Connective Tissue Diseases, Idiopathic Pulmonary Arterial Hypertension, Pulmonary Arterial Hypertension, Pulmonary Arterial Hypertension Associated With Connective Tissue Disease (Disorder)
Conditions
Brief summary
The overall study objectives outlined in this study are to derive 129Xe MRI pulmonary vascular biomarker signatures that differentiate common subtypes of PAH and to determine the ability of 129Xe MRI to longitudinally monitor disease progression and response to therapy in PAH, with the aid of additional assessments, such as labs, echocardiography, and six-minute walk distance (6MWD).
Detailed description
Subject Enrollment This study will consent and enroll 20 subjects total. • For Arm 1, 10 subjects with Idiopathic Pulmonary Arterial Hypertension (IPAH) will be consented and enrolled. For Arm 2, 10 subjects with Connective Tissue Disease Associated Pulmonary Arterial Hypertension (PAH-CTD) will be consented and enrolled. Study Design This study will be observational. Subjects in both arms of the trial will undergo a 129Xe MRI/MRS at timepoints of baseline, 3 months, 6 months, and 12 months. In addition to the this, data from standard of care assessments, such as labs, echocardiography, and six-minute walk distance (6MWD), will also collected at these timepoints. Primary Study Endpoints The primary endpoint for this trial will be the change in defect + low percentage of RBC signal on hyperpolarized 129Xe MRI from baseline to 12 months Secondary Study Endpoints There will be several secondary endpoints for this trial: * Change in regional and global RBC Oscillation Amplitudes on hyperpolarized 129Xe MR spectroscopy from baseline to 12 months * Change in 6MWD from baseline to 12 months * Change in NTproBNP from baseline to 12 months * Change in WHO FC from baseline to 12 months Primary Safety Endpoints There will be several primary safety endpoints for this trial: * Frequency of Adverse Events (AE) and/or Serious Adverse Events (SAE) * Withdrawals due to adverse event or death * Incidence of Adverse Events of Significant Interest (AESI): * Electrocardiogram and any findings * Physical examination and vital signs
Interventions
Each xenon dose will be limited to a volume less than 25% of a subject's total lung capacity (TLC), as is the case for all protocols currently carried out under IND 109490
Sponsors
Bastiaan Driehuys
American Heart Association
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Arm 1 -IPAH * Age: 18-75 years * WHO functional class 2 or 3 * Mean pulmonary artery pressures \> 20 mmHg * Pulmonary capillary wedge pressure ≤15 mmHg * Pulmonary vascular resistance \> 2 Wood Units (WU) * No other cause identified for PAH Arm 2 -PAH-CTD * Age: 18-75 years * WHO functional class (FC) 2 or 3 * Mean pulmonary artery pressures \> 20 mmHg * Pulmonary capillary wedge pressure ≤15 mmHg * Pulmonary vascular resistance \> 2 WU * Diagnosis of connective tissue disease
Exclusion criteria
* PH other than Idiopathic PAH or PAH associated with CTD; any conditions that prevent the performance of 129Xe MRI scans will be excluded from the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pulmonary Vascular Remodeling | 1 year | The primary endpoint for this trial will be the change in defect + low percentage of RBC signal on hyperpolarized 129Xe MRI from baseline to 12 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| RBC Oscillation Amplitude | 1 year | • Change in regional and global RBC Oscillation Amplitudes on hyperpolarized 129Xe MR spectroscopy from baseline to 12 months |
| 6 Minute Walk Distance | 1 Year | Change in 6MWD from baseline to month 12 |
| NTproBNP | 1 year | Change in NTproBNP from baseline to month 12 |
| World Health Organization (WHO) Functional Class (FC) | 1 year | Change in WHO FC from baseline to month 12 |
Countries
United States
Contacts
CONTACTClaudia Salazar
PRINCIPAL_INVESTIGATORFawaz Alenezi, MD
Duke Univeristy
Outcome results
None listed