Cardiopulmonary Exercise Testing to Evaluate Pulmonary AVMs

September 25, 2023 updated by: Imperial College London

Hypoxemia, Dyspnea, and Exercise Tolerance in Patients With Pulmonary Arteriovenous Malformations

Pulmonary arteriovenous malformations (PAVMs) are a rare vascular condition affecting the lungs. PAVMs lead to low blood oxygen levels, yet are very well tolerated by patients. This study will examine the exercise capacity of PAVM patients using formal cardiopulmonary exercise tests performed on a stationary bicycle.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

It is well known that the lung is the site at which oxygen enters the blood stream, diffusing from the alveolar air sacs into the pulmonary capillaries. This newly oxygenated blood is carried to the heart in the pulmonary veins, then passes into the systemic circulation to provide oxygen to the tissues.

Patients with pulmonary arteriovenous malformations (PAVMs) have abnormal vascular connections between pulmonary arteries and pulmonary veins in the lung. Blood flowing through PAVMs therefore bypasses the oxygenation sites in the pulmonary capillaries. Low blood oxygen levels (hypoxemia) is frequent in PAVM patients but breathlessness (dyspnea) is not. The investigators have shown that dyspnea was not a common presenting complaint in a large UK series, and that there is little correlation between severity of dyspnea in PAVM patients, and blood oxygen levels.

In this study the investigators will address the question "Why are hypoxemic PAVM patients not more dyspneic?"

The investigators will address this by first performing standardised cardiopulmonary exercise testing, as used in the clinic, on age and sex matched patients with PAVMs and healthy controls. Physiological parameters will be compared, to test the null hypothesis that the impact of exercise on PAVM patients' cardiopulmonary systems does not differ to normal controls.

If the expected differences are confirmed, the investigators will examine if there is any difference to normals by re-examining the exercise tolerance of the PAVM cohort after they have had their PAVMs treated by embolization.

Most patients with PAVMs have an underlying hereditary vascular disorder, hereditary haemorrhagic telangiectasia. Assuming the expected differences between PAVM patients and controls are confirmed, the investigators will therefore also examine which pattern HHT patients without PAVMs display. Finally, cellular and molecular methods will be used to dissect mechanistic pathways.

Study Type

Interventional

Enrollment (Actual)

39

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United Kingdom
      • London, United Kingdom, W12 0NN
        • Hammersmith Hospital, Du Cane Rd

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Ability to provide informed consent
  • Healthy volunteers: no concurrent health reason to avoid exercise
  • Pulmonary AVMs: pulmonary AVMs confirmed by CT scan
  • Hereditary hemorrhagic telangiectasia without pulmonary AVMs: HHT according to current international consensus criteria, with no evidence of PAVMs on dedicated thoracic CT scan.

Exclusion Criteria:

  • Inability to provide informed consent.
  • Any known cardiovascular abnormality including a history of syncope (faintness, dizziness, lightheadedness or loss of consciousness due to an abnormality of the cardiovascular system).
  • Current respiratory tract infection (eg a cold).
  • Pregnancy.
  • Claustrophobia or needle phobia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Healthy control
A group of up to 30 healthy controls will be recruited to have a cardiopulmonary exercise test and a blood test.
Other: Cardiopulmonary exercise test
On Day 1, subjects will have the test in the Exercise Suite of Hammersmith Hospital, London, UK. They will have painless skin probes placed on their fingers, chest, and legs to monitor heart rate, ECG, blood oxygen levels, and oxygen delivery during the test. Subjects will also be shown how to breathe through a mouthpiece with a nose clip on, and how to indicate on a sliding device whether they feel breathless. They will then start cycling against a very low resistance at a steady speed. As long as they feel comfortable, there will be a gradual increase in work load until they feel they cannot keep going at the same speed. They can also stop sooner for any reason. Afterwards, while they are "cooling down" (within the hour on Day 1), they will fill in a short questionnaire describing how they feel.
Procedure: Blood test
On same day (Day 1), the subject will have 20-30mls of blood (that is, 4-6 teaspoonful) taken for analysis.
Experimental: Pulmonary AVM
A group of up to 30 pulmonary AVM patients will be recruited to have a cardiopulmonary exercise test, and a blood test.
Other: Cardiopulmonary exercise test
On Day 1, subjects will have the test in the Exercise Suite of Hammersmith Hospital, London, UK. They will have painless skin probes placed on their fingers, chest, and legs to monitor heart rate, ECG, blood oxygen levels, and oxygen delivery during the test. Subjects will also be shown how to breathe through a mouthpiece with a nose clip on, and how to indicate on a sliding device whether they feel breathless. They will then start cycling against a very low resistance at a steady speed. As long as they feel comfortable, there will be a gradual increase in work load until they feel they cannot keep going at the same speed. They can also stop sooner for any reason. Afterwards, while they are "cooling down" (within the hour on Day 1), they will fill in a short questionnaire describing how they feel.
Procedure: Blood test
On same day (Day 1), the subject will have 20-30mls of blood (that is, 4-6 teaspoonful) taken for analysis.
Experimental: HHT but no pulmonary AVM
Most patients with pulmonary AVMs have underlying hereditary hemorrhagic telangiectasia (HHT). If there is a difference between pulmonary AVM and control groups that does not correct following embolization of pulmonary AVMs, a group of up to 30 people with HHT but no evidence of pulmonary AVMs will be selected to have a cardiopulmonary exercise test and a blood test.
Other: Cardiopulmonary exercise test
On Day 1, subjects will have the test in the Exercise Suite of Hammersmith Hospital, London, UK. They will have painless skin probes placed on their fingers, chest, and legs to monitor heart rate, ECG, blood oxygen levels, and oxygen delivery during the test. Subjects will also be shown how to breathe through a mouthpiece with a nose clip on, and how to indicate on a sliding device whether they feel breathless. They will then start cycling against a very low resistance at a steady speed. As long as they feel comfortable, there will be a gradual increase in work load until they feel they cannot keep going at the same speed. They can also stop sooner for any reason. Afterwards, while they are "cooling down" (within the hour on Day 1), they will fill in a short questionnaire describing how they feel.
Procedure: Blood test
On same day (Day 1), the subject will have 20-30mls of blood (that is, 4-6 teaspoonful) taken for analysis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total body oxygen consumption in mls/min/kg, at peak exercise (VO2 max).
Time Frame: Same day (Day 1), at end of exercise study
Of the many measurements and derived indices that can be measured during cardiopulmonary exercise testing, the peak consumption of oxygen (VO2 max) is perhaps the best indicator of integrated cardiorespiratory capacity. The principle research question will therefore test the null hypothesis that "The VO2 max does not differ between PAVM patients and age matched healthy controls."
Same day (Day 1), at end of exercise study

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Breathing reserve (%)
Time Frame: Same day (Day 1) at end of exercise test
We will also test in univariate and multiple regression analyses whether breathing reserve differs between PAVM patients and controls.
Same day (Day 1) at end of exercise test
Ventilatory efficiency, derived from the VE / CO2 slope (L/min/L/min)
Time Frame: Same day (Day 1), at end of exercise study
We will also test in univariate and multiple regression analyses whether ventilatory efficiency differs between PAVM patients and controls.
Same day (Day 1), at end of exercise study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Imperial College London

Investigators

  • Principal Investigator: Claire L Shovlin, Imperial College London

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2011

Primary Completion (Actual)

March 1, 2015

Study Completion (Actual)

March 1, 2015

Study Registration Dates

First Submitted

October 16, 2012

First Submitted That Met QC Criteria

May 1, 2015

First Posted (Estimated)

May 6, 2015

Study Record Updates

Last Update Posted (Actual)

September 28, 2023

Last Update Submitted That Met QC Criteria

September 25, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLS/22
  • 11/H0803/9 (Other Identifier: National Research Ethics Service, UK)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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