Sickle Cell DiseasePhase 1/2NCT01702246
Effect of Simvastatin Treatment on Vaso-occlusive Pain in Sickle Cell Disease
A Phase 1/2 study testing Simvastatin in people with Sickle Cell Disease, run by UCSF Benioff Children's Hospital Oakland at 1 site in United States.
Trial summary
The purpose of this study is to determine whether simvastatin is effective in reducing the frequency and intensity of vaso-occlusive pain episodes in patients with sickle cell disease. Read more about this study
- Who is it for?
- Ages 10 years and older
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Simvastatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2012to Jun 2015
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 10 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Sickle cell disease (HbSS or S/β0 thalassemia)
- ≥ 3 vaso-occlusive pain episodes in the year prior to enrollment
- Age ≥ 10 years
- Weight > 30 kg
Who cannot join
- Creatine kinase (CK) > UNL
- Total cholesterol < 90 mg/dL, or triglycerides <30mg/dL
- Renal dysfunction (Creatinine > 1.5-fold UNL)
- Hepatic dysfunction (ALT > 2-fold UNL)
- Treatment with drugs having known metabolic interactions with statins within the past 30 days
- Vaso-occlusive pain requiring hospitalization within past 30 days
Show all 12Show fewer
- Red blood cell transfusion within the past 30 days
- Pregnancy/lactation
- Musculoskeletal disorder associated with an elevated CK level
- Past or present history of substance abuse (alcohol, cocaine, amphetamines, heroin)
- Chronic pain caused by avascular necrosis of the bone (AVN) or leg ulcers, and pain due to trauma or causes other than SCD.
- Major cognitive or neurological impairments that may hamper the ability to use the smartphone or complete the electronic pain diary in this study
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital and Research Center Oakland
Oakland, California, 94609
About this study
Official title: Phase 2 Study of Simvastatin Treatment Effects on Vaso-occlusive Pain in Sickle Cell Disease
The purpose of this study is to determine whether simvastatin is effective in reducing the frequency and intensity of vaso-occlusive pain episodes in patients with sickle cell disease.
Read the detailed description
Sickle cell disease (SCD) is characterized by recurrent vaso-occlusive episodes and a chronic inflammatory state leading to progressive multi-organ injury. The pathophysiology of SCD is related to endothelial dysfunction driven largely by impaired nitric oxide (NO) homeostasis and chronic inflammation. Through multiple mechanisms, including upregulation of NO, statins have been shown to confer protection from endothelial injury, independent of their cholesterol-lowering properties.
By inhibiting inflammation and several common pathways leading to vascular damage,simvastatin may help prevent the acute and chronic complications of SCD. The objective of this study is to determine whether our preliminary results showing simvastatin-associated reductions in plasma markers of vascular injury will translate into a reduction in vaso-occlusive pain episodes in patients with SCD. A web-based, smartphone-accessible electronic pain diary will be used to monitor frequency and intensity of vaso-occlusive pain in SCD patients treated with a single daily dose of simvastatin.
- Conditions
- Sickle Cell Disease
- Being tested
- Simvastatin
- Keywords
- sickle cell disease, statins, vaso-occlusive pain, inflammation, biomarkers
- Medical subject headings
- Anemia, Sickle Cell, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SimvastatinDrug
Also called Zocor
40 mg, orally, once daily for 3 months
| Study group | Role | What they receive |
|---|---|---|
| simvastatin | Experimental | Simvastatin (Zocor), 40mg tablet, 40mg orally once daily, for 3 months Receives: Drug: Simvastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Frequency of Vaso-occlusive Pain Events, Before and After Treatment With Simvastatin
The effect of simvastatin treatment will be assessed by measuring the difference from baseline in the mean frequency (and intensity) of vaso-occlusive pain events, after treatment with simvastatin. Pain rate (proportion of pain days) was defined as the number of days reported with sickle cell disease-related pain divided by the number of daily pain diaries completed.
Measured: Baseline and 3 months
Secondary outcomes (2)
Change in Plasma High Sensitivity C-reactive Protein
Mean difference in plasma high sensitivity C-reactive protein level, before and after treatment with simvastatin
Measured: Baseline and 3 months
Change From Baseline in Total Cholesterol Level After Treatment With Simvastatin
Measured: Baseline and 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2012 (estimated)
- Study startFeb 2012
- Primary completionMay 2015
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- UCSF Benioff Children's Hospital Oakland
- Sponsor type
- University, hospital or other
- Collaborators
- University of California, Los Angeles
- Responsible party
- Principal investigator, Carolyn Hoppe, UCSF Benioff Children's Hospital Oakland
- Investigators
- Carolyn Hoppe, MD, Principal investigator, UCSF Benioff Children's Hospital Oakland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01702246
- Sponsor's protocol ID
- DDCF-ICRA-2011
- Status last verified
- Jan 2016
- First submitted
- 4 Oct 2012
- Last updated
- 19 Dec 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No: publication
Publications
Hoppe C, Kuypers F, Larkin S, Hagar W, Vichinsky E, Styles L. A pilot study of the short-term use of simvastatin in sickle cell disease: effects on markers of vascular dysfunction. Br J Haematol. 2011 Jun;153(5):655-63. doi: 10.1111/j.1365-2141.2010.08480.x. Epub 2011 Apr 8.
PubMed 21477202
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Study of Simvastatin Treatment Effects on Vaso-occlusive Pain in Sickle Cell Disease
- ClinicalTrials.gov ID
- NCT01702246
- Acronym / sponsor ID
- DDCF-ICRA-2011
- Conditions
- Sickle Cell Disease
- Keywords
- sickle cell disease, statins, vaso-occlusive pain, inflammation, biomarkers
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- UCSF Benioff Children's Hospital OaklandUniversity, hospital or other
- Collaborators
- University of California, Los Angeles
- Study start
- Feb 2012
- Primary completion
- May 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 8 Oct 2012 (estimated)
- Results
- Posted 19 Dec 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether simvastatin is effective in reducing the frequency and intensity of vaso-occlusive pain episodes in patients with sickle cell disease.
Detailed description
Sickle cell disease (SCD) is characterized by recurrent vaso-occlusive episodes and a chronic inflammatory state leading to progressive multi-organ injury. The pathophysiology of SCD is related to endothelial dysfunction driven largely by impaired nitric oxide (NO) homeostasis and chronic inflammation. Through multiple mechanisms, including upregulation of NO, statins have been shown to confer protection from endothelial injury, independent of their cholesterol-lowering properties.
By inhibiting inflammation and several common pathways leading to vascular damage,simvastatin may help prevent the acute and chronic complications of SCD. The objective of this study is to determine whether our preliminary results showing simvastatin-associated reductions in plasma markers of vascular injury will translate into a reduction in vaso-occlusive pain episodes in patients with SCD. A web-based, smartphone-accessible electronic pain diary will be used to monitor frequency and intensity of vaso-occlusive pain in SCD patients treated with a single daily dose of simvastatin.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| simvastatin | Experimental | Drug: SimvastatinSimvastatin (Zocor), 40mg tablet, 40mg orally once daily, for 3 months |
Who may qualify
- Ages
- 10 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Sickle cell disease (HbSS or S/β0 thalassemia)
- ≥ 3 vaso-occlusive pain episodes in the year prior to enrollment
- Age ≥ 10 years
- Weight > 30 kg
Key exclusion criteria (12 listed)
- Creatine kinase (CK) > UNL
- Total cholesterol < 90 mg/dL, or triglycerides <30mg/dL
- Renal dysfunction (Creatinine > 1.5-fold UNL)
- Hepatic dysfunction (ALT > 2-fold UNL)
- Treatment with drugs having known metabolic interactions with statins within the past 30 days
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 |
|---|---|---|
| SimvastatinAlso: Zocor40 mg, orally, once daily for 3 months | Drug | simvastatin |
Primary outcome
Change in Frequency of Vaso-occlusive Pain Events, Before and After Treatment With Simvastatin
Time frame: Baseline and 3 months
The effect of simvastatin treatment will be assessed by measuring the difference from baseline in the mean frequency (and intensity) of vaso-occlusive pain events, after treatment with simvastatin. Pain rate (proportion of pain days) was defined as the number of days reported with sickle cell disease-related pain divided by the number of daily pain diaries completed.
2 secondary outcomes
Change in Plasma High Sensitivity C-reactive Protein
Time frame: Baseline and 3 months
Change From Baseline in Total Cholesterol Level After Treatment With Simvastatin
Time frame: Baseline and 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21477202Hoppe C, Kuypers F, Larkin S, Hagar W, Vichinsky E, Styles L. A pilot study of the short-term use of simvastatin in sickle cell disease: effects on markers of vascular dysfunction. Br J Haematol. 2011 Jun;153(5):655-63. doi: 10.1111/j.1365-2141.2010.08480.x. Epub 2011 Apr 8.
- Individual participant dataSharing planned: No. publication
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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.
Carolyn Hoppe, MD principal investigator
UCSF Benioff Children's Hospital Oakland
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 in people with Sickle Cell Disease, run by UCSF Benioff Children's Hospital Oakland at 1 site in United States.
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 4 inclusion and 12 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: finished, as of the sponsor's last update on 19 Dec 2016. 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 United States. 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?
Yes. Results are posted in the registry (first posted 19 Dec 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Frequency of Vaso-occlusive Pain Events, Before and After Treatment With Simvastatin (time frame: Baseline and 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01702246, which also lists 1 linked publication.
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 19 Dec 2016.