Sickle Cell DiseasePhase 1/2NCT03599609
Central Nervous System Vascular Changes in Adult Sickle Cell Disease and the Effect of Treatment With Simvastatin
A Phase 1/2 study testing Simvastatin 40mg in people with Sickle Cell Disease and Stroke, run by University of Campinas, Brazil at 1 site in Brazil.
Trial 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. Read more about this study
- Who is it for?
- Ages 35 years and older
- Conditions the study is for
- Sickle Cell Disease, Stroke
- What is being tested?
- Simvastatin 40mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteBrazil
- Study dates
- 5 Mar 2018to Jul 2021
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of Sickle Cell Disease
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
Brazil1 site
Hematology and Transfusion Medicine Center
Campinas, São Paulo, 13083-870
About this study
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
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
- Being tested
- Simvastatin 40mg
- Medical subject headings
- Anemia, Sickle Cell, Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Simvastatin 40mgDrug
Simvastatin 40mg, once daily
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Treatment: Simvastatin 40mg/day Receives: Drug: Simvastatin 40mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Stroke prevention
Number of patients in the cohort presenting srtoke or silent infarction detected at MRI
Measured: 5 years
Secondary outcomes (4)
Improvement of hemodynamic parameters in MRI:velocity
Evaluation of changes in vessel segment-averaged velocity (cm/s) in the Circle of Willis
Measured: 1 year
Improvement of hemodynamic parameters in MRI: lumen area
Evaluation of changes in vessel lumen area (mm2) in the Circle of Willis
Measured: 1 year
Improvement of hemodynamic parameters in MRI: flow
Evaluation of changes in flow (ml/s) in the Circle of Willis
Measured: 1 year
Improvement of hemodynamic parameters in MRI: endothelial shear stress
Evaluation of changes in endothelial shear stress (Pa) in the Circle of Willis
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2018
- Study start5 Mar 2018
- Primary completion14 Jan 2020
- Study completionJul 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Campinas, Brazil
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Bruno Deltreggia Benites, University of Campinas, Brazil
- Investigators
- Bruno Benites, MD, Principal investigator, University of Campinas, Brazil
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03599609
- Sponsor's protocol ID
- 2.487.922
- Status last verified
- Oct 2020
- First submitted
- 2 Jul 2018
- Last updated
- 12 Oct 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03599609
- Acronym / sponsor ID
- 2.487.922
- Conditions
- Sickle Cell Disease, Stroke
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 28 participants (actual)
- Lead sponsor
- University of Campinas, BrazilUniversity, hospital or other
- Study start
- 5 Mar 2018 (actual)
- Primary completion
- 14 Jan 2020 (actual)
- Study completion
- Jul 2021 (estimated)
- First posted
- 26 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: Simvastatin 40mgTreatment: Simvastatin 40mg/day |
Who may qualify
- Ages
- 35 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Diagnosis of Sickle Cell Disease
Key exclusion criteria (4 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Simvastatin 40mgSimvastatin 40mg, once daily | Drug | Treatment |
Primary outcome
Stroke prevention
Time frame: 5 years
Number of patients in the cohort presenting srtoke or silent infarction detected at MRI
4 secondary outcomes
Improvement of hemodynamic parameters in MRI:velocity
Time frame: 1 year
Improvement of hemodynamic parameters in MRI: lumen area
Time frame: 1 year
Improvement of hemodynamic parameters in MRI: flow
Time frame: 1 year
Improvement of hemodynamic parameters in MRI: endothelial shear stress
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bruno Benites, MD principal investigator
University of Campinas, Brazil
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Simvastatin 40mg in people with Sickle Cell Disease and Stroke, run by University of Campinas, Brazil at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Stroke prevention (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2020.