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

NCT ID: NCT03599609

Last Updated: 2020-10-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-05
• Study Completion Date: 2021-07-31

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.

Conditions

Sickle Cell Disease; Stroke

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Treatment

Treatment: Simvastatin 40mg/day

Group Type: EXPERIMENTAL

Simvastatin 40mg

Intervention Type: DRUG

Simvastatin 40mg, once daily

Interventions

Simvastatin 40mg

Simvastatin 40mg, once daily

Intervention Type: DRUG

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)

• Minimum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Campinas, Brazil

OTHER

Sponsor Role: lead

Responsible Party

Bruno Deltreggia Benites

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bruno Benites, MD

Role: PRINCIPAL_INVESTIGATOR

University of Campinas, Brazil

Locations

Hematology and Transfusion Medicine Center

Campinas, São Paulo, Brazil

Countries

Brazil

Other Identifiers

2.487.922

Identifier Type: -

Identifier Source: org_study_id