HRV as a Marker of Treatment Response in PAH Arterial Hypertension

• ClinicalTrials.gov Identifier: NCT04451850
• Recruitment Status: Recruiting
• First Posted: June 30, 2020
• Last Update Posted: July 1, 2021
• Sponsor: University of Cincinnati
• Information provided by (Responsible Party): Arun Jose, University of Cincinnati

Study Description

Brief Summary:

This is a prospective longitudinal cohort study to determine the value of HRV obtained using noninvasive actigraphy to quantify the response to pulmonary vasodilator therapy in newly diagnosed PAH patients

Condition or disease	Intervention/treatment
Pulmonary Arterial Hypertension	Other: Noninvasive actigraphy monitor

Detailed Description:

This single center prospective longitudinal cohort study will take place at the University of Cincinnati (UC). We will screen adult patients newly diagnosed with PAH and placed on targeted pulmonary vasodilator therapy by their treating physician for enrollment.

We will enroll 35 eligible participants over a two-year period. HRV will be measured using the Polar™ H10 wearable chest actigraphy device in conjunction with analytic software to capture HRV data.

After enrollment and completion of the baseline visit, study participants will receive chest actigraphy device to measure their heart rate for a two hour period twice a week during study participation. Follow up research visits will be conducted at one-month, 3-months, and 6-months to sync the actigraphy device and assess any AE's.

In-between these visits, study staff will communicate with participants at two weeks, two months, 4 months, and 5 months, to identify and address any issues with study actigraphic device, assess any adverse events and maintain regular contact with study participants.

Throughout study participation, subjects will continue routine clinical care at the direction of their treating physician as needed.

Study Design

• Study Type: Observational
• Estimated Enrollment: 35 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Heart Rate Variability (HRV) as a Marker of Treatment Response in Pulmonary Arterial Hypertension (PAH)
• Actual Study Start Date: June 1, 2021
• Estimated Primary Completion Date: June 30, 2023
• Estimated Study Completion Date: June 30, 2023

Groups and Cohorts

Intervention Details:

• Other: Noninvasive actigraphy monitor
  Noninvasive chest-mounted actigraphic device to be worn for 2 hour intervals two times per week during the six month study participation.
  Other Name: Polar H10 Heart Rate Monitor

Outcome Measures

Primary Outcome Measures :

1. Change from baseline in HRV via RMSSD [ Time Frame: 6 months ]
   Change from baseline in Root Mean Squared Successive Differences (RMSSD) measure of Heart Rate variability in patients on targeted therapy

Secondary Outcome Measures :

1. Change from baseline in HRV via SDNN [ Time Frame: 6 months ]
   Change from baseline in Standard Deviation of N-to-N (SDNN) measure of Heart Rate Variability in patients on targeted therapy
2. Correlation with Cardiac Magnetic Resonance Imaging Variables [ Time Frame: 6 months ]
   Correlation between RMSSD and SDNN with key cardiac Magnetic Resonance Imaging Variables of PAH disease, the Right Ventricular Stroke Volume
3. Correlation with NTproBNP [ Time Frame: 6 months ]
   Correlation between RMSSD and SDNN with N-terminal Pro-B-Type Natriuretic Peptide (NTproBNP), a marker of PAH disease severity and treatment response
4. Correlation with REVEAL 2.0 Risk Score [ Time Frame: 6 months ]
   Correlation between RMSSD and SDNN with the REVEAL 2.0 Risk score, a measure of PAH prognosis
5. Correlation with CAMPHOR Quality of Life Score [ Time Frame: 6 months ]
   Correlation between RMSSD and SDNN with the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) score, a 3-domain quality of life assessment tool specific to PAH patients

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Patients seen at the University of Cincinnati PAH Clinic in Cincinnati, Ohio

Criteria

Inclusion Criteria:

• All adult patients (ages 18-70) of any functional class with a new diagnosis of PAH (World health Organization Group 1) placed on targeted therapy
• Eligible PAH etiologies include idiopathic PAH, associated with connective tissue disease, human immunodeficiency virus, hereditary, or portopulmonary hypertension
• Right heart catheterization (RHC) hemodynamics with a mean pulmonary arterial pressure >=20 millimetres of mercury at rest, a pulmonary capillary wedge pressure <= 15 millimetres of mercury, and a pulmonary vascular resistance >= 3 woods units

Exclusion Criteria:

• Inability to undergo (non-contrast) Magnetic Resonance Imaging (MRI) testing
• On chronotropic agents (Beta-Blockers, anti-arrhythmic medications, etc.) that could affect the calculation and interpretation of HRV measures
• Conditions that could affect the accuracy of MRI imaging, including a history previously repaired or unrepaired congenital heart defects, ventricular or atrial septal defects, or other anatomic cardiac abnormalities)
• Inability to complete a six-minute walk test
• Currently being on targeted PAH therapy at the time of consent and enrollment
• Thyroid disease, known arrhythmias in the past six months, uncontrolled anemia with a hemoglobin less than 7 grams per deciliter, untreated coronary artery disease or a diagnosis of myocardial infarction in the past 6 months, the presence of a cardiac pacemaker
• Clinically significant lung disease (including pulmonary function testing forced vital capacity < 60%), a positive ventilation/perfusion scan, uncontrolled sleep apnea not adherent with noninvasive positive pressure ventilation
• Unable to consent, pregnant women, and prisoners.

Contacts and Locations

Contacts

Contact: Susan McMahan, BSN, RN, CCRP; 513-558-4376; susan.mcmahan@uc.edu

Locations

United States, Ohio

University of Cincinnati; Recruiting

Cincinnati, Ohio, United States, 45267

Contact: Arun Jose, MD, MS 513-558-7451 josean@ucmail.uc.edu

Contact: Susan Sellers, BSN, CCRP 513-558-4376 susan.mcmahan@uc.edu

Sponsors and Collaborators

University of Cincinnati

Investigators

• Principal Investigator: Arun Jose, MD, MS; University of Cincinnati

More Information

Publications:

Heresi GA, Dweik RA. Strengths and limitations of the six-minute-walk test: a model biomarker study in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011 May 1;183(9):1122-4. doi: 10.1164/rccm.201012-2079ED.

Ulrich S, Fischler M, Speich R, Bloch KE. Wrist actigraphy predicts outcome in patients with pulmonary hypertension. Respiration. 2013;86(1):45-51. doi: 10.1159/000342351. Epub 2012 Dec 11.

Pugh ME, Buchowski MS, Robbins IM, Newman JH, Hemnes AR. Physical activity limitation as measured by accelerometry in pulmonary arterial hypertension. Chest. 2012 Dec;142(6):1391-1398. doi: 10.1378/chest.12-0150.

• Responsible Party: Arun Jose, Assistant Professor of Medicine, University of Cincinnati
• ClinicalTrials.gov Identifier: NCT04451850
• Other Study ID Numbers: 2019-1371
• First Posted: June 30, 2020
• Last Update Posted: July 1, 2021
• Last Verified: June 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Additional relevant MeSH terms:

Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension; Vascular Diseases; Cardiovascular Diseases; Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases