Feasibility of Slow-paced Respiration Therapy for Treatment of a Symptom Cluster in Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a chronic illness characterized by increased pulmonary pressures resulting in right heart failure and premature death. Common symptoms that impair quality of life and functioning are dyspnea, fatigue and sleep disturbance. This trio of symptoms is highly prevalent and forms a symptom cluster (2 or more symptoms that co-occur) in PAH. From a biological, proinflammatory cytokines are implicated in dyspnea, fatigue and sleep disturbance; there is activation of the sympathetic nervous system (SNS) and an inherent inflammatory process in PAH that contributes to the pathophysiology, but the link to this symptom cluster has not been investigated. One novel, treatment for symptom clusters is slow-paced respiration therapy using the FDA-approved device, RESPeRATE. The device contains headphones and a sensor that attaches to the chest to detect inhalation and exhalation. Musical tones synchronize with the respiratory cycle to slowly guide the user to decrease respirations. RESPeRATE moderates effects of the SNS; lowers blood pressure; improves functional capacity and ejection fraction; and significantly decreases pulmonary pressures in left heart failure. The investigators will enroll 10 women with PAH to use the RESPeRATE device to perform slow-paced respiration for 15 minutes per day for 8 weeks to determine the feasibility and effects on the SNS and inflammatory activity and the symptom cluster. The investigator's overall hypothesis is that, as compared to baseline, after eight weeks of therapy women with PAH who receive slow-based respiration therapy will have lower SNS activity and inflammatory levels, and improved dyspnea, fatigue and sleep disturbance.

Study Overview

• Status: Completed
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Other: Slow-paced respiration therapy

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Previous documentation of mean pulmonary artery pressure > 25 mm Hg with a pulmonary capillary wedge pressure (or left ventricular end-diastolic pressure) < 16 mm Hg and PVR > 3 WU at any time before study entry.
• Women with WHO Group I PAH (idiopathic, heritable, or associated with connective tissue disease, congenital heart disease, anorexigens or HIV)
• Targeted PAH therapy at stable dose for 3 months
• Age >21 years
• Ability to perform six minute walk testing without limitations in musculoskeletal function or coordination.
• Informed consent

Exclusion Criteria:

• Age < 21
• Hypotension (blood pressure < 90/60 mmHg)
• Pregnancy
• Chronic Fatigue Syndrome (current or history of)
• Known sleep disorder (obstructive sleep apnea, restless leg syndrome, narcolepsy, current or history of)
• Hospitalized or acutely ill
• Major Depression (current or history of)
• Lung transplant recipient

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Single; Slow-paced respiration therapy	Other: Slow-paced respiration therapy; The FDA-approved RESPeRATE device contains headphones and a sensor that attaches to the chest to detect inhalation and exhalation. Musical tones synchronize with the respiratory cycle to slowly guide the user to decrease respirations.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adherence to slow-paced respiration therapy.	Adherence rates will be assessed by the frequency of days used.	10 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in baseline and Week 10 dyspnea scores on the Multidimensional Dyspnea Profile	Baseline and 10 weeks
Change in baseline and Week 10 fatigue scores on the Multidimensional Fatigue Inventory	Baseline and 10 weeks
Change in baseline and Week 10 sleep scores on the Pittsburgh Sleep Quality Index	Baseline and 10 weeks
Change in baseline and Week 10 norepinephrine levels	Baseline and 10 weeks
Change in baseline and Week 10 interleukin-6 levels	Baseline and 10 weeks
Change in baseline and Week 10 tumor necrosis factor-alpha levels	Baseline and 10 weeks
Change in baseline and Week 10 six minute walk test	Baseline and 10 weeks
Change in baseline and Week 10 right ventricular systolic pressure	Baseline and 10 weeks

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Lea Ann Matura, PhD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (ACTUAL): March 1, 2015
• Study Completion (ACTUAL): March 1, 2016

Study Registration Dates

• First Submitted: February 20, 2014
• First Submitted That Met QC Criteria: March 4, 2014
• First Posted (ESTIMATE): March 6, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): August 31, 2016
• Last Update Submitted That Met QC Criteria: August 29, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: fatigue; sleep; symptoms; pulmonary arterial hypertension; dyspnea
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Disease; Hypertension, Pulmonary; Hypertension; Syndrome; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension
• Other Study ID Numbers: Penn-SON