Ignite Creation Date:
2024-05-06 @ 8:22 PM
Last Modification Date:
2024-10-26 @ 3:26 PM
Study NCT ID:
NCT06351345
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-07-11
First Post:
2024-04-02
Brief Title:
129 Xenon Imaging in Patients Treated With Sotatercept
Sponsor:
Bastiaan Driehuys
Organization:
Duke University
Study Overview
Official Title:
129Xenon MR Imaging and Spectroscopy Response to Sotatercept in Pulmonary Arterial Hypertension
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Sox-PH
Brief Summary:
Determine the ability of 129Xe MRIMRS biomarker signatures to non-invasively monitor pulmonary vascular reverse remodeling induced by sotatercept in pulmonary arterial hypertension PAH
Detailed Description:
The researchers hypothesize that 129Xe MRIMRS biomarker signatures of pulmonary vascular remodeling will predict short- and long-term response and efficacy to PAH patients who are receiving sotatercept as clinical standard-of-care At baseline prior to the treatment with sotatercept 3 and 12 months of follow-up the research team will perform 129Xe MRIMRS scans 129Xe MRIMRS metrics including 1 129Xe MRI ventilation defect reflecting gas exchange abnormalities 2129Xe MRI RBC defect percentage reflecting pulmonary capillary blood volume 3 129Xe MRI membrane uptake percentage reflecting lung interstitial wall thick-ness and inflammation and 4 129Xe MRS oscillation amplitude reflecting degree of prepost-capillary PH as well as standard-of-care assessments including labs echocardiography NTproBNP and 6MWD will be acquired at each visit The investigators expect that 129Xe MRIMRS biomarker signatures will improve prediction of treatment response and clinical outcomes hospitalizations and death compared to standard risk assessment with functional class 6MWD and NTproBNP
This study would allow an assessment of sotatercepts role in promoting pulmonary vascular reverse remodeling It could also improve outcome assessment in clinical trials to a biomarker that is more accurate and precise thus allowing greater reliability in assessment of treatment effect and allowing smaller clinical trial size Lastly three-dimensional functional lung imaging could provide greater individualized assessment of lung function and tailoring of therapy thus optimizing precision and personalized medicine
PAH is characterized by obstructive vasculopathy of the pulmonary arterioles that results in right heart failure and death The pulmonary vascular remodeling in PAH includes neointimal proliferation medial hypertrophy plexiform arteriopathy and fibrosis these changes can also differ between these subtypes This results in specific changes in cardiac and pulmonary physiology most notably 1 an increase in the pulmonary vascular resistance PVR through the blood vessels due to their obstruction and 2 a decrease in sur-face area and capillary blood volume for gas exchange through disruption of the normal capillary-alveolar interface with a decrease in the diffusion limit for carbon monoxide DLCO The increase in PVR results in increased afterload on the right heart resulting in right ventricular RV dysfunction and failure Similarly gas exchange abnormalities contribute to decreased ventilatory efficiency and exercise limitation Current treatments which target the prostacyclin endothelin-1 or nitric oxide pathways slow disease progression However these drugs are thought to act largely through vasodilation and not through remodeling For that reason the 5-year survival rate in PAH is still only approximately 60 highlighting the need for therapies targeting pulmonary vascular remodeling pathways
This study would allow an assessment of sotatercepts role in promoting pulmonary vascular reverse remodeling It could also improve outcome assessment in clinical trials to a biomarker that is more accurate and precise thus allowing greater reliability in assessment of treatment effect and allowing smaller clinical trial size Lastly three-dimensional functional lung imaging could provide greater individualized assessment of lung function and tailoring of therapy thus optimizing precision and personalized medicine
PAH is characterized by obstructive vasculopathy of the pulmonary arterioles that results in right heart failure and death The pulmonary vascular remodeling in PAH includes neointimal proliferation medial hypertrophy plexiform arteriopathy and fibrosis these changes can also differ between these subtypes This results in specific changes in cardiac and pulmonary physiology most notably 1 an increase in the pulmonary vascular resistance PVR through the blood vessels due to their obstruction and 2 a decrease in sur-face area and capillary blood volume for gas exchange through disruption of the normal capillary-alveolar interface with a decrease in the diffusion limit for carbon monoxide DLCO The increase in PVR results in increased afterload on the right heart resulting in right ventricular RV dysfunction and failure Similarly gas exchange abnormalities contribute to decreased ventilatory efficiency and exercise limitation Current treatments which target the prostacyclin endothelin-1 or nitric oxide pathways slow disease progression However these drugs are thought to act largely through vasodilation and not through remodeling For that reason the 5-year survival rate in PAH is still only approximately 60 highlighting the need for therapies targeting pulmonary vascular remodeling pathways
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None