Pulmonary Arterial HypertensionNCT01520493
Peripheral Muscle Microcirculation and Exercise-induced Blood Flow Distribution in Pulmonary Arterial Hypertension
A study testing Submaximal exercises in people with Pulmonary Arterial Hypertension, run by Laval University at 2 sites in Canada.
Trial summary
Pulmonary artery hypertension (PAH) is a rare, severe disease, characterized by a progressive increase in pulmonary vascular resistance ultimately leading to right ventricular (RV) failure and premature death. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- Submaximal exercises
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesCanada
- Study dates
- Jun 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 Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- WHO functional class II-III idiopathic PAH patients;
- WHO functional class II-III PAH-SSc patients with hemodynamic assessment <6 months;
- sedentary healthy subjects;
- subjects with limited SSc (without PAH) individually matched for age, gender, height and weight.
Who cannot join
- unstable clinical condition (e.g. recent syncope, WHO functional class IV);
- a six-minute walked distance < 300 meters during routine follow-up at the pulmonary hypertension clinic;
- left ventricular ejection fraction < 40%;
- restrictive (lung fibrosis on CT scan or total lung capacity < 80% of predicted) or obstructive lung disease (FEV1/FVC < 70%);
- contraindication for MRI;
- body mass index > 30 kg/m2;
- known locomotor abnormality.
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ)
Québec, G1V 4G5
Institut universitaire de cardiologie et de pneumologie de Québec
Québec, G1V 4G5
About this study
Pulmonary artery hypertension (PAH) is a rare, severe disease, characterized by a progressive increase in pulmonary vascular resistance ultimately leading to right ventricular (RV) failure and premature death. PAH may be idiopathic (IPAH) or may be also related to various conditions like portal hypertension, HIV infection, left to right shunt, connective tissue diseases such as scleroderma (PAHSSc). Symptoms include dyspnea and fatigue resulting in restricted exercise capacity and poor quality of life. The therapies currently approved have been shown to improve survival. Indeed, recent studies described a three year survival higher than 80%. This improved survival is associated with major challenges for clinicians as most patients remain with limited exercise capacity and poor quality of life. A clear understanding of exercise physiopathology is thus mandatory to specifically address mechanisms responsible for this exercise limitation and eventually improve patients' management. In order to better characterize the exercise physiopathology in PAH, the general objective of this research is to systematically examine blood flow distribution and limb muscles microcirculation at rest and during submaximal exercise in PAH.
Read the detailed description
Pulmonary artery hypertension (PAH) is a rare, severe disease, characterized by a progressive increase in pulmonary vascular resistance ultimately leading to right ventricular (RV) failure and premature death. PAH may be idiopathic (IPAH) or may be also related to various conditions like portal hypertension, HIV infection, left to right shunt, connective tissue diseases such as scleroderma (PAHSSc). PAH is defined as a mean pulmonary artery pressure (mPAP) of > 25 mmHg at rest. Symptoms include dyspnea and fatigue resulting in restricted exercise capacity and poor quality of life. The agents currently approved for treatment of PAH are prostanoids (i.v. epoprostenol or s.c./i.v. treprostinil), endothelin-receptor antagonists (ambrisentan, bosentan and sitaxsentan), and phosphodiesterase type 5-inhibitors (sildenafil and tadalafil). These therapies have been shown to improve pulmonary hemodynamics, exercise capacity, quality of life and survival. Indeed, recent studies described a three year survival higher than 80%. This improved survival is associated with major challenges for clinicians as most patients remain with limited exercise capacity and poor quality of life. A clear understanding of exercise physiopathology is thus mandatory to specifically address mechanisms responsible for this exercise limitation and eventually improve patients' management.
In order to better characterize the exercise physiopathology in PAH, the general objective of this research is to systematically examine blood flow distribution and limb muscles microcirculation at rest and during submaximal exercise in PAH. The limited link between traditional measures of pulmonary hemodynamic impairment and functional capacity confirms that exercise physiopathology in PAH is not well understood. Although peripheral muscle dysfunction and exercise intolerance are certainly multifactorial in origin and are unlikely to be explained by a single mechanism, an altered skeletal muscle microcirculation could represent a unifying mechanism to explain similarities in skeletal muscle dysfunction and exercise intolerance in PAH. The investigators plan to use a multimodality approach to provide comprehensive information regarding skeletal muscle perfusion in PAH. For example, the investigators will be able to know if there is some relationship between muscle perfusion heterogeneity (arterial spin labeling MRI) and microvascular oxygenation or muscle oxygen consumption (NIRS). Muscle oxygen delivery could also be influenced by cardiac function or hypoxemia. These methods should thus be viewed as complimentary and will help to separate differences in cardiac function, quadriceps global perfusion, perfusion heterogeneity and oxygenation and their consequences on skeletal muscle function and exercise tolerance in PAH versus controls.
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- Submaximal exercises
- Keywords
- pulmonary arterial hypertension, skeletal muscle microcirculation, exercise induced blood flow
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Submaximal exercisesOther
Consists of a 3-min unloaded exercise, followed by a progressive RAMP protocol (10 watts/min) up to 70% of peak workload followed by 3 min. of cycling at constant workload (70% peak workload) (total exercise duration of 25 min.).
| Study group | Role | What they receive |
|---|---|---|
| Exercise | Experimental | All patients are subject to this Arm. Receives: Other: Submaximal exercises |
What is being measured
The primary outcome is the main question the study is designed to answer.
Muscle microcirculation during submaximal exercise
Thigh muscles overall perfusion and perfusion heterogeneity will be assessed by pulsed arterial spin labeling magnetic resonance imaging (ASL MRI). MRI allows the acquisition of both spatially and temporally localized perfusion measurements within working muscle.
Measured: day 3
Cardiac output during submaximal exercise
Cardiac MRI. Right after muscles perfusion heterogeneity assessment by MRI (both at rest and following the same exercise protocol), cardiac MRI will be performed with the same 1.5 Tesla MRI.
Measured: day 3
Muscle sympathetic nerve activity (MSNA)
MSNA will be assessed by microneurography and measures sympathetic nerve traffic directed to muscle circulation. All measurements will be performed under quiet resting supine conditions before non-MRI exercise.
Measured: day 2
Quadriceps muscle function
Quadriceps muscle function will be assessed using voluntary and non-volitional measurements:
Strength of the dominant quadriceps will be evaluated using the Biodex System 4 Pro (Biodex Medical Systems, 20 Ramsay Road, Shirley, New York).
Non-volitional dominant quadriceps endurance will be evaluated by magnetic stimulation of the femoral nerve using the Magstim Rapid 2 system (Magstim Co. Ltd., Whitland, Dyfed, Wales, UK) coupled with the Biodex System 4 Pro, allowing measurements of intrinsic muscle endurance properties independent of central drive.
Measured: day 2
Relationship between in vivo muscle microcirculation and capillarity
Capillarity and angiogenesis-related gene expression in muscle biopsy. In order to explore the relationship between in vivo muscle microcirculation and capillarity, percutaneous biopsy specimens of the vastus lateralis muscle of the nondominant leg will be taken at midthigh as described by Bergström.
Measured: day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2012 (estimated)
- Study startJun 2011
- Primary completionAug 2013
- Study completionMar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- 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
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Laval University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Steeve Provencher, Laval University
- Investigators
- Steeve Provencher, MD, MSc, Principal investigator, Fondation IUCPQ
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01520493
- Sponsor's protocol ID
- Microcirculation_Local funds
- Status last verified
- Mar 2018
- First submitted
- 25 Jan 2012
- Last updated
- 7 Mar 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Peripheral Muscle Microcirculation and Exercise-induced Blood Flow Distribution in Pulmonary Arterial Hypertension
- ClinicalTrials.gov ID
- NCT01520493
- Acronym / sponsor ID
- Microcirculation_Local funds
- Conditions
- Pulmonary Arterial Hypertension
- Keywords
- pulmonary arterial hypertension, skeletal muscle microcirculation, exercise induced blood flow
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Laval UniversityUniversity, hospital or other
- Study start
- Jun 2011
- Primary completion
- Aug 2013 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 30 Jan 2012 (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 artery hypertension (PAH) is a rare, severe disease, characterized by a progressive increase in pulmonary vascular resistance ultimately leading to right ventricular (RV) failure and premature death. PAH may be idiopathic (IPAH) or may be also related to various conditions like portal hypertension, HIV infection, left to right shunt, connective tissue diseases such as scleroderma (PAHSSc). Symptoms include dyspnea and fatigue resulting in restricted exercise capacity and poor quality of life. The therapies currently approved have been shown to improve survival. Indeed, recent studies described a three year survival higher than 80%. This improved survival is associated with major challenges for clinicians as most patients remain with limited exercise capacity and poor quality of life. A clear understanding of exercise physiopathology is thus mandatory to specifically address mechanisms responsible for this exercise limitation and eventually improve patients' management. In order to better characterize the exercise physiopathology in PAH, the general objective of this research is to systematically examine blood flow distribution and limb muscles microcirculation at rest and during submaximal exercise in PAH.
Detailed description
Pulmonary artery hypertension (PAH) is a rare, severe disease, characterized by a progressive increase in pulmonary vascular resistance ultimately leading to right ventricular (RV) failure and premature death. PAH may be idiopathic (IPAH) or may be also related to various conditions like portal hypertension, HIV infection, left to right shunt, connective tissue diseases such as scleroderma (PAHSSc). PAH is defined as a mean pulmonary artery pressure (mPAP) of > 25 mmHg at rest. Symptoms include dyspnea and fatigue resulting in restricted exercise capacity and poor quality of life. The agents currently approved for treatment of PAH are prostanoids (i.v. epoprostenol or s.c./i.v. treprostinil), endothelin-receptor antagonists (ambrisentan, bosentan and sitaxsentan), and phosphodiesterase type 5-inhibitors (sildenafil and tadalafil). These therapies have been shown to improve pulmonary hemodynamics, exercise capacity, quality of life and survival. Indeed, recent studies described a three year survival higher than 80%. This improved survival is associated with major challenges for clinicians as most patients remain with limited exercise capacity and poor quality of life. A clear understanding of exercise physiopathology is thus mandatory to specifically address mechanisms responsible for this exercise limitation and eventually improve patients' management.
In order to better characterize the exercise physiopathology in PAH, the general objective of this research is to systematically examine blood flow distribution and limb muscles microcirculation at rest and during submaximal exercise in PAH. The limited link between traditional measures of pulmonary hemodynamic impairment and functional capacity confirms that exercise physiopathology in PAH is not well understood. Although peripheral muscle dysfunction and exercise intolerance are certainly multifactorial in origin and are unlikely to be explained by a single mechanism, an altered skeletal muscle microcirculation could represent a unifying mechanism to explain similarities in skeletal muscle dysfunction and exercise intolerance in PAH. The investigators plan to use a multimodality approach to provide comprehensive information regarding skeletal muscle perfusion in PAH. For example, the investigators will be able to know if there is some relationship between muscle perfusion heterogeneity (arterial spin labeling MRI) and microvascular oxygenation or muscle oxygen consumption (NIRS). Muscle oxygen delivery could also be influenced by cardiac function or hypoxemia. These methods should thus be viewed as complimentary and will help to separate differences in cardiac function, quadriceps global perfusion, perfusion heterogeneity and oxygenation and their consequences on skeletal muscle function and exercise tolerance in PAH versus controls.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Exercise | Experimental | Other: Submaximal exercisesAll patients are subject to this Arm. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- WHO functional class II-III idiopathic PAH patients;
- WHO functional class II-III PAH-SSc patients with hemodynamic assessment <6 months;
- sedentary healthy subjects;
- subjects with limited SSc (without PAH) individually matched for age, gender, height and weight.
Key exclusion criteria (7 listed)
- unstable clinical condition (e.g. recent syncope, WHO functional class IV);
- a six-minute walked distance < 300 meters during routine follow-up at the pulmonary hypertension clinic;
- left ventricular ejection fraction < 40%;
- restrictive (lung fibrosis on CT scan or total lung capacity < 80% of predicted) or obstructive lung disease (FEV1/FVC < 70%);
- contraindication for MRI;
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 |
|---|---|---|
| Submaximal exercisesConsists of a 3-min unloaded exercise, followed by a progressive RAMP protocol (10 watts/min) up to 70% of peak workload followed by 3 min. of cycling at constant workload (70% peak workload) (total exercise duration of 25 min.). | Other | Exercise |
Primary outcome
Muscle microcirculation during submaximal exercise
Time frame: day 3
Thigh muscles overall perfusion and perfusion heterogeneity will be assessed by pulsed arterial spin labeling magnetic resonance imaging (ASL MRI). MRI allows the acquisition of both spatially and temporally localized perfusion measurements within working muscle.
Cardiac output during submaximal exercise
Time frame: day 3
Cardiac MRI. Right after muscles perfusion heterogeneity assessment by MRI (both at rest and following the same exercise protocol), cardiac MRI will be performed with the same 1.5 Tesla MRI.
Muscle sympathetic nerve activity (MSNA)
Time frame: day 2
MSNA will be assessed by microneurography and measures sympathetic nerve traffic directed to muscle circulation. All measurements will be performed under quiet resting supine conditions before non-MRI exercise.
Quadriceps muscle function
Time frame: day 2
Quadriceps muscle function will be assessed using voluntary and non-volitional measurements: Strength of the dominant quadriceps will be evaluated using the Biodex System 4 Pro (Biodex Medical Systems, 20 Ramsay Road, Shirley, New York). Non-volitional dominant quadriceps endurance will be evaluated by magnetic stimulation of the femoral nerve using the Magstim Rapid 2 system (Magstim Co. Ltd., Whitland, Dyfed, Wales, UK) coupled with the Biodex System 4 Pro, allowing measurements of intrinsic muscle endurance properties independent of central drive.
Relationship between in vivo muscle microcirculation and capillarity
Time frame: day 1
Capillarity and angiogenesis-related gene expression in muscle biopsy. In order to explore the relationship between in vivo muscle microcirculation and capillarity, percutaneous biopsy specimens of the vastus lateralis muscle of the nondominant leg will be taken at midthigh as described by Bergström.
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 7 Mar 2018.
Related trials for Pulmonary Arterial Hypertension
RecruitingObservational study
Asthma and Primary Arterial Hypertension: an Inflammatory Link?
Asthma Bronchial
RecruitingPhase 1/2
HS235 Study in Overweight and Obese Participants With Combined Pre and Post-Capillary Pulmonary Hypertension Due to Heart Failure With Preserved Ejection Fraction
Pulmonary Hypertension, Heart Failure With Preserved Ejection Fraction
RecruitingPhase 2
Spironolactone for Pulmonary Arterial Hypertension
Pulmonary Arterial Hypertension
RecruitingPhase 1/2
A Study of HS235 for Treatment of Pulmonary Arterial Hypertension (PAH) in Adults
Pulmonary Arterial Hypertension
Active, not recruitingPhase 1
Study of Intravenous ZMA001 in Healthy Subjects
Pulmonary Arterial Hypertension PAH
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.
Steeve Provencher, MD, MSc principal investigator
Fondation IUCPQ
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Submaximal exercises in people with Pulmonary Arterial Hypertension, run by Laval University at 2 sites in Canada.
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 7 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 7 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. 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?
Muscle microcirculation during submaximal exercise (time frame: day 3). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Mar 2018.