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

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

Sponsors

Lead Sponsor: University of Campinas, Brazil

Source 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.

Overall Status Active, not recruiting
Start Date March 5, 2018
Completion Date July 2024
Primary Completion Date January 2020
Phase Phase 1/Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Stroke prevention 5 years
Secondary Outcome
Measure Time Frame
Improvement of hemodynamic parameters in MRI:velocity 1 year
Improvement of hemodynamic parameters in MRI: lumen area 1 year
Improvement of hemodynamic parameters in MRI: flow 1 year
Improvement of hemodynamic parameters in MRI: endothelial shear stress 1 year
Enrollment 28
Condition
Intervention

Intervention Type: Drug

Intervention Name: Simvastatin 40mg

Description: Simvastatin 40mg, once daily

Arm Group Label: Treatment

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)

Gender: All

Minimum Age: 35 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Bruno Benites, MD Principal Investigator University of Campinas, Brazil
Location
Facility: Hematology and Transfusion Medicine Center
Location Countries

Brazil

Verification Date

October 2019

Responsible Party

Type: Principal Investigator

Investigator Affiliation: University of Campinas, Brazil

Investigator Full Name: Bruno Deltreggia Benites

Investigator Title: Principal Investigator

Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Treatment

Type: Experimental

Description: Treatment: Simvastatin 40mg/day

Patient Data No
Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Prevention

Masking: None (Open Label)

Source: ClinicalTrials.gov