Systemic Sclerosis (SSc) Vasculopathy: Improved Clinical Monitoring and Treatment
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Flow Mediated Dilatation (FMD)-Diameter of Artery
研究概览
简要总结
Systemic sclerosis (SSc; scleroderma) is a multi-organ systemic disease characterized by activation of immune cells, which results in vascular dysfunction (vasculopathy) and subsequent scarring (fibrosis). SSc has a higher than expect prevalence in the US military. On a national level there are 5,766 SSc patients (ICD-9 710.1) presently cared for in the Veterans Health Administration (VHA). While there is no cure for SSc, studies of therapeutics that can help slow disease progression are valuable to our Veterans. This proposal addresses the solicitation for projects with attention to SSc requested by President Obama after reviewing potential contamination of water at Camp Lejeune. This proposal is a patient-centered outreach for our Veterans with SSc to inform and prevent catastrophic endstage vascular abnormalities, including digital ulcers, pulmonary arterial hypertension (PAH) and scleroderma renal crisis in SSc. The study proposes a novel application of a therapeutic for this disease. A better understanding of the initiating insult and natural progression of SSc vasculopathy is needed in order to develop therapeutics with a goal of curing/treating the underlying disease. This project has the potential to impact not only Veterans with SSc, but also those with vascular abnormalities including digital ulcers, PAH, and renal crisis. This proposal represents a potential major therapeutic advance for our Veterans with SSc.
详细描述
Although SSc is heterogeneous in the extent of organ involvement and prognosis, it is accepted that all SSc cases have a progressive and usually devastating course. Since vasculopathy precedes fibrosis in this disease, a focus on understanding its natural history and preventative measures for vascular dysfunction has profound implications. This pilot work suggests that measurement of endothelial dysfunction with flow mediated dilatation (FMD) holds promise as novel method to assess disease progression as well as the therapeutic efficacy of the pharmacologic compound tetrahydrobiopterin (BH4) in SSc. The investigators believe that BH4, which targets the endothelium, has great promise to reduce SSc-related tissue hypoxia, end organ damage, and potentially may impact underlying disease progression. The first aim will adopt an integrative approach and validate a novel, non-invasive technique, FMD to define vasculopathy in SSc. The second aim and third aim (which is reported in this PRS report) will examine if BH4 is effective in ameliorating vascular dysfunction in patients with SSc and determine the role of oxidative stress in BH4-mediated improvements in vascular function in patients with SSc. The overarching goal of these aims is to improve vasculopathy detection and management in Veterans with SSc.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Drug was dispensed by the investigational drug services. A controlled, counter-balanced, double-blind, crossover experimental design with two conditions, BH4 and placebo, was employed. There was a washout period of at least 5 days before crossing over into the alternate condition. On
入排标准
- 年龄范围
- 18 Years 至 95 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Diagnosis of systemic sclerosis (SSc, scleroderma) by ACR/EULAR 2013 criteria.
排除标准
- •Age < 18
- •Pregnant or breast feeding
- •Unwillingness to consent
研究组 & 干预措施
Placebo before BH4
Six SSc received oral placebo 10 mg/kg and had flow mediated dilatation measured. After a five day washout they crossed over to oral BH4 10 mg/kg and had flow mediated dilatation measured. Blood samples were obtained from these SSc patients and assessed for oxidative stress.
干预措施: BH4 (Drug)
Placebo before BH4
Six SSc received oral placebo 10 mg/kg and had flow mediated dilatation measured. After a five day washout they crossed over to oral BH4 10 mg/kg and had flow mediated dilatation measured. Blood samples were obtained from these SSc patients and assessed for oxidative stress.
干预措施: Vasculopathy assessment (Diagnostic Test)
Placebo before BH4
Six SSc received oral placebo 10 mg/kg and had flow mediated dilatation measured. After a five day washout they crossed over to oral BH4 10 mg/kg and had flow mediated dilatation measured. Blood samples were obtained from these SSc patients and assessed for oxidative stress.
干预措施: Placebo (Drug)
BH4 before Placebo
Six SSc received oral BH4 10 mg/kg and had flow mediated dilatation measured. After a five day washout they crossed over to oral placebo 10 mg/kg and had flow mediated dilatation measured. Blood samples were obtained from these SSc patients and assessed for oxidative stress.
干预措施: BH4 (Drug)
BH4 before Placebo
Six SSc received oral BH4 10 mg/kg and had flow mediated dilatation measured. After a five day washout they crossed over to oral placebo 10 mg/kg and had flow mediated dilatation measured. Blood samples were obtained from these SSc patients and assessed for oxidative stress.
干预措施: Vasculopathy assessment (Diagnostic Test)
BH4 before Placebo
Six SSc received oral BH4 10 mg/kg and had flow mediated dilatation measured. After a five day washout they crossed over to oral placebo 10 mg/kg and had flow mediated dilatation measured. Blood samples were obtained from these SSc patients and assessed for oxidative stress.
干预措施: Placebo (Drug)
结局指标
主要结局
Flow Mediated Dilatation (FMD)-Diameter of Artery
时间窗: FMD was obtained on a single day at two different time points (after placebo and intervention) after a 5 day washout period.
FMD diameter of artery (mm, higher better)
Flow Mediated Dilatation-shear Rate
时间窗: FMD was obtained on a single day at two different time points (after placebo and intervention) after a 5 day wash out period.
Flow Mediated Dilatation- Blood Velocity
时间窗: FMD was obtained on a single day at two different time points (after placebo and intervention) after a 5 day wash out period.
Flow Mediated Dilatation-blood Flow
时间窗: FMD was obtained on a single day at two different time points (after placebo and intervention) after a 5 day wash out period.
次要结局
- Oxidative Stress Measurement- Ferric Reducing Ability of Plasma (FRAP)(Oxidative stress measurements were obtained on a single day at two different time points (after placebo and intervention) after a 5-day wash out period.)
- Oxidative Stress Measurement- Superoxide Dismutase (SOD)(Oxidative stress measurements were obtained on a single day at two different time points (after placebo and intervention) after a 5-day wash out period.)
- Oxidative Stress Measurement- Interleukin 6 (IL-6)(Oxidative stress measurements were obtained on a single day at two different time points (after placebo and intervention) after a 5-day wash out period.)
- Oxidative Stress Measurement- Tumor Necrosis Factor Alpha (TNF-α,(Oxidative stress measurements were obtained on a single day at two different time points (after placebo and intervention) after a 5-day wash out period.)
- Oxidative Stress Measurement- C-reactive Protein (CRP)(Oxidative stress measurements were obtained on a single day at two different time points (after placebo and intervention) after a 5-day wash out period.)
- Oxidative Stress Measurement-MDA: Malondialdehyde(Oxidative stress measurements were obtained on a single day at two different time points (after placebo and intervention) after a 5-day wash out period.)
- Oxidative Stress Measurement-catalase (CAT)(Oxidative stress measurements were obtained on a single day at two different time points (after placebo and intervention) after a 5-day wash out period.)
- Oxidative Stress Measurement- Protein Carbonyl(Oxidative stress measurements were obtained on a single day at two different time points (after placebo and intervention) after a 5-day wash out period.)