Central Nervous System Vascular Changes Evidenced by Magnetic Resonance Imaging in Adult Patients With Sickle Cell Disease and the Effect of Treatment With Simvastatin

Locations

1 Brazil site

Age

> 35 Years

Phase

Phase 1/Phase 2

Study type

Interventional

Gender

All

Interventions

Drug

Compensation

Unknown

About the study

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.

participation requirements

– Diagnosis of Sickle Cell Disease

participation restrictions

– 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)

Locations

  • Campinas, São Paulo, Brazil, Hematology and Transfusion Medicine Center, 13083-870