Trial Outcomes & Findings for Interventions Against Insulin Resistance in Pulmonary Arterial Hypertension (NCT NCT03617458)

NCT ID: NCT03617458

Last Updated: 2025-09-22

Results Overview

The change in meters walked for the six-minute walk distance from baseline to week 12

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 73 participants
• Primary outcome timeframe: baseline and 12 weeks
• Results posted on: 2025-09-22

Participant Flow

Recruitment occured between 8/23/2018-8/22/2023. Recruitment occurred in clinics at each of the participating sites.

There was a participant run-in for the fitbit portion of the study. Run-in was a 2-week period.

Participant milestones

Measure	Metformin + mHealth Intervention Patients will receive active ingredient medicine with mHealth texting platform, which are messages designed to facilitate self-awareness, reinforce step targets, and link physical activity with a reward or memorable cue. Subjects will receive metformin 500mg. Patients will titrate the medication as follows: 500mg po daily x 5 days, 500mg po twice a day (BID) x 5 days, 500mg by mouth (po) three times a day (TID) x 5 days,1000mg po BID x 69 days (12 weeks total). Metformin: Metformin is a drug has been on the market for several decades and is considered first line therapy for diabetes mellitus type 2. mHealth Intervention: Our Health Insurance Portability and Accountability Act (HIPAA) compliant texting 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 assigned to the texting arm will receive 3 texts/day in sync with their preferred morning, lunch, and evening leisure schedule, which is 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.	Placebo + Usual Care Patient will receive non active medicine and routine medical care. Placebo: A treatment with no active ingredients or therapeutic effect. Usual Care: Our HIPAA data will be transmitted from the subject's smartphone to our mHealth platform via cellular network.	Metformin + Usual Care Patient will receive active ingredient medicine with routine medical care. Subjects will receive metformin 500mg. Patients will titrate the medication as follows: 500mg po daily x 5 days, 500mg po BID x 5 days, 500mg po TID x 5 days,1000mg po BID x 69 days (12 weeks total). Metformin: Metformin is a drug has been on the market for several decades and is considered first line therapy for diabetes mellitus type 2. Usual Care: Our HIPAA data will be transmitted from the subject's smartphone to our mHealth platform via cellular network.	Placebo + mHealth Intervention Patient will receive non active medicine and the mHealth texting platform, which are messages designed to facilitate self-awareness, reinforce step targets, and link physical activity with a reward or memorable cue. Placebo: A treatment with no active ingredients or therapeutic effect. mHealth Intervention: Our Health Insurance Portability and Accountability Act (HIPAA) compliant texting 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 assigned to the texting arm will receive 3 texts/day in sync with their preferred morning, lunch, and evening leisure schedule, which is 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.
Overall Study STARTED	18	17	19	19
Overall Study COMPLETED	15	14	18	19
Overall Study NOT COMPLETED	3	3	1	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Interventions Against Insulin Resistance in Pulmonary Arterial Hypertension

Baseline characteristics by cohort

Measure	Metformin + mHealth Intervention n=18 Participants Patients will receive active ingredient medicine with mHealth texting platform, which are messages designed to facilitate self-awareness, reinforce step targets, and link physical activity with a reward or memorable cue. Subjects will receive metformin 500mg. Patients will titrate the medication as follows: 500mg po daily x 5 days, 500mg po twice a day (BID) x 5 days, 500mg by mouth (po) three times a day (TID) x 5 days,1000mg po BID x 69 days (12 weeks total). Metformin: Metformin is a drug has been on the market for several decades and is considered first line therapy for diabetes mellitus type 2. mHealth Intervention: Our Health Insurance Portability and Accountability Act (HIPAA) compliant texting 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 assigned to the texting arm will receive 3 texts/day in sync with their preferred morning, lunch, and evening leisure schedule, which is 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.	Placebo + Usual Care n=17 Participants Patient will receive non active medicine and routine medical care. Placebo: A treatment with no active ingredients or therapeutic effect. Usual Care: Our HIPAA data will be transmitted from the subject's smartphone to our mHealth platform via cellular network.	Metformin + Usual Care n=19 Participants Patient will receive active ingredient medicine with routine medical care. Subjects will receive metformin 500mg. Patients will titrate the medication as follows: 500mg po daily x 5 days, 500mg po BID x 5 days, 500mg po TID x 5 days,1000mg po BID x 69 days (12 weeks total). Metformin: Metformin is a drug has been on the market for several decades and is considered first line therapy for diabetes mellitus type 2. Usual Care: Our HIPAA data will be transmitted from the subject's smartphone to our mHealth platform via cellular network.	Placebo + mHealth Intervention n=19 Participants Patient will receive non active medicine and the mHealth texting platform, which are messages designed to facilitate self-awareness, reinforce step targets, and link physical activity with a reward or memorable cue. Placebo: A treatment with no active ingredients or therapeutic effect. mHealth Intervention: Our Health Insurance Portability and Accountability Act (HIPAA) compliant texting 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 assigned to the texting arm will receive 3 texts/day in sync with their preferred morning, lunch, and evening leisure schedule, which is 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.	Total n=73 Participants Total of all reporting groups
Age, Continuous	47.4 years STANDARD_DEVIATION 17.4 • n=5 Participants	46.6 years STANDARD_DEVIATION 10.7 • n=7 Participants	48.8 years STANDARD_DEVIATION 13.7 • n=5 Participants	47 years STANDARD_DEVIATION 12.2 • n=4 Participants	47.5 years STANDARD_DEVIATION 13.5 • n=21 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	10 Participants n=7 Participants	15 Participants n=5 Participants	16 Participants n=4 Participants	53 Participants n=21 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	7 Participants n=7 Participants	4 Participants n=5 Participants	3 Participants n=4 Participants	20 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	18 Participants n=5 Participants	16 Participants n=7 Participants	18 Participants n=5 Participants	19 Participants n=4 Participants	71 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	6 Participants n=21 Participants
Race (NIH/OMB) White	14 Participants n=5 Participants	15 Participants n=7 Participants	15 Participants n=5 Participants	19 Participants n=4 Participants	63 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Region of Enrollment United States	18 participants n=5 Participants	17 participants n=7 Participants	19 participants n=5 Participants	19 participants n=4 Participants	73 participants n=21 Participants

PRIMARY outcome

Timeframe: baseline and 12 weeks

The change in meters walked for the six-minute walk distance from baseline to week 12

Outcome measures

Measure	Metformin + mHealth Intervention n=14 Participants Patients will receive active ingredient medicine with mHealth texting platform, which are messages designed to facilitate self-awareness, reinforce step targets, and link physical activity with a reward or memorable cue. Subjects will receive metformin 500mg. Patients will titrate the medication as follows: 500mg po daily x 5 days, 500mg po twice a day (BID) x 5 days, 500mg by mouth (po) three times a day (TID) x 5 days,1000mg po BID x 69 days (12 weeks total). Metformin: Metformin is a drug has been on the market for several decades and is considered first line therapy for diabetes mellitus type 2. mHealth Intervention: Our Health Insurance Portability and Accountability Act (HIPAA) compliant texting 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 assigned to the texting arm will receive 3 texts/day in sync with their preferred morning, lunch, and evening leisure schedule, which is 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.	Placebo + Usual Care n=12 Participants Patient will receive non active medicine and routine medical care. Placebo: A treatment with no active ingredients or therapeutic effect. Usual Care: Our HIPAA data will be transmitted from the subject's smartphone to our mHealth platform via cellular network.	Metformin + Usual Care n=16 Participants Patient will receive active ingredient medicine with routine medical care. Subjects will receive metformin 500mg. Patients will titrate the medication as follows: 500mg po daily x 5 days, 500mg po BID x 5 days, 500mg po TID x 5 days,1000mg po BID x 69 days (12 weeks total). Metformin: Metformin is a drug has been on the market for several decades and is considered first line therapy for diabetes mellitus type 2. Usual Care: Our HIPAA data will be transmitted from the subject's smartphone to our mHealth platform via cellular network.	Placebo + mHealth Intervention n=18 Participants Patient will receive non active medicine and the mHealth texting platform, which are messages designed to facilitate self-awareness, reinforce step targets, and link physical activity with a reward or memorable cue. Placebo: A treatment with no active ingredients or therapeutic effect. mHealth Intervention: Our Health Insurance Portability and Accountability Act (HIPAA) compliant texting 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 assigned to the texting arm will receive 3 texts/day in sync with their preferred morning, lunch, and evening leisure schedule, which is 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.
Change From Baseline in Six Minute Walk Distance (Meters) Baseline	414.5 meters Standard Deviation 87.9	461.7 meters Standard Deviation 135.6	448.9 meters Standard Deviation 85.9	483.0 meters Standard Deviation 85.6
Change From Baseline in Six Minute Walk Distance (Meters) 12-Week	457.2 meters Standard Deviation 110.2	474.9 meters Standard Deviation 123.6	454.8 meters Standard Deviation 112.3	485.6 meters Standard Deviation 72.3

PRIMARY outcome

Timeframe: baseline and 12 weeks

Change from baseline in WHO functional class at week 12. The World Health Organization (WHO) functional class system was created to define the severity of an individual's symptoms and how they impact on day-to-day activities. The columns represent the randomization assignment and the rows represent if a change in WHO functional class occurred by the participant from baseline to week 12.

Outcome measures

Measure	Metformin + mHealth Intervention n=16 Participants Patients will receive active ingredient medicine with mHealth texting platform, which are messages designed to facilitate self-awareness, reinforce step targets, and link physical activity with a reward or memorable cue. Subjects will receive metformin 500mg. Patients will titrate the medication as follows: 500mg po daily x 5 days, 500mg po twice a day (BID) x 5 days, 500mg by mouth (po) three times a day (TID) x 5 days,1000mg po BID x 69 days (12 weeks total). Metformin: Metformin is a drug has been on the market for several decades and is considered first line therapy for diabetes mellitus type 2. mHealth Intervention: Our Health Insurance Portability and Accountability Act (HIPAA) compliant texting 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 assigned to the texting arm will receive 3 texts/day in sync with their preferred morning, lunch, and evening leisure schedule, which is 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.	Placebo + Usual Care n=14 Participants Patient will receive non active medicine and routine medical care. Placebo: A treatment with no active ingredients or therapeutic effect. Usual Care: Our HIPAA data will be transmitted from the subject's smartphone to our mHealth platform via cellular network.	Metformin + Usual Care n=17 Participants Patient will receive active ingredient medicine with routine medical care. Subjects will receive metformin 500mg. Patients will titrate the medication as follows: 500mg po daily x 5 days, 500mg po BID x 5 days, 500mg po TID x 5 days,1000mg po BID x 69 days (12 weeks total). Metformin: Metformin is a drug has been on the market for several decades and is considered first line therapy for diabetes mellitus type 2. Usual Care: Our HIPAA data will be transmitted from the subject's smartphone to our mHealth platform via cellular network.	Placebo + mHealth Intervention n=18 Participants Patient will receive non active medicine and the mHealth texting platform, which are messages designed to facilitate self-awareness, reinforce step targets, and link physical activity with a reward or memorable cue. Placebo: A treatment with no active ingredients or therapeutic effect. mHealth Intervention: Our Health Insurance Portability and Accountability Act (HIPAA) compliant texting 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 assigned to the texting arm will receive 3 texts/day in sync with their preferred morning, lunch, and evening leisure schedule, which is 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.
Change From Baseline to Week 12 in World Health Organization Functional Class (WHO FC) Did not improve Functional Class	15 Participants	12 Participants	14 Participants	13 Participants
Change From Baseline to Week 12 in World Health Organization Functional Class (WHO FC) Improved Functional Class by at least 1	1 Participants	2 Participants	3 Participants	5 Participants

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

Change in body weight as measured by assessing weight in kilograms at baseline and at week 12.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

Change from baseline BMI at week 12. BMI is defined as a measure of body fat based on height and weight that applies to adult men and women.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

Change from baseline six-minute walk test distance (meters) at week 12.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

Change from baseline Borg dyspnea score at week 12.

The Borg dyspnea score is a measure of the physical activity intensity level based on the subject's perceived exertion. Subjects will rate at resting and peak exercise. Targets exercise capacity.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

Change from baseline Emphasis-10 quality of life survey score at week 12. Survey completed at baseline and 12 weeks.

The emPHasis-10 is a short and easy questionnaire that consists of 10 items which address breathlessness, fatigue, control and confidence. Each item is scored on a semantic differential six-point scale (0-5), with contrasting adjectives at each end. A total emPHasis-10 score is derived using simple aggregation of the 10 items. emPHasis-10 scores range from 0 to 50, higher scores indicate worse quality of life.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

Change from the baseline mean daily step count at week 12. Data obtained by the mHealth device.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

Assess the frequency (% of days) that the daily step target was achieved over time. Data obtained by the mHealth device.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

Change from baseline daily aerobic time at week 12. Aerobic time is defined as total time in minutes spent walking continuously for > 10 minutes without breaking for > 1 minute.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

This variable will be assessed by FitBit and is expressed in step counts per minute. Mean value from the last week in the study will be evaluated and mean change from baseline will be calculated.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

Monitored regularly using activity tracking device (per second when active, per 5 seconds when inactive). Subject's resting and peak exercise heart rate will also be recorded at baseline and week 12. Targets exercise capacity. Heart rate is expressed as beats per minute.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

Change from baseline insulin resistance at week 12. Insulin resistance will be quantified using the homeostatic model assessment of insulin resistance (HOMA-IR), which estimates insulin resistance through fasting plasma insulin and glucose ratios. Targets mechanism of improved exercise capacity.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

As measured by plasma estradiol in pg/ml, DHEA in mcg/ml, total testosterone in ng/dl, bioavailable testosterone in ng/dl, progesterone in ng/ml, and sex hormone binding globulin (SHBG) in nmol/L at baseline and week 12. These laboratory values will be aggregated to assess the number of participants with abnormal laboratory values.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

As measured by the laboratory values Estrone (E1), Estradiol (E2), 2-OHE1, 2-OHE2, 2-MeOE1, 2-MeOE2, 4-OHE1, 4-MeOE1, 4-MeOE2, 16a-OHE1, 17-epiE3, Estriol (E3), 16-ketoE2, 16-epiE3 with pM per mg of urine creatinine. These laboratory values will be assessed at baseline and week 12 and then aggregated to assess the number of participants with abnormal laboratory values.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

As measured by total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and non - high-density lipoprotein cholesterol with mg/dl as the units of measure at baseline and week 12. These laboratory values will be aggregated to assess number of participants with abnormal laboratory values.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

As measured by plasma free fatty acid profiles at baseline and week 12. Free fatty acids will be measured in mmol/L. This laboratory value will be assessed by the number of patients with abnormal laboratory values.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

As measured by plasma acylcarnitine profiles at baseline and week 12. We will be measuring the laboratory values of C2, C3, C3-dicarboxylic, C4, C4- hydroxyl, C4-dicarboxylic, C5, C5:1, C5 - hydroxy, C5-dicarboxylic, C6, C8, C10, C10:1, C10:2, C12, C14, C14:1, C14:2, C14-hydroxy, C16, C16:1, C161:-hydroxy, C16-hydroxy, C18, C18:1, C18:2, C18-hydroxy, C18:1-hydroxy, C18:2-hydroxy in the unit of measure nmol/L. These laboratory values will be aggregated to assess the number of participants with abnormal laboratory values.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

Change from baseline B-type natriuretic peptide (BNP) level at week 12. BNP is a marker of myocardial stress which decreases with exercise training and measured in pg/ml. Targets mechanism of improved exercise capacity.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

Change from baseline quadriceps Skeletal Muscle Triglyceride Content at week 12 as measured by % triglycerides.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

Change from baseline quadriceps Skeletal Muscle Fatigue at week 12 as measured by total time to muscle fatigue during the muscle strength and function test.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

Change from baseline quadriceps Skeletal Muscle Strength during the Muscle Strength and Function Test at week 12 as measured by maximum contraction strength.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

Change from baseline in quadriceps skeletal muscle contractile tissue cross-sectional at week 12 as measured by the relative change in the maximum cross-sectional area of muscle tissue of the quadriceps muscle group, measured in the axial anatomical plane.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

Change from baseline in right ventricle Myocardial Muscle Triglyceride Content results at week 12 as measured by % triglycerides.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

Change from baseline in Tricuspid Annular Plane systolic Excursion (TAPSE) expressed in mm on echocardiogram results at week 12.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

Change from baseline in RV and Left Ventricle (LV) Ejection Fraction values on echocardiogram results at week 12 and expressed in percentage (%).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

Change from baseline in right ventricle Fractional Area on echocardiogram results at week 12 and expressed in percentage (%).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

Change from baseline in Tricuspid Annular Velocity (S') on echocardiogram results at week 12 and expressed in cm/sec.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

Change from baseline in Tricuspid Regurgitant (TR) Velocity on echocardiogram results at week 12 and expressed in m/sec.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

Change from baseline in the estimated right ventricle and right atrial pressure on echocardiogram results at week 12 and expressed in mmHg.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

Change from baseline in right and left ventricular diastolic function as assessed by Doppler inflow patterns on echocardiogram results at week 12

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

Change from baseline in right ventricle free wall longitudinal strain on echocardiogram results at week 12 and expressed as percent (%) change in myocardial deformation.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

To compare and define the screening clinical characteristics of responders and non-responders to mHealth intervention or no intervention and/or metformin at week 12. We will be taking into account all patient screening data including demographic information, medical history, current medication regimen, physical exam, 6MWT, echocardiogram, MRS, skeletal muscle function test, emphasis-10 survey, WHO functional class, and laboratory values. These results will be aggregated and the results compared to the same characteristics at the end of week 12.

We will be assessing the number of participants with a change in screening clinical characteristics.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

Number of treatment-related adverse events as assessed by telephone calls at baseline, week one, week three, week nine, week twelve, and week seventeen.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

We will be assessing patient satisfaction of treatment interventions by looking at the number of participants with an increase or decrease in overall score on the emphasis-10 questionnaire from screening and at the end of 12 weeks.

The emPHasis-10 is a short and easy questionnaire that consists of 10 items which address breathlessness, fatigue, control and confidence. Each item is scored on a semantic differential six-point scale (0-5), with contrasting adjectives at each end. A total emPHasis-10 score is derived using simple aggregation of the 10 items. EmPHasis-10 scores range from 0 to 50, higher scores indicate worse quality of life.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

To assess the effect of a mHealth intervention or no intervention and/or metformin or placebo on dropout rates over 12 weeks.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

To assess the effect of a mHealth intervention or no intervention and/or metformin or placebo on PAH-related hospitalization incidences over 12 weeks. Number of patients will be assessed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and end of 12 weeks

Change from baseline in patient medication regimen at week 12 as measured by percentage (%) of subjects with a change in medication regimen.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline to/and 12 weeks

To assess the effect of a mHealth intervention or no intervention and/or metformin or placebo on incidence of death over 12 weeks.

Outcome measures

Outcome data not reported

Adverse Events

Metformin + mHealth Intervention

Serious events: 5 serious events

Other events: 9 other events

Deaths: 0 deaths

Placebo + Usual Care

Serious events: 3 serious events

Other events: 7 other events

Deaths: 0 deaths

Metformin + Usual Care

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

Placebo + mHealth Intervention

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Measure	Metformin + mHealth Intervention n=18 participants at risk Patients will receive active ingredient medicine with mHealth texting platform, which are messages designed to facilitate self-awareness, reinforce step targets, and link physical activity with a reward or memorable cue. Subjects will receive metformin 500mg. Patients will titrate the medication as follows: 500mg po daily x 5 days, 500mg po twice a day (BID) x 5 days, 500mg by mouth (po) three times a day (TID) x 5 days,1000mg po BID x 69 days (12 weeks total). Metformin: Metformin is a drug has been on the market for several decades and is considered first line therapy for diabetes mellitus type 2. mHealth Intervention: Our Health Insurance Portability and Accountability Act (HIPAA) compliant texting 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 assigned to the texting arm will receive 3 texts/day in sync with their preferred morning, lunch, and evening leisure schedule, which is 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.	Placebo + Usual Care n=17 participants at risk Patient will receive non active medicine and routine medical care. Placebo: A treatment with no active ingredients or therapeutic effect. Usual Care: Our HIPAA data will be transmitted from the subject's smartphone to our mHealth platform via cellular network.	Metformin + Usual Care n=19 participants at risk Patient will receive active ingredient medicine with routine medical care. Subjects will receive metformin 500mg. Patients will titrate the medication as follows: 500mg po daily x 5 days, 500mg po BID x 5 days, 500mg po TID x 5 days,1000mg po BID x 69 days (12 weeks total). Metformin: Metformin is a drug has been on the market for several decades and is considered first line therapy for diabetes mellitus type 2. Usual Care: Our HIPAA data will be transmitted from the subject's smartphone to our mHealth platform via cellular network.	Placebo + mHealth Intervention n=19 participants at risk Patient will receive non active medicine and the mHealth texting platform, which are messages designed to facilitate self-awareness, reinforce step targets, and link physical activity with a reward or memorable cue. Placebo: A treatment with no active ingredients or therapeutic effect. mHealth Intervention: Our Health Insurance Portability and Accountability Act (HIPAA) compliant texting 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 assigned to the texting arm will receive 3 texts/day in sync with their preferred morning, lunch, and evening leisure schedule, which is 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.
Product Issues Intravenous Medication Line Malfunction/Infection	22.2% 4/18 • Number of events 5 • Adverse events were collected over study duration-baseline to 12-weeks.	0.00% 0/17 • Adverse events were collected over study duration-baseline to 12-weeks.	0.00% 0/19 • Adverse events were collected over study duration-baseline to 12-weeks.	0.00% 0/19 • Adverse events were collected over study duration-baseline to 12-weeks.
Gastrointestinal disorders Biliary Colic	0.00% 0/18 • Adverse events were collected over study duration-baseline to 12-weeks.	5.9% 1/17 • Number of events 1 • Adverse events were collected over study duration-baseline to 12-weeks.	0.00% 0/19 • Adverse events were collected over study duration-baseline to 12-weeks.	0.00% 0/19 • Adverse events were collected over study duration-baseline to 12-weeks.
Cardiac disorders Supraventriculartachycardia	0.00% 0/18 • Adverse events were collected over study duration-baseline to 12-weeks.	0.00% 0/17 • Adverse events were collected over study duration-baseline to 12-weeks.	0.00% 0/19 • Adverse events were collected over study duration-baseline to 12-weeks.	5.3% 1/19 • Number of events 2 • Adverse events were collected over study duration-baseline to 12-weeks.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	0.00% 0/18 • Adverse events were collected over study duration-baseline to 12-weeks.	5.9% 1/17 • Number of events 1 • Adverse events were collected over study duration-baseline to 12-weeks.	0.00% 0/19 • Adverse events were collected over study duration-baseline to 12-weeks.	0.00% 0/19 • Adverse events were collected over study duration-baseline to 12-weeks.
Infections and infestations Infections requiring Hospitalization	0.00% 0/18 • Adverse events were collected over study duration-baseline to 12-weeks.	5.9% 1/17 • Number of events 1 • Adverse events were collected over study duration-baseline to 12-weeks.	5.3% 1/19 • Number of events 1 • Adverse events were collected over study duration-baseline to 12-weeks.	0.00% 0/19 • Adverse events were collected over study duration-baseline to 12-weeks.
Gastrointestinal disorders Gastrointestinal Bleed	0.00% 0/18 • Adverse events were collected over study duration-baseline to 12-weeks.	5.9% 1/17 • Number of events 1 • Adverse events were collected over study duration-baseline to 12-weeks.	0.00% 0/19 • Adverse events were collected over study duration-baseline to 12-weeks.	0.00% 0/19 • Adverse events were collected over study duration-baseline to 12-weeks.
General disorders Clinical Worsening	5.6% 1/18 • Number of events 1 • Adverse events were collected over study duration-baseline to 12-weeks.	0.00% 0/17 • Adverse events were collected over study duration-baseline to 12-weeks.	0.00% 0/19 • Adverse events were collected over study duration-baseline to 12-weeks.	0.00% 0/19 • Adverse events were collected over study duration-baseline to 12-weeks.

Other adverse events

Measure	Metformin + mHealth Intervention n=18 participants at risk Patients will receive active ingredient medicine with mHealth texting platform, which are messages designed to facilitate self-awareness, reinforce step targets, and link physical activity with a reward or memorable cue. Subjects will receive metformin 500mg. Patients will titrate the medication as follows: 500mg po daily x 5 days, 500mg po twice a day (BID) x 5 days, 500mg by mouth (po) three times a day (TID) x 5 days,1000mg po BID x 69 days (12 weeks total). Metformin: Metformin is a drug has been on the market for several decades and is considered first line therapy for diabetes mellitus type 2. mHealth Intervention: Our Health Insurance Portability and Accountability Act (HIPAA) compliant texting 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 assigned to the texting arm will receive 3 texts/day in sync with their preferred morning, lunch, and evening leisure schedule, which is 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.	Placebo + Usual Care n=17 participants at risk Patient will receive non active medicine and routine medical care. Placebo: A treatment with no active ingredients or therapeutic effect. Usual Care: Our HIPAA data will be transmitted from the subject's smartphone to our mHealth platform via cellular network.	Metformin + Usual Care n=19 participants at risk Patient will receive active ingredient medicine with routine medical care. Subjects will receive metformin 500mg. Patients will titrate the medication as follows: 500mg po daily x 5 days, 500mg po BID x 5 days, 500mg po TID x 5 days,1000mg po BID x 69 days (12 weeks total). Metformin: Metformin is a drug has been on the market for several decades and is considered first line therapy for diabetes mellitus type 2. Usual Care: Our HIPAA data will be transmitted from the subject's smartphone to our mHealth platform via cellular network.	Placebo + mHealth Intervention n=19 participants at risk Patient will receive non active medicine and the mHealth texting platform, which are messages designed to facilitate self-awareness, reinforce step targets, and link physical activity with a reward or memorable cue. Placebo: A treatment with no active ingredients or therapeutic effect. mHealth Intervention: Our Health Insurance Portability and Accountability Act (HIPAA) compliant texting 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 assigned to the texting arm will receive 3 texts/day in sync with their preferred morning, lunch, and evening leisure schedule, which is 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.
Gastrointestinal disorders Gastrointestinal Issues	44.4% 8/18 • Number of events 12 • Adverse events were collected over study duration-baseline to 12-weeks.	17.6% 3/17 • Number of events 6 • Adverse events were collected over study duration-baseline to 12-weeks.	52.6% 10/19 • Number of events 14 • Adverse events were collected over study duration-baseline to 12-weeks.	15.8% 3/19 • Number of events 3 • Adverse events were collected over study duration-baseline to 12-weeks.
Product Issues Intravenous Medication Line Malfunction/Infection	0.00% 0/18 • Adverse events were collected over study duration-baseline to 12-weeks.	11.8% 2/17 • Number of events 2 • Adverse events were collected over study duration-baseline to 12-weeks.	5.3% 1/19 • Number of events 1 • Adverse events were collected over study duration-baseline to 12-weeks.	5.3% 1/19 • Number of events 1 • Adverse events were collected over study duration-baseline to 12-weeks.
Respiratory, thoracic and mediastinal disorders Common Pulmonary Hypertension Symptoms	0.00% 0/18 • Adverse events were collected over study duration-baseline to 12-weeks.	5.9% 1/17 • Number of events 1 • Adverse events were collected over study duration-baseline to 12-weeks.	10.5% 2/19 • Number of events 3 • Adverse events were collected over study duration-baseline to 12-weeks.	26.3% 5/19 • Number of events 9 • Adverse events were collected over study duration-baseline to 12-weeks.
General disorders General Infection	5.6% 1/18 • Number of events 1 • Adverse events were collected over study duration-baseline to 12-weeks.	5.9% 1/17 • Number of events 1 • Adverse events were collected over study duration-baseline to 12-weeks.	5.3% 1/19 • Number of events 1 • Adverse events were collected over study duration-baseline to 12-weeks.	5.3% 1/19 • Number of events 1 • Adverse events were collected over study duration-baseline to 12-weeks.

Additional Information

Research Programs Manager

Vanderbilt University Medical Center

Phone: 615-322-4703

Email: ph_research@vumc.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place