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

NCT03632213 | Unknown Phase 2

• 1 other identifier: 17-0685
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Adverse events related to losartan use

  The frequency of adverse events after 12 months will be compared among the groups

  12 months

Secondary Outcomes (20)

• 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

Other Outcomes (2)

• Glycosaminoglycan after 6 months

  6 months

• Glycosaminoglycan after 12 months

  12 months

Study Arms (2)

Losartan

ACTIVE COMPARATOR

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

Drug: Losartan

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Losartan DRUG

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

Losartan

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 10 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hospital de Clinicas de Porto Alegre: lead
• The Isaac Foundation: collaborator

Study Sites (1)

Hospital de Clinicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

MeSH Terms

Conditions

Mucopolysaccharidosis IV; Mucopolysaccharidosis VI; Mucopolysaccharidoses

Interventions

Losartan

Condition Hierarchy (Ancestors)

Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Study Officials

• Roberto Giugliani, MD, PhD

  Hospital de Clinicas de Porto Alegre

  PRINCIPAL INVESTIGATOR

• Guilherme Baldo, PhD

  Hospital de Clinicas de Porto Algre

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Experimental group: 15 patients, both sexes, will receive Losartan 25 mg orally for 12 months. Control group: 15 patients, both sexes, will receive oral placebo for 12 months. Eligible research participants for treatment will be randomly assigned to a treatment group or a control group in a ratio of 1: 1. The groups will be stratified by age and type of MPS in the following strata: A) Diagnosis of MPS IVA: 20 patients expected B) Diagnosis of MPS VI: 10 patients expected

Study Record Dates

• First Submitted: August 3, 2018
• First Posted: August 15, 2018
• Study Start: November 7, 2018
• Primary Completion: May 4, 2023
• Study Completion: August 3, 2023
• Last Updated: December 19, 2022

Record last verified: 2022-12

Locations

BR (1)