Ignite Creation Date:
2024-05-06 @ 6:44 PM
Last Modification Date:
2024-10-26 @ 2:53 PM
Study NCT ID:
NCT05767918
Status:
COMPLETED
Last Update Posted:
2023-03-14
First Post:
2023-03-02
Brief Title:
StratosPHere Non-interventional Study
Sponsor:
Papworth Hospital NHS Foundation Trust
Organization:
Papworth Hospital NHS Foundation Trust
Study Overview
Official Title:
StratosPHere Optimal Biomarkers to Ascertain Target Engagement in Therapies Targeting the BMPR2 Pathway in Pulmonary Arterial Hypertension PAH
Status:
COMPLETED
Status Verified Date:
2023-03
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:
None
Brief Summary:
Pulmonary Arterial Hypertension is a progressive disease that has no cure Patients die young and are limited in their daily activity Current treatments only treat the symptoms of the disease rather than the underlying cause At least 1 in 5 patients has a change in a gene called the bone morphogenetic type 2 protein or BMPR2 Extensive evidence supports the concept of addressing the reduced levels of the BMPR2 protein to reverse disease Through work already undertaken by this group two potential therapies which increase BMPR2 have been identified for use in a future randomised control trial In order for a clinical trial to be informative we need an accurate way of measuring the protein or the effects of the protein known as a biomarker This study will use blood samples taken from 17 patients and 30 healthy participants over various time-points 2-5 visits over 5 weeks for healthy controls 2 visits approximately four months apart for patients Laboratory work will help identify the best biomarkers for subsequent therapy studies By defining the best biomarkers we can speed up the drug development in this rare disease
Detailed Description:
Pulmonary arterial hypertension PAH is a devastating and life-threatening disease that is associated with high morbidity and mortality The disease is characterised by increased pulmonary arterial pressure the blood pressure of the arteries found in the lungs This increase in pressure is due to the progressive narrowing and obliteration of these blood vessels often leading in failure of the right ventricle of the heart
Current treatments for PAH utilise vasodilators to lessen the effects of the narrowing of the blood vessels and reduce blood pressure However a major breakthrough in our understanding of the molecular basis of PAH has been the identification of mutations or changes in important genes involved in the normal function of the lung vasculature Mutations in the gene encoding bone morphogenetic protein type II receptor BMPR2 have to date been the most important genetic mutation identified present in the majority 75 of heritable PAH cases and approximately 11-44 of idiopathic cases Dunmore et al Such mutations result in a significantly reduced amount of this receptor on key cells in the pulmonary vasculature the result of which is disruption of the normal cellular events and the subsequent development of vascular disease Extensive research now exists on the role of BMPR2 in the development of PAH and pre-clinical findings support the targeting of BMPR2 as a potential treatment however there are currently no therapeutics targeting the receptor in development
To define the optimal biological biomarker end point of BMPR2 target engagement we will assess two study populations over a longitudinal time-course using peripheral blood samples
Samples will be taken from a patient population with idiopathic or hereditary pulmonary arterial hypertension n17 and healthy volunteers n30 who will act as a control group
Recruitment of healthy volunteers will be targeted at female aged 30-40 years as this is in line with the demographics of a typical PAH patient cohort Blood samples will be collected from the control group across a total of 6 time points the first 5 samples will be offered on a weekly basis with a final blood sample taken at 4 months Sampling on weeks 2 3 4 and 16 will be optional The expected duration for healthy volunteers is a total of 5 weeks with no follow up
PAH participants will be sampled during routine clinic reviews over a four-month time period Sampling will occur at separate two distinct time-points three to six months apart IPAHHPAH participants will be recruited based upon their diagnosis and will be in WHO functional class I-IV and on stable medication or have unchanged PAH for at least one month prior to screening The total duration for participants in this group will be approximately 3-6 months typically 4 months dependent on scheduling of clinical visits
This will provide critical information for a future RCT testing two novel therapies with the potential to improve survival and quality of life for people diagnosed with PAH by providing a personalised approach to treatment
Current treatments for PAH utilise vasodilators to lessen the effects of the narrowing of the blood vessels and reduce blood pressure However a major breakthrough in our understanding of the molecular basis of PAH has been the identification of mutations or changes in important genes involved in the normal function of the lung vasculature Mutations in the gene encoding bone morphogenetic protein type II receptor BMPR2 have to date been the most important genetic mutation identified present in the majority 75 of heritable PAH cases and approximately 11-44 of idiopathic cases Dunmore et al Such mutations result in a significantly reduced amount of this receptor on key cells in the pulmonary vasculature the result of which is disruption of the normal cellular events and the subsequent development of vascular disease Extensive research now exists on the role of BMPR2 in the development of PAH and pre-clinical findings support the targeting of BMPR2 as a potential treatment however there are currently no therapeutics targeting the receptor in development
To define the optimal biological biomarker end point of BMPR2 target engagement we will assess two study populations over a longitudinal time-course using peripheral blood samples
Samples will be taken from a patient population with idiopathic or hereditary pulmonary arterial hypertension n17 and healthy volunteers n30 who will act as a control group
Recruitment of healthy volunteers will be targeted at female aged 30-40 years as this is in line with the demographics of a typical PAH patient cohort Blood samples will be collected from the control group across a total of 6 time points the first 5 samples will be offered on a weekly basis with a final blood sample taken at 4 months Sampling on weeks 2 3 4 and 16 will be optional The expected duration for healthy volunteers is a total of 5 weeks with no follow up
PAH participants will be sampled during routine clinic reviews over a four-month time period Sampling will occur at separate two distinct time-points three to six months apart IPAHHPAH participants will be recruited based upon their diagnosis and will be in WHO functional class I-IV and on stable medication or have unchanged PAH for at least one month prior to screening The total duration for participants in this group will be approximately 3-6 months typically 4 months dependent on scheduling of clinical visits
This will provide critical information for a future RCT testing two novel therapies with the potential to improve survival and quality of life for people diagnosed with PAH by providing a personalised approach to treatment
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
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