Clinical trial NCT03599609: Central Nervous System Vascular Changes in Adult Sickle Cell Disease and the Effect of Treatment With Simvastatin
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Sickle Cell Disease
Stroke
Lead sponsor: University of Campinas, Brazil
Sponsor class: OTHER
First posted: 2018-07-26
Enrollment: 28
Sex: ALL
Minimum age (years): 35
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.


Eligibility 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)

Primary outcomes:
measure: Stroke prevention
timeFrame: 5 years
Secondary outcomes:
measure: Improvement of hemodynamic parameters in MRI:velocity
timeFrame: 1 year
measure: Improvement of hemodynamic parameters in MRI: lumen area
timeFrame: 1 year
measure: Improvement of hemodynamic parameters in MRI: flow
timeFrame: 1 year
measure: Improvement of hemodynamic parameters in MRI: endothelial shear stress
timeFrame: 1 year
Other outcomes:
Locations:
city: Campinas
country: Brazil
facility: Hematology and Transfusion Medicine Center
state: São Paulo
Study officials:
affiliation: University of Campinas, Brazil
name: Bruno Benites, MD
role: PRINCIPAL_INVESTIGATOR
References: