Dyspnea in Chronic Thromboembolic Pulmonary Hypertension

NCT03786367 | Completed

• 1 other identifier: DMED-2208-18
• Study Type: observational
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

Pulmonary embolism, or clots blocking the blood vessels of the lungs, is a common clinical condition requiring treatment with blood thinners. In most patients, recovery is complete. A small proportion of patients, however, develop complications (high blood pressure in the lung circulation, i.e. pulmonary hypertension). Persisting breathlessness during activity is a common symptom in many of these patients and leads to a reduced ability to engage in daily physical activity. The reason for this activity-related breathlessness remains uncertain and is the main question of the proposed study. Using new sophisticated technology, the investigators will determine the root causes of perceived breathing difficulty. The investigators will test the idea that breathlessness is fundamentally the result of increased drive to breathe from control centers in the brain. The investigators will measure drive to breathe by measuring the electrical activity descending from the brain to the main muscle of breathing - the diaphragm. The investigators will discover if the increased drive to breathe is due to accumulation of carbon dioxide in the blood as a result of poor blood perfusion of areas of the lung due to the effects of blockage by clots. The investigators also will investigate whether weakness and fatigue of the muscles of breathing, as a result of the high breathing demands that are present in patients with blood clots in the lungs, contribute to breathlessness. With this information it is hopeful that better treatment options will be developed to relieve this distressing symptom.

Conditions

Chronic Thromboembolic Pulmonary Hypertension

Keywords

Dyspnea; Exertional Dyspnea; Pulmonary Hypertension; Exercise

Outcome Measures

Primary Outcomes (2)

• Diaphragm electromyography (EMGdi) at a standardized time during cycle exercise test

  EMGdi will be used as an index of inspiratory neural drive. Assessments will be compared at a standardized time (at rest, during isotime and end-exercise) during incremental cycle ergometer exercise test.

  Conducted at visit 2, 2-7 days after screening visit

• Dyspnea intensity measured by the 10-point Borg Scale at a standardized time during cycle exercise test

  The 10-point Borg scale ranges from 0 "nothing at all" to 10 "maximal/extremely strong" and will be used to rate the intensity of dyspnea during exercise: a decrease in this rating signifies an improvement. Dyspnea intensity will be assessed at a standardized time (every minute) during incremental cycle ergometer exercise test.

  Conducted at visit 2, 2-7 days after screening visit

Secondary Outcomes (5)

• Inspiratory Capacity at a standardized time during cycle exercise test

  Conducted at visit 2, 2-7 days after screening visit

• Ventilation at a standardized time during cycle exercise test

  Conducted at visit 2, 2-7 days after screening visit

• Breathing frequency at a standardized time during cycle exercise test.

  Conducted at visit 2, 2-7 days after screening visit

• Carbon dioxide output (VCO2) at a standardized time during cycle exercise test.

  Conducted at visit 2, 2-7 days after screening visit

• Maximal oxygen uptake (VO2) at a standardized time during cycle exercise test.

  Conducted at visit 2, 2-7 days after screening visit

Study Arms (2)

CTEPH

Clinically stable patients with Chronic Thromboembolic Pulmonary Hypertension (CTEPH) recruited from the Pulmonary Hypertension outpatient clinics at Hotel Dieu Hospital, Kingston, Ontario.

Control

Age and sex-matched healthy control data collected as part of previous studies will be used as historic controls for this study.

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Subjects will include 20 clinically stable patients with Chronic Thromboembolic Pulmonary Hypertension (CTEPH) recruited from the Pulmonary Hypertension outpatient clinics at Hotel Dieu Hospital, Kingston, Ontario. Healthy Control data will be from previous studies (no additional testing required in this group).

You may qualify if:

• clinically stable as defined by stable hemodynamic status, optimized medical treatment, no changes in medication dosage or frequency of administration with no hospital admissions in the preceding 6 weeks
• male or female ≥40 years of age
• non-smoker
• moderate-to-severe chronic activity-related dyspnea as defined by a modified Medical Research Council (MRC) dyspnea scale ≥2, or Baseline Dyspnea Index focal score ≤ 6
• ability to perform all study procedures and provide/sign informed consent.

You may not qualify if:

• women of childbearing age who are pregnant or trying to become pregnant
• active cardiopulmonary disease or other comorbidities that could contribute to dyspnea and exercise limitation
• important contraindications to clinical exercise testing, including inability to exercise because of neuromuscular or musculoskeletal disease(s)
• use of daytime oxygen or exercise-induced O2 desaturation to \< 80% on room air
• body mass index (BMI) \<18.5 or ≥35.0 kg/m2
• other causes of significant pulmonary hypertension: pulmonary arterial hypertension, left heart disease, chronic pulmonary disease including, obstructive sleep apnea or pulmonary hypertension of unclear or multifactorial mechanism
• systemic connective tissue disease

Sponsors & Collaborators

• Dr. Denis O'Donnell: lead
• Queen's University: collaborator

Study Sites (1)

Respiratory Investigation Unit, Kingston General Hospital

Kingston, Ontario, K7L 2V7, Canada

Location

Related Publications (1)

• Faisal A, Alghamdi BJ, Ciavaglia CE, Elbehairy AF, Webb KA, Ora J, Neder JA, O'Donnell DE. Common Mechanisms of Dyspnea in Chronic Interstitial and Obstructive Lung Disorders. Am J Respir Crit Care Med. 2016 Feb 1;193(3):299-309. doi: 10.1164/rccm.201504-0841OC.

  PMID: 26407036 BACKGROUND

MeSH Terms

Conditions

Dyspnea; Hypertension, Pulmonary; Motor Activity

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Lung Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Behavior

Study Officials

• Denis E O'Donnell, MD

  Respiratory Investigation Unit, Queen's University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 15, 2018
• First Posted: December 26, 2018
• Study Start: November 1, 2018
• Primary Completion: September 30, 2022
• Study Completion: January 1, 2023
• Last Updated: April 13, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)