Peripheral Muscle Microcirculation and Exercise-induced Blood Flow Distribution in Pulmonary Arterial Hypertension

NCT01520493 | Completed

• 1 other identifier: Microcirculation_Local funds
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Pulmonary Arterial Hypertension

Keywords

pulmonary arterial hypertension; skeletal muscle microcirculation; exercise induced blood flow

Outcome Measures

Primary Outcomes (5)

• 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.

  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.

  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.

  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.

  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.

  day 1

Study Arms (1)

Exercise

EXPERIMENTAL

All patients are subject to this Arm.

Other: Submaximal exercises

Interventions

Submaximal exercises OTHER

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.).

Exercise

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Laval University: lead

Study Sites (2)

Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ)

Québec, G1V 4G5, Canada

Location

Institut universitaire de cardiologie et de pneumologie de Québec

Québec, G1V 4G5, Canada

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Steeve Provencher, MD, MSc

  Fondation IUCPQ

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professeur

Study Record Dates

• First Submitted: January 25, 2012
• First Posted: January 30, 2012
• Study Start: June 1, 2011
• Primary Completion: August 1, 2013
• Study Completion: March 1, 2015
• Last Updated: March 7, 2018

Record last verified: 2018-03

Locations

CA (2)