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Mucopolysaccharidosis IV APhase 2NCT03632213

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

A Phase 2 study testing Losartan in people with Mucopolysaccharidosis IV A and Mucopolysaccharidosis VI, run by Hospital de Clinicas de Porto Alegre at 1 site in Brazil.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 10 to 40 years
What is being tested?
Losartan
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
10 participants
Where
1 siteBrazil
Study dates
7 Nov 2018to 3 Aug 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 10 to 40 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

Brazil1 site

  • Hospital de Clinicas de Porto Alegre

    Porto Alegre, Rio Grande do Sul, 90035-903

Other trials in Brazil

About this study

Official title: A Randomized Clinical Trial to Evaluate the Effects of Losartan on Cardiovascular Disease in Patients With Mucopolysaccharidoses IV A and VI

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.

Read the 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.

Being tested
Losartan, Placebo
Keywords
Mucopolysaccharidoses, Losartan, Aortic root dilatation, Echocardiogram, MPS IV, MPS VI
Medical subject headings
Mucopolysaccharidosis IV, Mucopolysaccharidosis VI, Mucopolysaccharidoses

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LosartanDrug

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

  • PlaceboDrug

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

Study groups in NCT03632213
Study groupRoleWhat they receive
LosartanActive comparatorLosartan group: 15 patients, both sexes, will receive Losartan 0.4 to 1.4 mg/kg/day orally for 12 months.
Receives: Drug: Losartan
PlaceboPlacebo comparatorPlacebo group:15 patients, both sexes, will receive oral placebo for 12 months.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Adverse events related to losartan use

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

    Measured: 12 months

Secondary outcomes (20)

  1. 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.

    Measured: 12 months

  2. 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

    Measured: 12 months

  3. Changes of serum levels of brain-type natriuretic peptide (BNP)

    Changes of serum levels of brain-type natriuretic peptide between baseline and 12 months

    Measured: 12 months

  4. 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

    Measured: 12 months

  5. 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

    Measured: 12 months

  6. 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

    Measured: 12 months

  7. 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

    Measured: 12 months

  8. Changes of serum levels of Endocan-1 (ESM-1)

    Changes of serum levels of Endocan-1 (ESM-1) between baseline and 12 months

    Measured: 12 months

  9. Changes of serum levels of Placental growth factor (PLGF)

    Changes of serum levels ofPlacental growth factor (PLGF) between baseline and 12 months

    Measured: 12 months

  10. 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

    Measured: 12 months

  11. 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

    Measured: 12 months

  12. Changes of serum levels of Oncostatin M

    Changes of serum levels of Oncostatin M between baseline and 12 months

    Measured: 12 months

  13. Changes of serum levels of Troponin I

    Changes of serum levels of Troponin I between baseline and 12 months

    Measured: 12 months

  14. 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.

    Measured: 12 months

  15. 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.

    Measured: 12 months

  16. 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.

    Measured: 12 months

  17. Changes in ejection fraction

    Alteration of the ejection fraction measurement as assessed by echocardiography between the baseline and 12 months.

    Measured: 12 months

  18. 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.

    Measured: 12 months

  19. Changes in E/A ratio

    Alteration of the parameter E/A ratio as assessed by echocardiography between the baseline and 12 months .

    Measured: 12 months

  20. Changes in E/e' ratio

    Alteration of the parameter E/e' ratio as assessed by echocardiography between the baseline and 12 months.

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Aug 2018
  2. Study start7 Nov 2018
  3. Primary completion4 May 2023 (estimated)
  4. Study completion3 Aug 2023 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03632213
Sponsor's protocol ID
17-0685
Status last verified
Dec 2022
First submitted
3 Aug 2018
Last updated
19 Dec 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Losartan in people with Mucopolysaccharidosis IV A and Mucopolysaccharidosis VI, run by Hospital de Clinicas de Porto Alegre at 1 site in Brazil.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 19 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adverse events related to losartan use (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03632213.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2022.

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