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Central Nervous System Vascular Changes in Adult Sickle Cell Disease and the Effect of Treatment With Simvastatin

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ClinicalTrials.gov Identifier: NCT03599609
Recruitment Status : Recruiting
First Posted : July 25, 2018
Last Update Posted : July 25, 2018
Sponsor:
Information provided by (Responsible Party):
Bruno Deltreggia Benites, University of Campinas, Brazil

Brief Summary:
Stroke is a frequent complication of sickle cell disease (SCD), with varying levels of central nervous system (CNS) involvement. The summation of several ischemic events, even when silent, can lead to devastating consequences, from reduced academic performance to physical dependence. Despite knowledge that brain flow velocities evaluated by Doppler ultrasound identify pediatric SCD patients at a greater stroke risk (Adams et al, NEJM 1998; 339:5-11), this method is not able to predict the occurrence of strokes in adults. There is also no consensus on the management of adult patients in relation to primary and secondary prevention. The aim of this study is to evaluate the effects of the administration of Simvastatin on CNS structural and functional vascular changes in 30 adult patients with SCD (SS and Sβ), above 35 years of age, observed through Magnetic Resonance Imaging (MRI). The data on the effect of simvastatin on disease manifestations is quite scarce, however this drug reportedly significantly reduces plasma concentrations of adhesion molecules and inflammatory markers, such as E-selectin, VEGF, CRP and IL-6 (Hoppe et al, BJH 2011; 153:655-663; Hoppe et al, BJH 2017;177:620-629). Thus, in addition to the search for early diagnostic markers and risk stratification for primary or recurrent stroke, we will also compare CNS images before and 12 months after the administration of Simvastatin. The drug alter stroke recurrence rates in the general adult population, but their effects on vascular changes in patients with SCD have not yet been adequately elucidated. This is particularly important because these are low cost drugs which present good tolerability, and could be part of the therapeutic arsenal of SCD, even in low income settings. Concomitantly with the CNS evaluation, this study also intends to investigate molecular pathways that may be affected by the drugs. We will evaluate microvesicle release patterns, as well as the content of microRNAs possibly involved in the occurrence of stroke, in addition to metabolomic studies and plasma cytokine profile.

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Stroke Drug: Simvastatin 40mg Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Central Nervous System Vascular Changes Evidenced by Magnetic Resonance Imaging in Adult Patients With Sickle Cell Disease and the Effect of Treatment With Simvastatin
Actual Study Start Date : March 5, 2018
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : July 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Simvastatin

Arm Intervention/treatment
Experimental: Treatment
Treatment: Simvastatin 40mg/day
Drug: Simvastatin 40mg
Simvastatin 40mg, once daily




Primary Outcome Measures :
  1. Stroke prevention [ Time Frame: 5 years ]
    Number of patients in the cohort presenting srtoke or silent infarction detected at MRI


Secondary Outcome Measures :
  1. Improvement of hemodynamic parameters in MRI:velocity [ Time Frame: 1 year ]
    Evaluation of changes in vessel segment-averaged velocity (cm/s) in the Circle of Willis

  2. Improvement of hemodynamic parameters in MRI: lumen area [ Time Frame: 1 year ]
    Evaluation of changes in vessel lumen area (mm2) in the Circle of Willis

  3. Improvement of hemodynamic parameters in MRI: flow [ Time Frame: 1 year ]
    Evaluation of changes in flow (ml/s) in the Circle of Willis

  4. Improvement of hemodynamic parameters in MRI: endothelial shear stress [ Time Frame: 1 year ]
    Evaluation of changes in endothelial shear stress (Pa) in the Circle of Willis



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Ages Eligible for Study:   35 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of Sickle Cell Disease

Exclusion Criteria:

  • Previous stroke
  • Some relevant concomitant clinical condition (cancer, AIDS, inflammatory / autoimmune diseases, etc.).
  • Pregnancy
  • Individuals considered to be vulnerable (minors,institutionalized individuals, patients with a history of psychiatric illness with cognitive impairment or incapacity)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03599609


Contacts
Contact: Bruno Benites, MD +551935218613 benites@unicamp.br
Contact: Sara Saad, MD, PhD +551935218740 sara@unicamp.br

Locations
Brazil
Hematology and Transfusion Medicine Center Recruiting
Campinas, São Paulo, Brazil, 13083-870
Contact: Bruno Benites, MD    +5519997962346    benites@unicamp.br   
Sponsors and Collaborators
University of Campinas, Brazil
Investigators
Principal Investigator: Bruno Benites, MD University of Campinas, Brazil

Responsible Party: Bruno Deltreggia Benites, Principal Investigator, University of Campinas, Brazil
ClinicalTrials.gov Identifier: NCT03599609     History of Changes
Other Study ID Numbers: 2.487.922
First Posted: July 25, 2018    Key Record Dates
Last Update Posted: July 25, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Simvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors