Observational Study of Actigraphy in Pediatric Pulmonary Arterial Hypertension

A Prospective Study to Investigate the Use of Actigraphy as a Novel, Reliable and Non-invasive Study Endpoint to Facilitate Pediatric Pulmonary Arterial Hypertension Trials and Drug Development for Children Ages 0-6 Years

This study plans to learn more about activity levels in children with pulmonary hypertension. Pulmonary hypertension is a condition where the pressure in the lungs is higher than normal. This can affect the person's heart. The purpose of this study is to see if measuring activity in children with pulmonary hypertension and comparing it to activity in children without pulmonary hypertension can give their doctor helpful information on how they are feeling and how their treatment is working.

Study Overview

• Status: Completed
• Conditions: Hypertension;Pulmonary;Primary

• Study Type: Observational
• Enrollment (Actual): 43

Contacts and Locations

• Study Contact: Name: Clinical Research Coordinator; Phone Number: 720-777-8669; Email: Suzette.mattoch@childrenscolorado.org

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 6 years (Child)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

PH patients of PIs seen in cardiology clinics, and a community sample of healthy control participants

Description

Inclusion criteria for children with PAH:

1. Ages 0-6 years at the time of consent
2. Current diagnosis of pulmonary hypertension in World Health Organization (WHO) Diagnostic Group 1 as per established clinical criteria including prior catheterization meeting Group 1 criteria
3. Panama Functional Class II-IIIa
4. Must have been receiving an approved oral endothelin receptor antagonist, calcium channel blocker, phosphodiesterase 5 inhibitor, prostanoid and/or soluble guanylate cyclase stimulator for at least 30 days prior to consent, and has been at the current stable dose, other than weight-based adjustments, for at least 30 days prior to consent
5. On stable doses of other medical therapy for 14 days prior to enrollment visit with no dose adjustments, additions, or discontinuations (exception diuretics and anticoagulants; OTC/cold/seasonal allergy medications).

Exclusion criteria for children with PAH:

1. Diagnosis of congenital diaphragmatic hernia, or a chronic lung disease, such as bronchopulmonary dysplasia, or interstitial lung disease
2. Any bone (e.g., osteogenesis imperfecta, ankle, knee, or hip injuries), neuromuscular (e.g., muscular dystrophy), or other pathology that may limit activity (e.g., arthritis)
3. Down syndrome
4. Use of any medications known to limit activity (e.g., sedative)
5. Active infection (may re-screen for enrollment once resolved)

6. Any other cardiovascular, liver, renal, hematologic, gastrointestinal, immunologic, endocrine, metabolic, or central nervous system disease or condition that, in the opinion of the Investigator, may adversely affect the safety of the participant or interfere with the interpretation of study assessments

   Examples:

   1. Current diagnosis of uncontrolled sleep apnea as defined by their physician
   2. Severe renal insufficiency as defined by the requirement for dialysis at screening
   3. Moderate to severe hepatic dysfunction defined as elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) liver function tests, greater than or equal to three times the upper limit of normal at screening
7. Actively listed for transplantation
8. Patient and/or legal guardian has/have an unstable psychiatric condition or is/are mentally incapable of understanding the objectives, nature, or consequences of the trial, or has any condition in which the Investigator's opinion would constitute an unacceptable risk to the participant's safety

Inclusion criteria for control children:

1. Ages 0-6 years at the time of consent
2. In good general health as evidenced by medical history reported by parent/legal guardian during screening and/or available medical records

Exclusion criteria for control children:

1. Known diagnosis of asthma (controlled or uncontrolled)
2. Inability to exercise normally either due to an intellectual disability (e.g., Down Syndrome), or a physical disability which could impede activities of daily living.
3. Child and/or legal guardian has/have an unstable psychiatric condition or is/are mentally incapable of understanding the objectives, nature, or consequences of the trial, or has any condition in which the Investigator's opinion would constitute an unacceptable risk to the participant's safety

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Pulmonary Hypertension Participants; Children with Primary Pediatric Pulmonary Arterial Hypertension
Control Participants; Children with a healthy heart and lungs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Meeting Compliance threshold for wearing actigraphy devices: Visit 1	Actigraphy device wear compliance threshold is a minimum of 4 hours per day, and 8 compliant days out of 14 days of wear time.	Over 14 Days, reported at Day 15 post baseline (Visit 1)
Number of Participants Meeting Compliance threshold for wearing actigraphy devices: Visit 2	Actigraphy device wear compliance threshold is a minimum of 4 hours per day, and 8 compliant days out of 14 days of wear time.	Over 14 days, reported at about 6 months post-baseline (Visit 2)
Number of skin irritation adverse events: Visit 1		Over 14 Days, reported at Day 15 post baseline (Visit 1)
Number of skin irritation adverse events: Visit 2		Over 14 days, reported at about 6 months post-baseline (Visit 2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart rate: Visit 1	Measured via Fitbit.	Over 14 Days, reported at Day 15 post baseline (Visit 1)
Heart rate: Visit 2	Measured via Fitbit.	Over 14 days, reported at about 6 months post-baseline (Visit 2)
Steps per day: Visit 1	Measured via Fitbit and ActiGraph wGT3x-BT.	Over 14 Days, reported at Day 15 post baseline (Visit 1)
Steps per day: Visit 2	Measured via Fitbit and ActiGraph wGT3x-BT.	Over 14 days, reported at about 6 months post-baseline (Visit 2)
Miles per day: Visit 1	Measured via Fitbit.	Over 14 Days, reported at Day 15 post baseline (Visit 1)
Miles per day: Visit 2	Measured via Fitbit.	Over 14 days, reported at about 6 months post-baseline (Visit 2)
Energy expenditure per day (kcal): Visit 1	Measured via Fitbit and ActiGraph wGT3x-BT.	Over 14 Days, reported at Day 15 post baseline (Visit 1)
Energy expenditure per day (kcal): Visit 2	Measured via Fitbit and ActiGraph wGT3x-BT.	Over 14 days, reported at about 6 months post-baseline (Visit 2)
Active minutes per day: Visit 1	Measured via Fitbit.	Over 14 Days, reported at Day 15 post baseline (Visit 1)
Active minutes per day: Visit 2	Measured via Fitbit.	Over 14 days, reported at about 6 months post-baseline (Visit 2)
Count of Activity Bouts: Visit 1	Count of Active bouts recorded and defined by the Actigraphy devices.	Over 14 Days, reported at Day 15 post baseline (Visit 1)
Count of Activity Bouts: Visit 2	Count of Active bouts recorded and defined by the Actigraphy devices.	Over 14 days, reported at about 6 months post-baseline (Visit 2)
Count of Sedentary Bouts: Visit 1	Count of Sedentary Bouts recorded and defined by the Actigraphy devices.	Over 14 Days, reported at Day 15 post baseline (Visit 1)
Count of Sedentary Bouts: Visit 2	Count of Sedentary Bouts recorded and defined by the Actigraphy devices.	Over 14 days, reported at about 6 months post-baseline (Visit 2)
Activity Count: Visit 1	Count of Activity Events recorded and defined by the Actigraphy devices.	Over 14 Days, reported at Day 15 post baseline (Visit 1)
Activity Count: Visit 2	Count of Activity Events recorded and defined by the Actigraphy devices.	Over 14 days, reported at about 6 months post-baseline (Visit 2)
Physical Activity intensity: Visit 1	Number of minutes with "Mild", "Moderate", and "Vigorous" physical activity.	Over 14 Days, reported at Day 15 post baseline (Visit 1)
Physical Activity intensity: Visit 1	Number of minutes with "Mild", "Moderate", and "Vigorous" physical activity.	Over 14 days, reported at about 6 months post-baseline (Visit 2)
Resting oxygen saturation at Baseline		Baseline
Resting oxygen saturation at Visit 2		About 6 months post baseline
Number of PH Participants with Clinical Worsening (CW) Events		End of Study (Up to 12 months post baseline)
Number of PH Participants with Genetic Mutations or Positive Genetic tests	Count of PH participants with an observed positive genetic test or genetic mutation.	End of Study (Up to 12 months post baseline)
Natriuretic Peptide Tests - BNP	Brain natriuretic peptide (BNP): a heart failure marker	End of Study (Up to 12 months post baseline)
Natriuretic Peptide Tests - NT-proBNP)	N-terminal pro b-type natriuretic peptide (NT-proBNP): a heart failure marker	End of Study (Up to 12 months post baseline)

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: Children's Hospital Colorado; Food and Drug Administration (FDA)
• Investigators: Principal Investigator: Dunbar Ivy, MD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): February 11, 2021
• Primary Completion (Actual): April 14, 2022
• Study Completion (Actual): April 14, 2022

Study Registration Dates

• First Submitted: February 4, 2021
• First Submitted That Met QC Criteria: February 4, 2021
• First Posted (Actual): February 9, 2021

Study Record Updates

• Last Update Posted (Actual): May 10, 2023
• Last Update Submitted That Met QC Criteria: May 8, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Pediatric; PAH; Idiopathic
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Pulmonary Arterial Hypertension; Hypertension, Pulmonary
• Other Study ID Numbers: 20-2341; 75F40119C10090 (Other Grant/Funding Number: FDA_BAA-18-00123)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No