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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
10
Hospital de Clinicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, Brazil
Adverse events related to losartan use
The frequency of adverse events after 12 months will be compared among the groups
Time frame: 12 months
Z score of maximal aortic root diameter measured by Valsalva sinus
Reduction over time in the Z score of maximal aortic root diameter measured by Valsalva sinus echocardiogram between the baseline assessment and 12 months after treatment with losartan.
Time frame: 12 months
Changes of serum levels of transforming growth factor (TGF-Beta-1)
Changes of serum levels of transforming growth factor (TGF-Beta-1) between baseline and 12 months
Time frame: 12 months
Changes of serum levels of brain-type natriuretic peptide (BNP)
Changes of serum levels of brain-type natriuretic peptide between baseline and 12 months
Time frame: 12 months
Changes of serum levels of N-terminal pro b-type natriuretic peptide (NT-ProBNP)
Changes of serum levels of N-terminal pro b-type natriuretic (NT-ProBNP) peptide between baseline and 12 months
Time frame: 12 months
Changes of serum levels of creatine kinase-myocardial ban (ck-mb)
Changes of serum levels of creatine kinase-myocardial ban (ck-mb) between baseline and 12 months
Time frame: 12 months
Changes of serum levels of Chemokine (C-X-C motif) ligand 6 (CXCL6)
Changes of serum levels of Chemokine (C-X-C motif) ligand 6 (CXCL6) between baseline and 12 months
Time frame: 12 months
Changes of serum levels of Chemokine (C-X-C motif) ligand 16 (CXCL16)
Changes of serum levels of Chemokine (C-X-C motif) ligand 16 (CXCL16) between baseline and 12 months
Time frame: 12 months
Changes of serum levels of Endocan-1 (ESM-1)
Changes of serum levels of Endocan-1 (ESM-1) between baseline and 12 months
Time frame: 12 months
Changes of serum levels of Placental growth factor (PLGF)
Changes of serum levels ofPlacental growth factor (PLGF) between baseline and 12 months
Time frame: 12 months
Changes of serum levels of Fatty acid binding protein 3 (FAPB3)
Changes of serum levels of Fatty acid binding protein 3 (FAPB3) between baseline and 12 months
Time frame: 12 months
Changes of serum levels of Fatty acid binding protein 4 (FAPB4)
Changes of serum levels of Fatty acid binding protein 4 (FAPB4) between baseline and 12 months
Time frame: 12 months
Changes of serum levels of Oncostatin M
Changes of serum levels of Oncostatin M between baseline and 12 months
Time frame: 12 months
Changes of serum levels of Troponin I
Changes of serum levels of Troponin I between baseline and 12 months
Time frame: 12 months
Changes of ventricular-vascular coupling measures as assessed by echocardiography between the baseline and 12 months.
Reduction over time in the ventricular-vascular coupling measures as assessed by echocardiography between the baseline and 12 months.
Time frame: 12 months
Changes in mitral valve regurgitation
Alteration of the parameter of mitral valve regurgitation as assessed by a semi-quantitative echocardiographic method between the baseline and 12 months.
Time frame: 12 months
Changes in aortic valve regurgitation
Alteration of the parameter of aortic valve regurgitation as assessed by a semi-quantitative echocardiographic method between the baseline and 12 months.
Time frame: 12 months
Changes in ejection fraction
Alteration of the ejection fraction measurement as assessed by echocardiography between the baseline and 12 months.
Time frame: 12 months
Changes in left ventricular longitudinal strain
Alteration of the measurement of left ventricular longitudinal strain as assessed by echocardiography between the baseline and 12 months.
Time frame: 12 months
Changes in E/A ratio
Alteration of the parameter E/A ratio as assessed by echocardiography between the baseline and 12 months .
Time frame: 12 months
Changes in E/e' ratio
Alteration of the parameter E/e' ratio as assessed by echocardiography between the baseline and 12 months.
Time frame: 12 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.