Pulmonary Arteriovenous MalformationsNCT02436213
Cardiopulmonary Exercise Testing to Evaluate Pulmonary AVMs
A study testing Cardiopulmonary exercise test and Blood test in people with Pulmonary Arteriovenous Malformations and Hereditary Hemorrhagic Telangiectasia, run by Imperial College London at 1 site in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Pulmonary Arteriovenous Malformations, Hereditary Hemorrhagic Telangiectasia
- What is being tested?
- Cardiopulmonary exercise test and Blood test
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Apr 2011to Mar 2015
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Being tested
- Cardiopulmonary exercise test, Blood test
- Keywords
- workload, oxygen level, oxygen consumption, breathing reserve, ventilatory efficiency
- Medical subject headings
- Telangiectasia, Hereditary Hemorrhagic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cardiopulmonary exercise testOther
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.
Blood testProcedure or surgery
On same day (Day 1), the subject will have 20-30mls of blood (that is, 4-6 teaspoonful) taken for analysis.
| Study group | Role | What they receive |
|---|---|---|
| Healthy control | Experimental | A group of up to 30 healthy controls will be recruited to have a cardiopulmonary exercise test and a blood test. Receives: Other: Cardiopulmonary exercise test; Procedure: Blood test |
| Pulmonary AVM | Experimental | A group of up to 30 pulmonary AVM patients will be recruited to have a cardiopulmonary exercise test, and a blood test. Receives: Other: Cardiopulmonary exercise test; Procedure: Blood test |
| HHT but no pulmonary AVM | Experimental | 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. Receives: Other: Cardiopulmonary exercise test; Procedure: Blood test |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total body oxygen consumption in mls/min/kg, at peak exercise (VO2 max).
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."
Measured: Same day (Day 1), at end of exercise study
Secondary outcomes (2)
Breathing reserve (%)
We will also test in univariate and multiple regression analyses whether breathing reserve differs between PAVM patients and controls.
Measured: Same day (Day 1) at end of exercise test
Ventilatory efficiency, derived from the VE / CO2 slope (L/min/L/min)
We will also test in univariate and multiple regression analyses whether ventilatory efficiency differs between PAVM patients and controls.
Measured: Same day (Day 1), at end of exercise study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2015 (estimated)
- Study startApr 2011
- Primary completionMar 2015
- Study completionMar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Arteriovenous MalformationsStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Claire L Shovlin, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02436213
- Sponsor's protocol ID
- CLS/22
- Other IDs
- 11/H0803/9
- Status last verified
- Sep 2023
- First submitted
- 16 Oct 2012
- Last updated
- 28 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
Publications
Howard LSGE, Santhirapala V, Murphy K, Mukherjee B, Busbridge M, Tighe HC, Jackson JE, Hughes JMB, Shovlin CL. Cardiopulmonary exercise testing demonstrates maintenance of exercise capacity in patients with hypoxemia and pulmonary arteriovenous malformations. Chest. 2014 Sep;146(3):709-718. doi: 10.1378/chest.13-2988.
PubMed 24676541Gawecki F, Strangeways T, Amin A, Perks J, McKernan H, Thurainatnam S, Rizvi A, Jackson JE, Santhirapala V, Myers J, Brown J, Howard LSGE, Tighe HC, Shovlin CL. Exercise capacity reflects airflow limitation rather than hypoxaemia in patients with pulmonary arteriovenous malformations. QJM. 2019 May 1;112(5):335-342. doi: 10.1093/qjmed/hcz023.
PubMed 30657990
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hypoxemia, Dyspnea, and Exercise Tolerance in Patients With Pulmonary Arteriovenous Malformations
- ClinicalTrials.gov ID
- NCT02436213
- Acronym / sponsor ID
- CLS/22
- Keywords
- workload, oxygen level, oxygen consumption, breathing reserve, ventilatory efficiency
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- Apr 2011 (actual)
- Primary completion
- Mar 2015 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 6 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Supportive care
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Healthy control | Experimental | Other: Cardiopulmonary exercise test, Procedure: Blood testA group of up to 30 healthy controls will be recruited to have a cardiopulmonary exercise test and a blood test. |
| Pulmonary AVM | Experimental | Other: Cardiopulmonary exercise test, Procedure: Blood testA group of up to 30 pulmonary AVM patients will be recruited to have a cardiopulmonary exercise test, and a blood test. |
| HHT but no pulmonary AVM | Experimental | Other: Cardiopulmonary exercise test, Procedure: Blood testMost 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cardiopulmonary exercise testOn 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. | Other | HHT but no pulmonary AVM, Healthy control, Pulmonary AVM |
| Blood testOn same day (Day 1), the subject will have 20-30mls of blood (that is, 4-6 teaspoonful) taken for analysis. | Procedure or surgery | HHT but no pulmonary AVM, Healthy control, Pulmonary AVM |
Primary outcome
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."
2 secondary outcomes
Breathing reserve (%)
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2023.
- Results publication: PubMed 24676541Howard LSGE, Santhirapala V, Murphy K, Mukherjee B, Busbridge M, Tighe HC, Jackson JE, Hughes JMB, Shovlin CL. Cardiopulmonary exercise testing demonstrates maintenance of exercise capacity in patients with hypoxemia and pulmonary arteriovenous malformations. Chest. 2014 Sep;146(3):709-718. doi: 10.1378/chest.13-2988.
- Results publication: PubMed 30657990Gawecki F, Strangeways T, Amin A, Perks J, McKernan H, Thurainatnam S, Rizvi A, Jackson JE, Santhirapala V, Myers J, Brown J, Howard LSGE, Tighe HC, Shovlin CL. Exercise capacity reflects airflow limitation rather than hypoxaemia in patients with pulmonary arteriovenous malformations. QJM. 2019 May 1;112(5):335-342. doi: 10.1093/qjmed/hcz023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Claire L Shovlin principal investigator
Imperial College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cardiopulmonary exercise test and Blood test in people with Pulmonary Arteriovenous Malformations and Hereditary Hemorrhagic Telangiectasia, run by Imperial College London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total body oxygen consumption in mls/min/kg, at peak exercise (VO2 max). (time frame: Same day (Day 1), at end of exercise study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02436213, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2023.