A Double-blinded, Placebo-controlled Pilot Study of Dimethyl Fumarate (DMF) in Pulmonary Arterial Hypertension (PAH) Associated With Systemic Sclerosis (SSc-PAH): The Effect of DMF on Clinical Disease and Biomarkers of Oxidative Stress.
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 6
- 试验地点
- 4
- 主要终点
- 6 Minute Walk Distance (6MWD)
研究概览
简要总结
A double-blinded, placebo-controlled study of Dimethyl fumarate (DMF) in 34 Systemic Sclerosis-Pulmonary Hypertension (SSc-PAH) patients. The study will determine safety and the primary outcome variability for DMF in treating SSc-PAH; the primary outcome of clinical efficacy in this pilot trial will be improvement in 6-minute walk distance (6MWD).
详细描述
A double-blinded, placebo-controlled study of Dimethyl fumarate (DMF) in 34 Systemic Sclerosis-Pulmonary Hypertension (SSc-PAH) patients. The study medication will be added to stable background PAH medication(s). Subjects will be dosed for 24 weeks, will undergo examination every 8 weeks, and will be finally evaluated 12 weeks after completion of treatment. Dosage will begin at once daily oral doses of 120mg for the first 7 days and follow the up-titration schedule to a maintenance dose of 240mg twice a day (or highest tolerated dose of a minimum of 120mg twice a day by the start of Week 8) for the remainder of the study. Participation will be for a total of 40 weeks, including a 4-week screening period, 24 weeks of drug, and a safety follow-up 12 weeks after the last dose. The study will determine the safety and the primary outcome variability for DMF in treating SSc-PAH; the primary outcome of clinical efficacy in this pilot trial will be improvement in 6-minute walk distance (6MWD).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed inform consent prior to any study-mandated procedures
- •Adult patients 18-80 years of age
- •World Health Organization Group 1 PAH associated with scleroderma (SSc-PAH)
- •WHO functional Class II-III
- •6MWD 150 to 450 meters
- •Right heart catheterization demonstrating mPAP≥ 25 mmHg and PCWP or left ventricular end diastolic pressure ≤15mm Hg and pulmonary vascular resistance ≥240 dynes/cm-5 (3 Wood units) within 12 weeks prior to study entry.
- •ACR defined systemic sclerosis
排除标准
- •Pulmonary hypertension associated with
- •PAH of any etiology other than scleroderma
- •PH of any etiology other than WHO Group I PAH
- •Pulmonary venous hypertension defined as PCWP or LVEDP >15 mHg
- •Untreated sleep apnea with AHI >20 or SaO2 Nadir <87%
- •Chronic thromboembolic disease
- •Sarcoidosis
- •Participation in a clinical investigational study within the previous 30 days
- •Moderate to severe hepatic impairment (e.g., Child-Pugh Class B or C)
- •Renal failure defined as:
- •estimated creatinine clearance <30 m/min
- •serum creatinine>2.5 mg/dl
- •Serum aspartate aminotransferase (AST) and or alanine aminotransferase (ALT) > 1.5 times the upper limit of normal
- •Systolic blood pressure < 90mmHg
- •Recently started (< 8 weeks prior to randomization) or planned cardiopulmonary rehabilitation program based on exercise
- •Pregnant or lactating women
- •Need for HAART therapy
- •Planned treatment or treatment with another investigational drug within 1 month prior to start
- •Moderate to severe interstitial lung disease, defined by FVC < 80% or evidence on HRCT of fibrosis or ground glass changes involving more than 30% of lung parenchyma
研究组 & 干预措施
Placebo
Twice daily oral doses of placebo for 12 weeks
干预措施: Placebo Oral Tablet (Drug)
Dimethyl Fumarate (DMF)
Twice daily oral doses of Dimethyl Fumarate (DMF) 120mg for the first 7 days followed by the maintenance dose of Dimethyl Fumarate (DMF) 240mg twice a day. Subjects will be dosed for 24 weeks
干预措施: Dimethyl Fumarate (DMF) (Drug)
结局指标
主要结局
6 Minute Walk Distance (6MWD)
时间窗: Baseline to Week 24
The primary outcome of clinical efficacy in this study is improvement in 6-minute walk distance (6MWD). Data depict the mean change (%) at end-of-study-treatment (Week 24) from baseline in both treatment groups, utilizing the Last Observation Carried Forward of withdrawn subjects.
次要结局
- Serum Markers of Oxidative Stress(Baseline to Week 24)
- Proteomic Biomarkers(Baseline to Week 24)
- Clinical Worsening(Baseline to Week 24)
- Borg Dyspnea Index (BDI)(Baseline to Week 24)
研究者
Robert Lafyatis
Professor of Medicine and the Thomas Medsger Professor in Arthritis Research
University of Pittsburgh