A Randomized Clinical Trial to Evaluate the Effects of Losartan on Cardiovascular Disease in Patients With Mucopolysaccharidoses IV A and VI
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Adverse events related to losartan use
研究概览
简要总结
Mucopolysaccharidoses (MPS) are multisystemic diseases with significant clinical overlap between their types, with cardiac problems being among the most commonly observed manifestations and are also among the main causes of mortality in these patients. For some of the cardiovascular manifestations, such as aortic root dilation and valve diseases, there is no effective treatment currently available. Losartan, on the other hand, has been shown to be an effective drug for dilation of the aortic root, at least in animal models. This study aims to evaluate the safety and efficacy of losartan in patients with MPS VI and other mucopolysaccharidoses.
详细描述
Mucopolysaccharidoses (MPS) are a group of lysosomal diseases characterized by deficiency of enzymes responsible for the degradation of glycosaminoglycans. MPS are multisystemic diseases with significant clinical overlap between their types, with cardiac problems being among the most commonly observed manifestations and are also among the main causes of mortality in these patients. Enzyme replacement therapy and bone marrow transplantation, despite being well established treatments, are not yet capable of reversing or preventing the progression of some of the cardiological manifestations of MPS. On the other hand, these patients may benefit from other conventional drug or surgical treatment, which can be instituted at an appropriate time if there is a better understanding of how these manifestations progress. In particular, the occurrence of aortic root dilation, although described in animal models, has only recently been evaluated in the studies on mucopolysaccharidoses.
In addition, verifying the effectiveness of losartan in controlling these manifestations in the animal model opens the perspective of clinical use of this drug. Losartan is a low-cost drug and, if its efficacy is demonstrated, may represent an accessible therapy directed at the unmet needs of these patients.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 10 Years 至 40 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed biochemical or molecular diagnosis of MPS VI or MPS IVA.
- •Age between 10 and 40 years.
- •Presence of aortic root diameter greater than 1.0 standard deviation, as determined by local measurement.
- •Be in a stable treatment regime in the last 3 months (without performing Enzyme replacement therapy (ERT), or performing ERT on a regular basis).
- •Patient who agree to participate in the study protocol by signing a free informed consent form.
排除标准
- •Patient who underwent previous aortic surgery.
- •Patient with aortic root diameter greater than 5 cm.
- •Patient on angiotensin-converting-enzyme (ACE) inhibitor. In case of use of beta-blocker, or calcium channel blocker, patient without adequate control of blood pressure in the last 3 months.
- •Patients with previous adverse events related to treatment with losartan or contraindication to this treatment.
- •Inability, in the opinion of the investigator, to complete the study procedures.
研究组 & 干预措施
Losartan
Losartan group: 15 patients, both sexes, will receive Losartan 0.4 to 1.4 mg/kg/day orally for 12 months.
干预措施: Losartan (Drug)
Placebo
Placebo group:15 patients, both sexes, will receive oral placebo for 12 months.
干预措施: Placebo (Drug)
结局指标
主要结局
Adverse events related to losartan use
时间窗: 12 months
The frequency of adverse events after 12 months will be compared among the groups
次要结局
- Z score of maximal aortic root diameter measured by Valsalva sinus(12 months)
- Changes of serum levels of transforming growth factor (TGF-Beta-1)(12 months)
- Changes of serum levels of brain-type natriuretic peptide (BNP)(12 months)
- Changes of serum levels of N-terminal pro b-type natriuretic peptide (NT-ProBNP)(12 months)
- Changes of serum levels of creatine kinase-myocardial ban (ck-mb)(12 months)
- Changes of serum levels of Chemokine (C-X-C motif) ligand 6 (CXCL6)(12 months)
- Changes of serum levels of Chemokine (C-X-C motif) ligand 16 (CXCL16)(12 months)
- Changes of serum levels of Endocan-1 (ESM-1)(12 months)
- Changes of serum levels of Placental growth factor (PLGF)(12 months)
- Changes of serum levels of Fatty acid binding protein 3 (FAPB3)(12 months)
- Changes of serum levels of Fatty acid binding protein 4 (FAPB4)(12 months)
- Changes of serum levels of Oncostatin M(12 months)
- Changes of serum levels of Troponin I(12 months)
- Changes of ventricular-vascular coupling measures as assessed by echocardiography between the baseline and 12 months.(12 months)
- Changes in mitral valve regurgitation(12 months)
- Changes in aortic valve regurgitation(12 months)
- Changes in ejection fraction(12 months)
- Changes in left ventricular longitudinal strain(12 months)
- Changes in E/A ratio(12 months)
- Changes in E/e' ratio(12 months)