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

NCT03599609 | Unknown Phase 1

• 1 other identifier: 2.487.922
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Stroke prevention

  Number of patients in the cohort presenting srtoke or silent infarction detected at MRI

  5 years

Secondary Outcomes (4)

• 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

Study Arms (1)

Treatment

EXPERIMENTAL

Treatment: Simvastatin 40mg/day

Drug: Simvastatin 40mg

Interventions

Simvastatin 40mg DRUG

Simvastatin 40mg, once daily

Treatment

Eligibility Criteria

• Age: 35 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of Sickle Cell Disease

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Campinas, Brazil: lead

Study Sites (1)

Hematology and Transfusion Medicine Center

Campinas, São Paulo, 13083-870, Brazil

Location

MeSH Terms

Conditions

Anemia, Sickle Cell; Stroke

Interventions

Simvastatin

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Bruno Benites, MD

  University of Campinas, Brazil

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 2, 2018
• First Posted: July 26, 2018
• Study Start: March 5, 2018
• Primary Completion: January 14, 2020
• Study Completion: July 1, 2021
• Last Updated: October 12, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)