Xenon PAH Bio: 129 Xenon MRI as a Biomarker for Diagnosis and Response to Therapy in Pulmonary Arterial Hypertension (PAH)
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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:
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Frequency of Adverse Events (AE) and/or Serious Adverse Events (SAE)
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Withdrawals due to adverse event or death
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Incidence of Adverse Events of Significant Interest (AESI):
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Electrocardiogram and any findings
-
Physical examination and vital signs
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: Idiopathic Pulmonary Arterial Hypertension Arm 1... patients with IPAH |
Drug: 129Xe Hyperpolarized
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
|
| Other: Pulmonary Arterial Hypertension Associated with Connective Tissue Disease Arm 2... patients with CTD-PAH |
Drug: 129Xe Hyperpolarized
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
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
Arm 1 -IPAH
-
Age: 18-75 years
-
WHO functional class 2 or 3
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Mean pulmonary artery pressures > 20 mmHg
-
Pulmonary capillary wedge pressure ≤15 mmHg
-
Pulmonary vascular resistance > 2 Wood Units (WU)
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No other cause identified for PAH
Arm 2 -PAH-CTD
-
Age: 18-75 years
-
WHO functional class (FC) 2 or 3
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Duke University Medical Center | Durham | North Carolina | United States | 27710 |
Sponsors and Collaborators
- Bastiaan Driehuys
- American Heart Association
Investigators
- Principal Investigator: Fawaz Alenezi, MD, Duke Univeristy
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Pro00113893