Evaluation of Losartan on Cardiovascular Disease in Patients With Mucopolysaccharidoses IV A and VI

NCT ID: NCT03632213

Last Updated: 2022-12-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-07
• Study Completion Date: 2023-08-03

Brief Summary

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.

Detailed Description

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.

Conditions

Mucopolysaccharidosis IV A; Mucopolysaccharidosis VI; Mucopolysaccharidoses; MPS IV A; MPS VI; MPS - Mucopolysaccharidosis; Morquio A Syndrome; Morquio Syndrome A; Morquio Syndrome

Keywords

Mucopolysaccharidoses; Losartan; Aortic root dilatation; Echocardiogram; MPS IV; MPS VI

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Losartan

Losartan group: 15 patients, both sexes, will receive Losartan 0.4 to 1.4 mg/kg/day orally for 12 months.

Group Type: ACTIVE_COMPARATOR

Losartan

Intervention Type: DRUG

Losartan group: 15 patients, both sexes, will receive Losartan 0.4 to 1.4 mg/kg/day orally for 12 months.

Placebo

Placebo group:15 patients, both sexes, will receive oral placebo for 12 months.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo group: 15 patients, both sexes, will receive oral placebo for 12 months.

Interventions

Losartan

Losartan group: 15 patients, both sexes, will receive Losartan 0.4 to 1.4 mg/kg/day orally for 12 months.

Intervention Type: DRUG

Placebo

Placebo group: 15 patients, both sexes, will receive oral placebo for 12 months.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Isaac Foundation

UNKNOWN

Sponsor Role: collaborator

Hospital de Clinicas de Porto Alegre

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Roberto Giugliani, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital de Clinicas de Porto Alegre

Guilherme Baldo, PhD

Role: STUDY_DIRECTOR

Hospital de Clinicas de Porto Algre

Locations

Hospital de Clinicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Countries

Brazil

Other Identifiers

17-0685

Identifier Type: -

Identifier Source: org_study_id