PET Assessment of Disease Activity and Cardiovascular Disease Risk in ANCA-associated Vasculitis
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Change in tracer ([18F]-FDG, [68Ga]-DOTATATE, and [68Ga]-FAPI) uptake (calculated using maximum standardised uptake values (SUVmax)) within regions of interest between baseline and remission)
研究概览
简要总结
Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a severe autoimmune condition characterised by inflammation of small blood vessels. The condition causes multi-organ dysfunction and, if left untreated, is usually fatal. AAV is difficult to diagnose and the degree of disease activity is challenging to monitor. Current methods of disease activity assessment are either inaccurate (blood tests), invasive (biopsy), or non-specific (imaging). Additionally, though modern treatments are effective, patients with AAV remain at a substantially increased risk of cardiovascular disease (CVD) in the long-term. There is therefore an urgent need for a tool which is able to reliably identify disease, and assess long-term CVD risk.
Total-Body PET imaging with FDG, DOTATATE, and FAPI radiotracers may provide the answer. This study will recruit patients with active AAV, together with a control group of individuals without the disease, to undergo Total-Body FDG, DOTATATE, and FAPI PET scanning and compare the results with established measures of disease activity and CVD risk assessment.
The investigators believe that Total-Body PET scanning will be capable of accurately identifying AAV disease and those at increased CVD risk. This could enhance understanding and improve the management of those with the condition.
This study will recruit a group of patients with AAV and a comparator groups of 'matched' individuals without AAV. Comparisons between groups will allow the investigators to ensure that the changes seen are due to AAV disease. The study will recruit a minimum of 30 and a maximum of 90 participants in the AAV group, and a minimum of 10 and maximum of 30 participants in the matched control group.
AAV subjects and matched control subjects will undergo baseline total-body PET scanning with either one, two or three radiotracers ([18F]-FDG, [68Ga]-DOTATATE, and [68Ga]-FAPI). Alongside this they will receive assessment of cardiovascular disease risk including 24-hour blood pressure measurement, arterial stiffness measurement, and retinal scanning. Participants will also supply a blood and urine sample.
For matched control subjects, their participation will end at this point. Subjects in the AAV group will undergo repeat assessment with total-body PET imaging and cardiovascular disease risk measurement once their condition is in remission (usually after around 3-6 months).
The investigators will compare PET scan results between groups, and with cardiovascular assessments. This will allow determination of whether total-body PET scanning can identify AAV disease activity, and whether it can inform CVD risk.
All research activity will be carried out within the University of Edinburgh BioQuarter, including the Royal infirmary of Edinburgh, the Edinburgh Imaging Facility, and Queen's Medical Research Institute.
详细描述
Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a rare condition which causes widespread blood vessel inflammation, leading to dysfunction in several organs. The condition is autoimmune, meaning that it is driven by an abnormal response from the body's own immune system, though the exact cause is unknown. Without treatment most patients with AAV will die. However current treatment is effective, with ~90% of patients alive at 1-year following diagnosis. Once the initial phase of the disease is controlled, patients remain at risk of relapse which can be difficult to detect. Additionally, in the long term, patients remain at an increased risk of death as a result of cardiovascular disease (CVD), including heart attacks and strokes.
The diagnosis of AAV is challenging and often delayed, meaning established organ damage is often present at diagnosis. Accurate assessment of disease activity is essential to guide best treatment in AAV. Smouldering, unchecked inflammation contributes to morbidity and to the development of CVD. Conversely, attributing symptoms to active disease when they are due to established injury risks overtreatment and associated side effects, which can be significant.
Current methods of disease activity assessment are limited. Biopsy is considered the gold standard, however, can only assess disease in one organ at a time, and is an invasive and unpleasant test. Several scans are currently available, though each is also limited in terms of coverage and accuracy. Accordingly, new methods of disease activity assessment are required which provide an accurate, non-invasive, and multi-system approach, both at presentation and throughout the disease course.
Additionally, even when disease control is optimum, patients with AAV remain at an increased risk of CVD. Methods to identify those at the highest risk of CVD events are lacking, thus personalising preventative therapies remains a challenge. Tools that can highlight those at an increased risk of CVD events are urgently needed.
Total-Body positron emission tomography (PET) scanning provides a potential solution to both of these problems.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 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
- 是
入选标准
- •18+ years of age
- •Diagnosis of active AAV (AAV group)
排除标准
- •Outwith early treatment window (must receive baseline scan <3 weeks from starting treatment)
- •Pregnancy or breastfeeding
- •Advanced renal dysfunction (eGFR <15ml/min/1.73m2)
- •Adverse reaction or hypersensitivity to proposed radiotracers
- •Insulin-dependent diabetes mellitus
- •Patients without mental capacity or willingness to provide informed consent
研究组 & 干预措施
ANCA associated vasculitis (AAV) group
All participants will have a diagnosis of ANCA-associated vasculitis (AAV) in accordance with the 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides criteria and clinician's assessment. At enrolment, participants in the AAV group will have active disease, as defined by the presence of symptoms and signs attributable to active vasculitis necessitating the commencement or increase in immunosuppressive treatment other than glucocorticoids.
In order to return for the follow-up visit, participants will be in clinical remission. Remission will be defined as Birmingham Vasculitis Activity Score (BVAS) = 0 for at least two months whilst taking prednisolone at a daily of dose ≤7.5mg in conjunction with the treating clinician's assessment of clinically silent disease.
Matched control group
All participants will be matched with the AAV group based on age, gender, ethnicity, and cardiovascular disease risk factors including impaired kidney function. They will have no additional health problems and be taking no additional medications (other than those relevant to cardiovascular disease risk) that may interfere with PET imaging.
结局指标
主要结局
Change in tracer ([18F]-FDG, [68Ga]-DOTATATE, and [68Ga]-FAPI) uptake (calculated using maximum standardised uptake values (SUVmax)) within regions of interest between baseline and remission)
时间窗: 3-12 months
The change in PET radiotracer uptake within regions of interest between patients with active AAV (e.g. at baseline) and patients in remission (e.g. at follow-up)
次要结局
- Correlation between tracer uptake (SUVmax and SUVmean) and established surrogate measures of CVD risk including: o Arterial stiffness o 24-hour ambulatory blood pressure o Retinal OCT imaging metrics(3-12 months)
- Correlation between tracer uptake (SUVmax and SUVmean) and established measures of disease activity including: o CRP o ANCA titre o Patient reported disease activity o Physician estimated disease activity(3-12 months)