic hypotension 2. POTS patients with vasovagal syncope 3. Use of medications other than midodrine or metoprolol 4. Inability to independently utilize the GammaCore device 5. Inability to independently complete surveys or patient logs 6. Patients receiving hormonal therapy other than birth control 7. Pregnancy 8. Prior neck surgery 9. Metallic implant present 10. Cardiac disorder 11. Presence of an eating disorder 12. Use of a feeding tube
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Change in Composite Autonomic Symptom Score (COMPASS-31) | Baseline; 8 Weeks | The change in COMPASS-31 score from baseline to 8 weeks. COMPASS-31 measures autonomic dysfunction in patients with neurodegenerative diseases. It consists of 31 patient-reported questions assessing various symptoms, including orthostatic intolerance, vasomotor symptoms, and gastrointestinal issues. Total scores range from 0 to 100, with higher scores indicating more severe symptoms. |
| The Change in Child Functional Disability Inventory Scores | Baseline; 8 Weeks | The change in Child Functional Disability Inventory scores from baseline to eight weeks. The Child Functional Disability Inventory assesses the physical and psychosocial functioning of children due to their physical health. It consists of 15 items that measure activity limitations due to being sick or not feeling well. The total scores range from 0 to 60 with higher scores indicating greater perceived functional disability. |
| The Change in Heart Rate (Beats Per Minute) in Head up Tilt Table Tests | Baseline; 8 Weeks | The change in heart rate, measured in beats per minute (BPM), in the head up tilt table test (HUTT) from baseline to 8 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Number of Headaches Experienced by Adolescent Patients With POTS | Baseline; 8 Weeks | The change in the number of headaches from baseline to 8 weeks experienced by adolescent patients with POTS. |
| Change in Exercise Duration (Minutes) in Adolescent Patients With POTS | Baseline; 8 Weeks | The change in the exercise duration (minutes) in adolescent patients with POTS from baseline to 8 weeks. |
| Change in PHQ-9 Scores in Adolescent Patients With POTS | Baseline; 8 Weeks | The change in the Patient Health Questionnaire 9-item (PHQ-9) scale score from baseline to 8 weeks. PHQ-9 is used to assess severity of depression. Scoring is calculated by assigning scores of 0, 1, 2, and 3 to the response categories, respectively, of not at all, several days, more than half the days, and nearly every day. Total score ranges from 0 to 27 where 0 is no depression, 1-4 is minimal depression, 5-9 is mild depression, 10-14 is moderate depression, and 15-19 is moderately severe depression and 20-27 severe depression. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standard Postural Orthostatic Tachycardia Syndrome Management/ STEPS The General Pediatric and Adolescent Medicine providers at Mayo Clinic utilized a specific management program for their patients with Postural Orthostatic Tachycardia Syndrome utilizing the acronym STEPS. S is for liberal intake of salt, T is for drinking 90-100 ounces/day of fluid, E is for slowly and gradually improve continuous aerobic exercise duration to a goal of 50 minute most days of the week, P is for possible utilization of 1 of two prescription medications (metoprolol or midodrine), and S is for setting priorities and goals such as encouraging good sleep hygiene, attendance at school, social interactions, and counseling.
STEPS management protocol: STEPS is the acronym for the standard management program for our patients with POTS. It includes liberal use of salt, taking in 90-100 ounces of fluid, gradually increasing the duration of aerobic exercise, possible use of one of two prescription medications (metoprolol, and midodrine), and encouragement to set priority and goals | 20 |
| STEPS + GammaCore Intervention (Noninvasive Vagal Nerve Stimulation) Utilization of STEPS management goals plus the addition of non invasive vagal nerve stimulators for two 2 minutes of intervention performed three times a day.
GammaCore intervention: Use of the vagal nerve stimulator, GammaCore, on the right side of the neck for two 2 minute stimulations performed 3 times a day
STEPS management protocol: STEPS is the acronym for the standard management program for our patients with POTS. It includes liberal use of salt, taking in 90-100 ounces of fluid, gradually increasing the duration of aerobic exercise, possible use of one of two prescription medications (metoprolol, and midodrine), and encouragement to set priority and goals | 20 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Standard Postural Orthostatic Tachycardia Syndrome Management/ STEPS | STEPS + GammaCore Intervention (Noninvasive Vagal Nerve Stimulation) | Total |
|---|---|---|---|
| Age, Continuous | 15 years STANDARD_DEVIATION 3 | 16 years STANDARD_DEVIATION 3 | 15 years STANDARD_DEVIATION 3 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment United States | 20 participants | 20 participants | 40 participants |
| Sex: Female, Male Female | 17 Participants | 17 Participants | 34 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 4 / 20 | 9 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
The Change in Child Functional Disability Inventory Scores
The change in Child Functional Disability Inventory scores from baseline to eight weeks. The Child Functional Disability Inventory assesses the physical and psychosocial functioning of children due to their physical health. It consists of 15 items that measure activity limitations due to being sick or not feeling well. The total scores range from 0 to 60 with higher scores indicating greater perceived functional disability.
Time frame: Baseline; 8 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Postural Orthostatic Tachycardia Syndrome management/ STEPS | The Change in Child Functional Disability Inventory Scores | -2.92 score on a scale | Standard Deviation 8.6 |
| STEPS + GammaCore Intervention (noninvasive vagal nerve stimulation) | The Change in Child Functional Disability Inventory Scores | -3.40 score on a scale | Standard Deviation 11.76 |
Primary
The Change in Composite Autonomic Symptom Score (COMPASS-31)
The change in COMPASS-31 score from baseline to 8 weeks. COMPASS-31 measures autonomic dysfunction in patients with neurodegenerative diseases. It consists of 31 patient-reported questions assessing various symptoms, including orthostatic intolerance, vasomotor symptoms, and gastrointestinal issues. Total scores range from 0 to 100, with higher scores indicating more severe symptoms.
Time frame: Baseline; 8 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Postural Orthostatic Tachycardia Syndrome management/ STEPS | The Change in Composite Autonomic Symptom Score (COMPASS-31) | -5.40 score on a scale | Standard Deviation 6.82 |
| STEPS + GammaCore Intervention (noninvasive vagal nerve stimulation) | The Change in Composite Autonomic Symptom Score (COMPASS-31) | -5.94 score on a scale | Standard Deviation 10.89 |
Primary
The Change in Heart Rate (Beats Per Minute) in Head up Tilt Table Tests
The change in heart rate, measured in beats per minute (BPM), in the head up tilt table test (HUTT) from baseline to 8 weeks.
Time frame: Baseline; 8 Weeks
Population: Everyone had a baseline head up tilt table test. The repeat tilt table test was voluntary and resulted in fewer patients participating in this repeat test. The reason we made this voluntary is that many participants live far away and return for a repeat head up tilt table is inconvenient and costly.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard Postural Orthostatic Tachycardia Syndrome management/ STEPS | The Change in Heart Rate (Beats Per Minute) in Head up Tilt Table Tests | Baseline | 47.50 Beats per Minute (BPM) | Standard Deviation 6.45 |
| Standard Postural Orthostatic Tachycardia Syndrome management/ STEPS | The Change in Heart Rate (Beats Per Minute) in Head up Tilt Table Tests | 8 Weeks | 42.50 Beats per Minute (BPM) | Standard Deviation 7 |
| STEPS + GammaCore Intervention (noninvasive vagal nerve stimulation) | The Change in Heart Rate (Beats Per Minute) in Head up Tilt Table Tests | Baseline | 58.14 Beats per Minute (BPM) | Standard Deviation 28.94 |
| STEPS + GammaCore Intervention (noninvasive vagal nerve stimulation) | The Change in Heart Rate (Beats Per Minute) in Head up Tilt Table Tests | 8 Weeks | 40.14 Beats per Minute (BPM) | Standard Deviation 14.35 |
Secondary
Change in Exercise Duration (Minutes) in Adolescent Patients With POTS
The change in the exercise duration (minutes) in adolescent patients with POTS from baseline to 8 weeks.
Time frame: Baseline; 8 Weeks
Population: One patient in the standard POTS management/STEPS arm and two patients in the STEPS + GammaCore arm did not fill out the patient log at week 8 that documented exercise duration in minutes. Due to this, no data exists for week 8 for these patients.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Standard Postural Orthostatic Tachycardia Syndrome management/ STEPS | Change in Exercise Duration (Minutes) in Adolescent Patients With POTS | Baseline | 25.00 Minutes |
| Standard Postural Orthostatic Tachycardia Syndrome management/ STEPS | Change in Exercise Duration (Minutes) in Adolescent Patients With POTS | 8 Weeks | 32.50 Minutes |
| STEPS + GammaCore Intervention (noninvasive vagal nerve stimulation) | Change in Exercise Duration (Minutes) in Adolescent Patients With POTS | 8 Weeks | 17.90 Minutes |
| STEPS + GammaCore Intervention (noninvasive vagal nerve stimulation) | Change in Exercise Duration (Minutes) in Adolescent Patients With POTS | Baseline | 21.40 Minutes |
Secondary
Change in PHQ-9 Scores in Adolescent Patients With POTS
The change in the Patient Health Questionnaire 9-item (PHQ-9) scale score from baseline to 8 weeks. PHQ-9 is used to assess severity of depression. Scoring is calculated by assigning scores of 0, 1, 2, and 3 to the response categories, respectively, of not at all, several days, more than half the days, and nearly every day. Total score ranges from 0 to 27 where 0 is no depression, 1-4 is minimal depression, 5-9 is mild depression, 10-14 is moderate depression, and 15-19 is moderately severe depression and 20-27 severe depression.
Time frame: Baseline; 8 Weeks
Population: Seven patients in the Device group and seven patients in the Control group had incomplete data for the PHQ-9 scores (missing either the baseline PHQ-9 survey or the final PHQ-8 at 8 weeks).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Postural Orthostatic Tachycardia Syndrome management/ STEPS | Change in PHQ-9 Scores in Adolescent Patients With POTS | 0.23 score on a scale | Standard Deviation 3.56 |
| STEPS + GammaCore Intervention (noninvasive vagal nerve stimulation) | Change in PHQ-9 Scores in Adolescent Patients With POTS | -3.39 score on a scale | Standard Deviation 4.54 |
Secondary
Change in the Number of Headaches Experienced by Adolescent Patients With POTS
The change in the number of headaches from baseline to 8 weeks experienced by adolescent patients with POTS.
Time frame: Baseline; 8 Weeks
Population: One patient in the standard POTS management/STEPS arm and two patients in the STEPS + GammaCore arm did not fill out the patient log at week 8 that documented the number of headaches they experienced. Due to this, no data exists for week 8 for these patients.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Standard Postural Orthostatic Tachycardia Syndrome management/ STEPS | Change in the Number of Headaches Experienced by Adolescent Patients With POTS | Baseline | 1.00 Headaches |
| Standard Postural Orthostatic Tachycardia Syndrome management/ STEPS | Change in the Number of Headaches Experienced by Adolescent Patients With POTS | 8 Weeks | 1.20 Headaches |
| STEPS + GammaCore Intervention (noninvasive vagal nerve stimulation) | Change in the Number of Headaches Experienced by Adolescent Patients With POTS | Baseline | 1.30 Headaches |
| STEPS + GammaCore Intervention (noninvasive vagal nerve stimulation) | Change in the Number of Headaches Experienced by Adolescent Patients With POTS | 8 Weeks | 0.40 Headaches |