Nailfold Capillaroscopy in PH: Are Nailfold Changes Reversible With Pulmonary Vasodilator Therapy?
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Linear Capillary Density
研究概览
简要总结
Pulmonary hypertension (PH) is an uncommon condition and can often be difficult to diagnose. It means elevated blood pressure in the lungs which can rapidly lead to failure of the right side of the heart and is ultimately fatal. Diagnosing PH currently involves a number of scans, breathing tests and often an invasive test called right heart catheterisation [RHC] (which involves inserting a tube into a large vein to measure the lung blood pressure from the).
The investigators propose using a scan of the nailbeds called "Nailfold (Video) Capillaroscopy" to see whether this measurements correspond to the pressures that the investigators measure at the time of RHC and whether these measures change with treatment for PH.
The investigators wish to answer the hypotheses that:
- The measurements of the nailbed blood vessels are correlated with the invasive right heart catheter values across all groups of PH
- The abnormalities seen in systemic sclerosis are reversible with treatment with pulmonary vasodilator drugs
- This change will be significantly more than any change seen in other types of pulmonary hypertension with these drugs
- Changes in the nailbed blood vessels with treatment will reflect changes in the usual parameters used to measure treatment response in PH:
The scan uses a camera microscope connected to a laptop, does not involve radiation and can be completed within 30 minutes. The results are sent to the University of Manchester where they are analysed by computer software.
If patients are found to have pulmonary hypertension and are started on medication (pulmonary vasodilators) to open up the blood vessels of the lungs, the investigators will then repeat the scan at this point. The investigators will compare the results between different forms of PH before and after treatment.
详细描述
Pulmonary arterial hypertension (PAH) is a cause of precapillary pulmonary hypertension haemodynamically, where the disease process is caused by progressive narrowing of the arterioles of the pulmonary circuit. PH puts the right side of the heart under increasing strain, which causes it to fail and is ultimately fatal. PAH occurs in about 15% of patients with systemic sclerosis (SSc) and approximately 25% of cases of PAH in our centre are caused by SSc (SSc-PAH). It is the second leading cause of disease related death in SSc accounting for 26% of these deaths1.
Abnormalities of the small blood vessels are one of the main "drivers" of SSc. The poor blood supply/lack of oxygen interacts with fibrosis (scarring: overproduction of collagen) and causes damage to numerous organs (resulting for example in finger ulcers, skin thickening, kidney injury, lung fibrosis and gastro-intestinal involvement in addition to PAH).
It has been clearly established that these abnormalities are detectable in the nailbeds in SSc and form part of the diagnostic criteria for the disease 2,3. Moreover there is data that these abnormalities seem to correlate with disease severity in SSc, including with presence and severity of PAH 4.
There is limited evidence that blood vessel abnormalities in tissues outside of the lungs also occur in patients with so-called 'Idiopathic' Pulmonary Arterial Hypertension (IPAH), the other major cause of PAH and in chronic thromboembolic pulmonary hypertension (CTEPH) a disease where PH is caused by scarring from previous blood clots5 . However the blood vessel abnormalities described are more subtle than in SSc-PAH. It is not clear if they are related to issues with the pumping of the heart rather than an inherent issue with blood vessels outside of the lungs. It is not currently known if similar abnormalities exist in other forms of PH including PH related to lung disease (group 3 PH). Despite differences in the underlying pathology, all of these forms of PH are treated with drugs that open the vessels of the lungs (pulmonary vasodilators).
Our project aims to understand how patients with different forms of PH respond to pulmonary vasodilator therapy and how this differs between different types of pulmonary hypertension. The investigators intend to use the technique of nailfold capillaroscopy (examination of the smallest blood vessels - capillaries - of the nail bed with a microscope) to look at patients with different types of PH before and after treatment (or before and after treatment intensification).
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •For inpatient enrolment:
- •Suspected diagnosis of group 1,3 or 4 pulmonary hypertension undergoing inpatient assessment at nationally designated centre
- •Age > 18 years
- •For follow up scanning of those enrolled as an inpatient:
- •Confirmed diagnosis of pulmonary hypertension assessed at nationally designated centre fulfilling criteria for group 1, 3 or 4 disease
- •Commencing PH targeted therapy, specifically one or more of: a phosphodiesterase 5 inhibitor (PDE5i), an ET receptor antagonist (ERA), parenteral prostanoid therapy, selexipag, riociguat, sotatercept.
- •For outpatient enrolment
- •Confirmed diagnosis of pulmonary hypertension assessed at nationally designated centre fulfilling criteria for group 1, 3 or 4 disease
- •Age > 18 years
- •Escalating PH targeted therapy, specifically one or more of: a phosphodiesterase 5 inhibitor (PDE5i), an ET receptor antagonist (ERA), parenteral prostanoid therapy, selexipag, riociguat, sotatercept.
- •Target of > 25% of patients recruited at diagnosis and to have an SSc-spectrum disorder fulfilling either ACR/EULAR 2013 or VEDOSS (very early diagnosis of SSc) criteria.
- •Target of > 25% of patients recruited at diagnosis and to have non-SSc group 1 (PAH) diagnosis (as determined by national MDT decision).
排除标准
- •Patients with confirmed group 2 or group 5 pulmonary hypertension
- •Patients < 18 years of age
- •Patients unable to participate in nailbed microscopy (through e.g. amputation, severe contractures or other musculoskeletal issues).
- •(From follow up) Patients not being commenced on pulmonary vasodilator therapy at the point of diagnosis.
- •Patients already on maximal PH therapy
- •Patients lacking capacity to consent to participation
- •Patients who are non-fluent English speakers, where suitable translation cannot be found within a time frame that makes the study feasible.
- •Patients with a life expectancy < 4 months
- •Patients who have consumed nicotine or caffeine within the last 4 - 6 hours
- •Patients wearing nail polish / varnish/ extensions that preclude adequate nailbed visualisation.
研究组 & 干预措施
SSc-PAH at diagnosis
Recruited at diagnosis with SSc-spectrum disorder fulfilling either ACR/EULAR 2013 or VEDOSS (very early diagnosis of SSc) criteria.
干预措施: Standard of Care therapy (Drug)
SSc-PAH at follow up
SSc-PAH patient undergoing treatment intensification in clinic. SSc-spectrum disorder fulfilling either ACR/EULAR 2013 or VEDOSS (very early diagnosis of SSc) criteria
干预措施: Standard of Care therapy (Drug)
Non-SSc Group 1 PAH at diagnosis
Patients with Group 1 PAH other than SSc, as determined by National MDT decision recruited at the point of diagnosis
干预措施: Standard of Care therapy (Drug)
Non-SSc Group 1 PAH at follow up
Patients with Group 1 PAH other than SSc, as determined by National MDT decision recruited at the point of intensification of therapy in clinic
干预措施: Standard of Care therapy (Drug)
Group 3 PH at diagnosis
Patients with group 3 PH (made by national MDT decision) recruited at the point of diagnosis
干预措施: Standard of Care therapy (Drug)
Group 4 PH at diagnosis
Patients with group 4 PH (made by national MDT decision), recruited at the point of diagnosis
干预措施: Standard of Care therapy (Drug)
结局指标
主要结局
Linear Capillary Density
时间窗: 4 - 6 months into therapy
Change in Linear Capillary Density over time on Pulmonary Vasodilator Therapy (in capillary loops/mm)
次要结局
- NVC Capillary Diameter(Baseline and first follow up visit (4-6 months))
- Angular dispersion index(Baseline and first follow up visit (4-6 months))
- Overall capillaroscopic pattern(Baseline and first follow up visit (4-6 months))
- Pulmonary Vascular Resistance(Baseline only)
- Mean Pulmonary Arterial Pressure, Pulmonary Artery Systolic Pressure, Right Atrial Pressure(Baseline only)
- Mixed venous saturation(Baseline Only)
- Stroke Volume Index(Baseline only)
- Cardiac Index(Baseline only)
- Right and Left Ventricular Ejection Fraction(Baseline only)
- Tricuspid Regurgitant Jet Velocity(Baseline only)
- Tricuspid Regurgitant Pulmonary Gradient(Baseline only)
- Tricuspid Annular Plane Systolic Excursion(Baseline only)
- Right atrial area(Baseline only)
- Tricuspid Annular Plane Systolic Excursion: systolic pulmonary artery pressure ratio(Baseline Only)
- Right ventricular end systolic volume index(Baseline only)
- WHO Functional Class(Baseline and first follow up visit (4-6 months))
- 6 minute walk test/distance(Baseline and first follow up visit (4-6 months))
- NT-proBNP(Baseline and first follow up visit (4-6 months))
- Emphasis-10 score(Baseline and first follow up visit (4-6 months))
- DLCO(Baseline only)
- Compera 2.0 Risk status(Baseline and first follow up visit (4-6 months))
- Raynaud's condition score(Baseline and first follow up visit (4-6 months))
研究者
William Kerrigan
PhD Student
University of Glasgow