Pulmonary Arterial Hypertension, Idiopathic Pulmonary Arterial Hypertension, Heritable Pulmonary Arterial Hypertension, Associated Pulmonary Arterial Hypertension
Conditions
Keywords
Pulmonary Arterial Hypertension
Brief summary
This study proposes the use of a mobile health intervention (utilizing a smart phone app) to encourage increased exercise in PAH patients. The study will be a randomized trial to examine feasibility of an mHealth (mobile device) Fitbit Charge HR and cell phone application intervention to improve step counts and increase participants activity level as compared to no intervention. The Fitbit Charge Heart Rate (HR) monitors activity and the cell phone application provides encouragement notifications to half the subjects while the other half do not receive encouragements.
Detailed description
Patients with pulmonary arterial hypertension (PAH) have severely reduced exercise capacity and reduced quality of life. At diagnosis, most PAH patients are New York Heart Association (NYHA) functional class III with symptoms of fatigue and shortness of breath with less than ordinary activity. Physical activity confers multiple benefits relevant to PAH pathophysiology including improvements in endothelial function, energy metabolism, and right ventricular (RV) function. Increasing physical activity is highly efficacious in PAH, resulting in six-minute walk distance (6MWD) improvement that exceeds the effect of medications. The goal of this proposal is to adapt and test the feasibility of our mHealth intervention to increase physical activity in a geographically diverse PAH population. In secondary aims, we will assess conventional PAH trial outcomes (6MWD, quality of life) and physiologic mechanisms by which increasing activity may improve exercise capacity. The investigator hypothesizes that an mHealth intervention is feasible and will increase physical activity in subjects with PAH. This study proposes a randomized trial of unblinded step tracking with smart texts tracking for 12 weeks. Participants will wear a display-free triaxial accelerometer, which will continuously transmit data to a compatible smartphone (owned by 75% of our PAH population). Efficacy endpoints have been selected to mirror FDA criteria for drug approval in PAH. The following aims will be tested: Aim 1: To test the feasibility of an mHealth intervention to increase step counts in patients with PAH. Fifty PAH patients will be randomized to the mHealth intervention or usual activity for 12 weeks. The primary endpoint will be daily step count during Week 12. Secondary endpoints will assess step target achievement, daily activity time, and aerobic time. The fidelity of data collection and text transmission will also be assessed. Aim 2: To examine the effect of an mHealth intervention on exercise capacity and quality of life. Participants will complete a six minute walk test and the emPHasis-10 questionnaire at baseline and 12 weeks. The primary endpoint will be six minute walk distance. Secondary endpoints will be emPHasis-10 quality of life scale score, Borg dyspnea score, and resting heart rate. Aim 3: To examine the effect of an mHealth intervention on mechanisms of improved exercise capacity. Subjects will undergo echocardiography, blood draw, and body composition assessment. The primary endpoint will be RV longitudinal strain. Secondary endpoints will be the homeostatic model assessment of insulin resistance, lean muscle and fat mass, and B-type natriuretic peptide.
Interventions
DEVICESmartphone Text Messaging
A HIPPA compliant text messaging platform is linked to the Fitbit Application Program Interface. Real time activity data will be transmitted from the subject's smartphone to our mHealth platform via cellular network. Subjects will receive 3 texts/day in sync with their preferred morning, lunch, and evening leisure schedule (defined at enrollment). These texts will use personal, disease-specific, and provider information to deliver 2 types of messages customized to the current step count and sent in equal proportion. Messages are designed to facilitate self-awareness, reinforce step targets, and link physical activity with a reward or memorable cue.
DEVICEFitbit Charge HR
The Fitbit Charge HR tri-axial accelerometer will be used to continuously gather data on physical activity, heart rate, and sleep. This device provides feedback in units of activity (steps, stairs climbed, activity time, and exercise time) and heart rate (per second when active, per 5 seconds when inactive). It has been validated against research devices in free-living conditions and is relatively inexpensive.
Sponsors
Johns Hopkins University
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Caregiver, Investigator, Outcomes Assessor)
Masking description
Investigators are blinded. Study personnel conducting 6MWT and echo will be blinded.
Intervention model description
Randomization will occur after a two-week run-in period to improve ability to identify a true baseline step count and account for potential dropout. Participants will be assigned to either the smartphone text messaging or no smartphone text messaging arms in a random manner until 25 participants are enrolled into each arm. Permuted block randomization stratified by functional class (I/II vs. III) will be used to ensure approximate balance of treatment groups within each stratum over time. Randomization will be performed in small blocks, which vary in size. Investigators will be unaware of the size or order of the blocks. Randomization will occur through REDCap by a study coordinator. Although the texting intervention will end after Week 12, subjects in both groups will be asked to continue wearing the Fitbit Charge HR device for an additional 3 weeks to determine whether withdrawal of the texting intervention results in a reduction in step counts.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Aged 18 or older. 2. Diagnosed with idiopathic, heritable, or associated (connective tissue disease, drugs, or toxins) pulmonary arterial hypertension (PAH) according to World Health Organization consensus recommendations. 3. Stable PAH-specific medication regimen for three months prior to enrollment. Subjects with only a single diuretic adjustment in the prior three months will be included. 4. Subjects must own a Bluetooth capable modern smartphone capable of receiving and sending text messages and an active data plan.
Exclusion criteria
1. Prohibited from normal activity due to wheelchair bound status, bed bound status, reliance on a cane/walker, activity-limiting angina, activity-limiting osteoarthritis, or other condition. 2. Pregnancy. 3. Diagnosis of PAH etiology other than idiopathic, heritable, or associated. 4. Forced vital capacity \<70% predicted. 5. Functional class IV heart failure. 6. Requirement of \> 1 diuretic adjustment in the prior three months. 7. Preferred form of activity is not measured by an activity tracker (swimming, yoga, ice skating, stair master, or activities on wheels such as bicycling or rollerblading).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Daily Step Count | Baseline to 12 weeks | Change from baseline mean daily step count at week 12. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Six Minute Walk Test Distance | Baseline to 12 weeks | Change from baseline of six minute walk test distance (meters) at week 12. |
| Right Ventricle (RV) Strain | Baseline to 12 weeks | Change from baseline of RV free wall longitudinal strain at week 12. |
| Percentage of Days Participants Met Their Daily Step Count Goal | Baseline to 12 weeks | All participants were provided with an Fitbit Charge Heart Rate mobile device to monitor daily step counts, activity time, and aerobic time. The daily goal was communicated via text to the intervention group and was the baseline step count average for the control group. Increased daily goal attainment indicates increased activity level |
| Daily Aerobic Time | Baseline to 12 weeks | Change in minutes of activity per day between Week 12 and Baseline |
| Change From Baseline at Week 12 in emPHasis-10 Questionnaire Score | Baseline to 12 weeks | Quality of life was assessed using the emPHasis-10 questionnaire, a disease-specific self-administered 10-question questionnaire designed for routine assessment of health-related quality of life in pulmonary hypertension. Total score can range from 0 to 50, with higher scores indicating a worse quality of life. Change from Baseline was calculated as the value at Week 12 minus the value at Baseline. The Week 12 value was defined as the last assessment at or prior to Week 12. |
| Change From Baseline on the SF-36 Mental Component Summary (MCS) Score | Baseline to 12 weeks | SF-36 consists of 36 questions measuring 8 health domains: physical functioning, bodily pain, role limitations due to physical problems, role limitations due to emotional problems, general health perceptions, mental health, social function, and vitality. The patient's responses are solicited using Likert scales that vary in length, with 3-6 response options per item. The SF-36 can be scored into the 8 health domains named above and two overall summary scores: physical component summary (PCS) and mental component summary (MCS) scores. The domain and summary scores range from 0 to 100; higher scores indicate better levels of function and/or better health |
| Change From Baseline to Week 12 in Borg Dyspnea Score | Baseline to 12 weeks | The Borg Dyspnea score is a self-rating scale to evaluate the severity of dyspnea (from 0 no shortness of breath at all to 10 very, very severe / maximal shortness of breath). The scale was completed at the beginning and conclusion of each 6-minute walk test at baseline and at Week 12. Median change from baseline in scoring was reported. |
| Resting Heart Rate | Baseline to 12 weeks | Change in heart rate between Week 12 and Baseline |
| Total Lean Mass | Baseline to 12 weeks | Change from baseline lean mass at week 12. |
| Insulin Resistance | Baseline to 12 weeks | Insulin resistance measured by the Homeostatic Model Assessment for Insulin Resistance insulin resistance score (HOMA-IR) utilizing the formula: fasting plasma glucose (mmol/l) times fasting serum insulin (mU/l) divided by 22.5. Low HOMA-IR values indicate high insulin sensitivity, whereas high HOMA-IR values indicate low insulin sensitivity (insulin resistance). |
| BNP | Baseline to 12 weeks | Change from baseline B-type natriuretic peptide level at week 12. |
| Change From Baseline on the SF-36 Physical Component Summary (PCS) Score | Baseline to 12 weeks | SF-36 consists of 36 questions measuring 8 health domains: physical functioning, bodily pain, role limitations due to physical problems, role limitations due to emotional problems, general health perceptions, mental health, social function, and vitality. The patient's responses are solicited using Likert scales that vary in length, with 3-6 response options per item. The SF-36 can be scored into the 8 health domains named above and two overall summary scores: physical component summary (PCS) and mental component summary (MCS) scores. The domain and summary scores range from 0 to 100; higher scores indicate better levels of function and/or better health |
| Minutes of Moderate-vigorous Activity | Baseline to 12 Weeks | Change in minutes between Week 12 and Baseline |
| Visceral Fat Volume | Baseline to Week 12 | Change in fat volume between Week 12 and Baseline |
Countries
United States
Participant flow
Pre-assignment details
After participant is enrolled, they are given a fitbit device to wear for a 14 day run-in period leading up to the baseline visit. After the baseline visit is completed they are then randomized. Reasons why a participants may have been removed from study prior to randomization include the participant dropping out for personal or medical issues.
Participants by arm
| Arm | Count |
|---|---|
| Smartphone Text Messaging Group receives personalized, health coaching via smart text messages.
Smartphone Text Messaging: A HIPPA compliant text messaging platform is linked to the Fitbit Application Program Interface. Real time activity data will be transmitted from the subject's smartphone to our mHealth platform via cellular network. Subjects will receive 3 texts/day in sync with their preferred morning, lunch, and evening leisure schedule (defined at enrollment). These texts will use personal, disease-specific, and provider information to deliver 2 types of messages customized to the current step count and sent in equal proportion. Messages are designed to facilitate self-awareness, reinforce step targets, and link physical activity with a reward or memorable cue.
Fitbit Charge HR: The Fitbit Charge HR tri-axial accelerometer will be used to continuously gather data on physical activity, heart rate, and sleep. This device provides feedback in units of activity (steps, stairs climbed, activity time, and exercise time) and heart rate (per second when active, per 5 seconds when inactive). It has been validated against research devices in free-living conditions and is relatively inexpensive. | 20 |
| No Smartphone Text Messaging Group does not receive personalized, health coaching via smart text messages.
Fitbit Charge HR: The Fitbit Charge HR tri-axial accelerometer will be used to continuously gather data on physical activity, heart rate, and sleep. This device provides feedback in units of activity (steps, stairs climbed, activity time, and exercise time) and heart rate (per second when active, per 5 seconds when inactive). It has been validated against research devices in free-living conditions and is relatively inexpensive. | 22 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Randomized Treatment | Withdrawal by Subject | 0 | 2 | 0 |
| Run-in Period (2 Weeks) | Adverse Event | 1 | 0 | 0 |
| Run-in Period (2 Weeks) | Protocol Violation | 1 | 0 | 0 |
| Run-in Period (2 Weeks) | Withdrawal by Subject | 5 | 0 | 0 |
Baseline characteristics
| Characteristic | No Smartphone Text Messaging | Total | Smartphone Text Messaging |
|---|---|---|---|
| Age, Continuous | 47 Years | 47 Years | 47 Years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 9 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 19 Participants | 32 Participants | 13 Participants |
| Sex: Female, Male Female | 21 Participants | 36 Participants | 15 Participants |
| Sex: Female, Male Male | 1 Participants | 6 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 22 |
| other Total, other adverse events | 5 / 20 | 4 / 22 |
| serious Total, serious adverse events | 2 / 20 | 0 / 22 |
Outcome results
Primary
Daily Step Count
Change from baseline mean daily step count at week 12.
Time frame: Baseline to 12 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Smartphone Text Messaging | Daily Step Count | 1409 Steps |
| No Smartphone Text Messaging | Daily Step Count | -149 Steps |
Secondary
BNP
Change from baseline B-type natriuretic peptide level at week 12.
Time frame: Baseline to 12 weeks
Population: Only 17 participants in the Smartphone Text Messaging arm were analyzed due to research shut downs during COVID. Any assessments requiring an in-person visit were not completed for one participant.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Smartphone Text Messaging | BNP | -2 pg/mL |
| No Smartphone Text Messaging | BNP | 7 pg/mL |
Secondary
Change From Baseline at Week 12 in emPHasis-10 Questionnaire Score
Quality of life was assessed using the emPHasis-10 questionnaire, a disease-specific self-administered 10-question questionnaire designed for routine assessment of health-related quality of life in pulmonary hypertension. Total score can range from 0 to 50, with higher scores indicating a worse quality of life. Change from Baseline was calculated as the value at Week 12 minus the value at Baseline. The Week 12 value was defined as the last assessment at or prior to Week 12.
Time frame: Baseline to 12 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Smartphone Text Messaging | Change From Baseline at Week 12 in emPHasis-10 Questionnaire Score | -3 units on a scale |
| No Smartphone Text Messaging | Change From Baseline at Week 12 in emPHasis-10 Questionnaire Score | 1.0 units on a scale |
Secondary
Change From Baseline on the SF-36 Mental Component Summary (MCS) Score
SF-36 consists of 36 questions measuring 8 health domains: physical functioning, bodily pain, role limitations due to physical problems, role limitations due to emotional problems, general health perceptions, mental health, social function, and vitality. The patient's responses are solicited using Likert scales that vary in length, with 3-6 response options per item. The SF-36 can be scored into the 8 health domains named above and two overall summary scores: physical component summary (PCS) and mental component summary (MCS) scores. The domain and summary scores range from 0 to 100; higher scores indicate better levels of function and/or better health
Time frame: Baseline to 12 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Smartphone Text Messaging | Change From Baseline on the SF-36 Mental Component Summary (MCS) Score | 3.8 units on a scale |
| No Smartphone Text Messaging | Change From Baseline on the SF-36 Mental Component Summary (MCS) Score | 1.5 units on a scale |
Secondary
Change From Baseline on the SF-36 Physical Component Summary (PCS) Score
SF-36 consists of 36 questions measuring 8 health domains: physical functioning, bodily pain, role limitations due to physical problems, role limitations due to emotional problems, general health perceptions, mental health, social function, and vitality. The patient's responses are solicited using Likert scales that vary in length, with 3-6 response options per item. The SF-36 can be scored into the 8 health domains named above and two overall summary scores: physical component summary (PCS) and mental component summary (MCS) scores. The domain and summary scores range from 0 to 100; higher scores indicate better levels of function and/or better health
Time frame: Baseline to 12 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Smartphone Text Messaging | Change From Baseline on the SF-36 Physical Component Summary (PCS) Score | -0.8 units on a scale |
| No Smartphone Text Messaging | Change From Baseline on the SF-36 Physical Component Summary (PCS) Score | -0.4 units on a scale |
Secondary
Change From Baseline to Week 12 in Borg Dyspnea Score
The Borg Dyspnea score is a self-rating scale to evaluate the severity of dyspnea (from 0 no shortness of breath at all to 10 very, very severe / maximal shortness of breath). The scale was completed at the beginning and conclusion of each 6-minute walk test at baseline and at Week 12. Median change from baseline in scoring was reported.
Time frame: Baseline to 12 weeks
Population: Only 17 participants in the Smartphone Text Messaging arm were analyzed due to research shut downs during COVID. Any assessments requiring an in-person visit were not completed for one participant.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Smartphone Text Messaging | Change From Baseline to Week 12 in Borg Dyspnea Score | -1.0 units on a scale |
| No Smartphone Text Messaging | Change From Baseline to Week 12 in Borg Dyspnea Score | 0.0 units on a scale |
Secondary
Daily Aerobic Time
Change in minutes of activity per day between Week 12 and Baseline
Time frame: Baseline to 12 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Smartphone Text Messaging | Daily Aerobic Time | 10 minutes |
| No Smartphone Text Messaging | Daily Aerobic Time | -16 minutes |
Secondary
Insulin Resistance
Insulin resistance measured by the Homeostatic Model Assessment for Insulin Resistance insulin resistance score (HOMA-IR) utilizing the formula: fasting plasma glucose (mmol/l) times fasting serum insulin (mU/l) divided by 22.5. Low HOMA-IR values indicate high insulin sensitivity, whereas high HOMA-IR values indicate low insulin sensitivity (insulin resistance).
Time frame: Baseline to 12 weeks
Population: Only 17 participants in the Smartphone Text Messaging arm were analyzed due to research shut downs during COVID. Any assessments requiring an in-person visit were not completed for one participant.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Smartphone Text Messaging | Insulin Resistance | 0.3 units on a scale |
| No Smartphone Text Messaging | Insulin Resistance | 0.0 units on a scale |
Secondary
Minutes of Moderate-vigorous Activity
Change in minutes between Week 12 and Baseline
Time frame: Baseline to 12 Weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Smartphone Text Messaging | Minutes of Moderate-vigorous Activity | 1.6 minutes |
| No Smartphone Text Messaging | Minutes of Moderate-vigorous Activity | -0.6 minutes |
Secondary
Percentage of Days Participants Met Their Daily Step Count Goal
All participants were provided with an Fitbit Charge Heart Rate mobile device to monitor daily step counts, activity time, and aerobic time. The daily goal was communicated via text to the intervention group and was the baseline step count average for the control group. Increased daily goal attainment indicates increased activity level
Time frame: Baseline to 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Smartphone Text Messaging | Percentage of Days Participants Met Their Daily Step Count Goal | 41 percent of days at goal across group |
| No Smartphone Text Messaging | Percentage of Days Participants Met Their Daily Step Count Goal | 24 percent of days at goal across group |
Secondary
Resting Heart Rate
Change in heart rate between Week 12 and Baseline
Time frame: Baseline to 12 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Smartphone Text Messaging | Resting Heart Rate | 0 beats per minute |
| No Smartphone Text Messaging | Resting Heart Rate | 0 beats per minute |
Secondary
Right Ventricle (RV) Strain
Change from baseline of RV free wall longitudinal strain at week 12.
Time frame: Baseline to 12 weeks
Population: Only 17 participants in the Smartphone Text Messaging arm were analyzed due to research shut downs during COVID. Any assessments requiring an in-person visit were not completed for one participant.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Smartphone Text Messaging | Right Ventricle (RV) Strain | -0.1 percentage of deformation |
| No Smartphone Text Messaging | Right Ventricle (RV) Strain | 0.4 percentage of deformation |
Secondary
Six Minute Walk Test Distance
Change from baseline of six minute walk test distance (meters) at week 12.
Time frame: Baseline to 12 weeks
Population: Only 17 participants in the Smartphone Text Messaging arm were analyzed due to research shut downs during COVID. Any assessments requiring an in-person visit were not completed for one participant.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Smartphone Text Messaging | Six Minute Walk Test Distance | 3 meters |
| No Smartphone Text Messaging | Six Minute Walk Test Distance | -6 meters |
Secondary
Total Lean Mass
Change from baseline lean mass at week 12.
Time frame: Baseline to 12 weeks
Population: Only 17 participants in the Smartphone Text Messaging arm were analyzed due to research shut downs during COVID. Any assessments requiring an in-person visit were not completed for one participant.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Smartphone Text Messaging | Total Lean Mass | 0.1 kilograms |
| No Smartphone Text Messaging | Total Lean Mass | 0.0 kilograms |
Secondary
Visceral Fat Volume
Change in fat volume between Week 12 and Baseline
Time frame: Baseline to Week 12
Population: Only 17 participants in the Smartphone Text Messaging arm were analyzed due to research shut downs during COVID. Any assessments requiring an in-person visit were not completed for one participant.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Smartphone Text Messaging | Visceral Fat Volume | -67 mL |
| No Smartphone Text Messaging | Visceral Fat Volume | 21 mL |