ThalassemiaCVRNCT03715972
Cerebrovascular Reserve and White Matter Disease in Patients with Chronic Anemia
An observational study of Thalassemia and Sickle Cell Disease, run by Children's Hospital Los Angeles at 1 site in United States.
Trial summary
This is primarily an observational trial in patients with chronic anemia syndromes (sickle cell disease and thalassemia) and control subjects. The key purpose is to understand how brain blood flow reserve (the ability of the brain to increase its flow in response to stress) is altered in patients with chronic anemia. Read more about this study
- Who is it for?
- Ages 7 years and olderHealthy volunteers can take part
- Conditions the study is for
- Thalassemia, Sickle Cell Disease, Healthy Controls
- What is being tested?
- Hydroxyurea and Acetazolamide
- How many people
- 165 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jul 2018to 31 Dec 2022
- Phase
- Observational
- 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 7 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: sickle cell disease: non-transfused, simple transfused, exchange transfusion Non-sickle Cell Anemia: Non- transfused and transfused healthy controls
Who may be able to join
- Diagnosis of sickle cell disease (genotype SS, SC, or SB0), thalassemia (transfusion dependent or transfusion independent), or normal control subject that are ≥18yrs, ethnicity, and sex matched to the sickle cell disease population.
- Ability to tolerate a one hour MRI examination.
- Age equal to or greater than 7 years old for Anemia groups.
- Agreeable to use an approved method of contraception for the entire duration of hydroxyurea usage if accepted onto the hydroxyurea substudy (male or female of childbearing potential)
Who cannot join
- Hospitalization within one month
- Contraindication to acetazolamide use (seizures)
- Severe claustrophobia.
- Pregnancy or nursing (a negative HCG (pregnancy) test must be obtained prior to MRI)
- As a result of medical review, physical examination or screening investigations, the Principal Investigator (PI) considers the subject unfit for the study
- No fixed address
- In control subjects, chronic hepatitis, diabetes, hypertension, coronary artery disease, cognitively impaired or developmental delay
Trial locations and contacts
1 site in 1 country.
About this study
This is primarily an observational trial in patients with chronic anemia syndromes (sickle cell disease and thalassemia) and control subjects. The key purpose is to understand how brain blood flow reserve (the ability of the brain to increase its flow in response to stress) is altered in patients with chronic anemia. Since this parameter may depend on anemia severity, we will perform the MRI monitoring prior to and following clinically indicated transfusions in a subset of patients. Most patients will already be prescribed hydroxyurea as part of their standard of care. Since hydroxyurea could impact brain blood flow, there is also a small pilot study (20 patients, nonrandomized, open label) where MRI imaging will be performed prior to and following administration of hydroxyurea up to maximum tolerated dose. The study will enroll 90 adult subjects with transfusion independent sickle cell disease (70 SS, 10 SC, 10 Sβ0) and 60 patients with transfusion-dependent sickle cell disease. It will also include 10 transfusion independent thalassemia patients and 20 transfusion dependent thalassemia patients as well as 40 control subjects recruited from first degree relatives of the sickle cell disease population. All eligible subjects will be asked to provide informed consent before participating in the study.
Read the detailed description
This is primarily an observational trial in patients with chronic anemia syndromes (sickle cell disease and thalassemia) and control subjects. The key purpose is to understand how brain blood flow reserve (the ability of the brain to increase its flow in response to stress) is altered in patients with chronic anemia. Since this parameter may depend on anemia severity, we will perform the MRI monitoring prior to and following clinically indicated transfusions in a subset of patients. Most patients will already be prescribed hydroxyurea as part of their standard of care. Since hydroxyurea could impact brain blood flow, there is also a small pilot study (20 patients, nonrandomized, open label) where MRI imaging will be performed prior to and following administration of hydroxyurea up to maximum tolerated dose. The study will enroll 90 adult subjects with transfusion independent sickle cell disease (70 SS, 10 SC, 10 Sβ0) and 60 patients with transfusion-dependent sickle cell disease. It will also include 10 transfusion independent thalassemia patients and 20 transfusion dependent thalassemia patients as well as 40 control subjects recruited from first degree relatives of the sickle cell disease population. All eligible subjects will be asked to provide informed consent before participating in the study.
Treatment:
All patients will undergo baseline phlebotomy, brain MRI, and neurocognitive testing. The MRI will include measurements of brain blood flow prior to and following administration of 16 mg/kg of acetazolamide to maximally vasodilate the cerebral vasculature. All transfusion dependent patients will have their MRI performed immediately prior to a routinely scheduled transfusion at their hemoglobin nadir. 20 sickle cell disease patients on chronic simple transfusions and 10 thalassemia patients on chronic simple transfusions will undergo repeat MRI assessment of cerebral blood flow and reactivity following their clinically indicated blood transfusion. 10 sickle cell disease patients on exchange transfusions will undergo repeat MRI assessment of cerebral blood flow and reactivity following their clinically indicated exchange transfusion; this transfusion will be performed to lower their hemoglobin S percentage by 25% points while keeping the total hemoglobin unchanged (isocrit exchange). 20 non transfusion dependent sickle cell disease patients not already receiving hydroxyurea will be placed on hydroxyurea following their baseline exam and titrated to maximal tolerated dose. They will then undergo a repeat MRI within two months of reaching that dose and be given the option to continue on hydroxyurea or stop.
Safety Assessment:
All patients will have a physician present during the MRI examination to monitor vital signs and response to acetazolamide. Patients placed onto hydroxyurea will have monthly study visits with monitoring of complete blood count, vital signs, complete metabolic panel, and hemoglobin electrophoresis. Adverse events will be assessed at every study visit after the first dose through to the last subject visit.
Efficacy Assessments:
Baseline cerebrovascular reserve (CVR) predictors will be assessed by multivariate regression after appropriate transformations. Potential independent predictors include oxygen content, hemoglobin subtype, as well as markers of hemolysis, inflammation, and iron overload.
- Conditions
- Thalassemia, Sickle Cell Disease, Healthy Controls
- Being tested
- Hydroxyurea, Acetazolamide
- Keywords
- cerebrovascular reserve, white matter disease in patients with chronic anemia
- Medical subject headings
- Thalassemia, Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HydroxyureaDrug
Also called Hydrea
info included in arm group
AcetazolamideDrug
Also called Diamox
Acetazolamide will not be considered a treatment; however, it will be used as a tool to help measure cerebralvascular reserve. A dose of 16 mg/kg ACZ will be administered with a maximum of 1400 mg.
| Study group | Role | What they receive |
|---|---|---|
| Anemia Observation | The study will enroll 90 adult subjects with transfusion independent sickle cell disease (70 SS, 10 SC, 10 Sβ0) and 60 patients with transfusion-dependent sickle cell disease. It will also include 10 transfusion independent thalassemia patients and 20 transfusion dependent thalassemia patients. Diamox (acetazolamide) will be administered during MRI. Receives: Drug: Acetazolamide | |
| Anemia Intervention | Most patients will already be prescribed hydroxyurea as part of their standard of care. Since hydroxyurea could impact brain blood flow, there is also a small pilot study (20 patients, nonrandomized, open label) where MRI imaging will be performed prior to and following administration of hydroxyurea up to maximum tolerated dose.
non transfusion dependent sickle cell disease patients not already receiving hydroxyurea will be placed on hydroxyurea following their baseline exam and titrated to maximal tolerated dose. They will then undergo a repeat MRI within two months of reaching that dose and be given the option to continue on hydroxyurea or stop. Receives: Drug: Hydroxyurea; Drug: Acetazolamide | |
| Healthy Controls | 40 control subjects recruited from first degree relatives of the sickle cell disease population. Diamox (acetazolamide) will be administered during MRI. Receives: Drug: Acetazolamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
CVR response to transfusion
Cerebral vascular flow reserve will be assessed prior to and following a regularly scheduled blood transfusion
Measured: 3-5 days
CVR response to hydroxyurea therapy
Change in cerebral vascular reserve at baseline and after initiation of hydroxyurea titrated to maximum tolerated dose
Measured: 2-4 months
Secondary outcomes (1)
Predictors of CVR response
We will determine what factors determine cerebral blood flow response to diamox vasodilator challenge
Measured: Single study visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2018
- Study start15 Jul 2018
- Primary completion31 Dec 2022
- Study completion31 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ThalassemiaStudies of the same condition, open and under way.
- More trials run by Children's Hospital Los AngelesThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 165 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Vanderbilt University Medical Center
- Responsible party
- Principal investigator, John C. Wood, Children's Hospital Los Angeles
- Investigators
- John C Wood, M.D., PhD, Principal investigator, CHLA/USC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03715972
- Sponsor's protocol ID
- CHLA-17-00496
- Other IDs
- 1R01HL136484-01A1
- Acronym
- CVR
- Status last verified
- May 2023
- First submitted
- 20 Feb 2018
- Last updated
- 30 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cerebrovascular Reserve and White Matter Disease in Patients with Chronic Anemia
- ClinicalTrials.gov ID
- NCT03715972
- Acronym / sponsor ID
- CVR / CHLA-17-00496
- Conditions
- Thalassemia, Sickle Cell Disease, Healthy Controls
- Keywords
- cerebrovascular reserve, white matter disease in patients with chronic anemia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 165 participants (actual)
- Lead sponsor
- Children's Hospital Los AngelesUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Vanderbilt University Medical Center
- Study start
- 15 Jul 2018 (actual)
- Primary completion
- 31 Dec 2022 (actual)
- Study completion
- 31 Dec 2022 (actual)
- First posted
- 23 Oct 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.
This is primarily an observational trial in patients with chronic anemia syndromes (sickle cell disease and thalassemia) and control subjects. The key purpose is to understand how brain blood flow reserve (the ability of the brain to increase its flow in response to stress) is altered in patients with chronic anemia. Since this parameter may depend on anemia severity, we will perform the MRI monitoring prior to and following clinically indicated transfusions in a subset of patients. Most patients will already be prescribed hydroxyurea as part of their standard of care. Since hydroxyurea could impact brain blood flow, there is also a small pilot study (20 patients, nonrandomized, open label) where MRI imaging will be performed prior to and following administration of hydroxyurea up to maximum tolerated dose. The study will enroll 90 adult subjects with transfusion independent sickle cell disease (70 SS, 10 SC, 10 Sβ0) and 60 patients with transfusion-dependent sickle cell disease. It will also include 10 transfusion independent thalassemia patients and 20 transfusion dependent thalassemia patients as well as 40 control subjects recruited from first degree relatives of the sickle cell disease population. All eligible subjects will be asked to provide informed consent before participating in the study.
Detailed description
This is primarily an observational trial in patients with chronic anemia syndromes (sickle cell disease and thalassemia) and control subjects. The key purpose is to understand how brain blood flow reserve (the ability of the brain to increase its flow in response to stress) is altered in patients with chronic anemia. Since this parameter may depend on anemia severity, we will perform the MRI monitoring prior to and following clinically indicated transfusions in a subset of patients. Most patients will already be prescribed hydroxyurea as part of their standard of care. Since hydroxyurea could impact brain blood flow, there is also a small pilot study (20 patients, nonrandomized, open label) where MRI imaging will be performed prior to and following administration of hydroxyurea up to maximum tolerated dose. The study will enroll 90 adult subjects with transfusion independent sickle cell disease (70 SS, 10 SC, 10 Sβ0) and 60 patients with transfusion-dependent sickle cell disease. It will also include 10 transfusion independent thalassemia patients and 20 transfusion dependent thalassemia patients as well as 40 control subjects recruited from first degree relatives of the sickle cell disease population. All eligible subjects will be asked to provide informed consent before participating in the study.
Treatment:
All patients will undergo baseline phlebotomy, brain MRI, and neurocognitive testing. The MRI will include measurements of brain blood flow prior to and following administration of 16 mg/kg of acetazolamide to maximally vasodilate the cerebral vasculature. All transfusion dependent patients will have their MRI performed immediately prior to a routinely scheduled transfusion at their hemoglobin nadir. 20 sickle cell disease patients on chronic simple transfusions and 10 thalassemia patients on chronic simple transfusions will undergo repeat MRI assessment of cerebral blood flow and reactivity following their clinically indicated blood transfusion. 10 sickle cell disease patients on exchange transfusions will undergo repeat MRI assessment of cerebral blood flow and reactivity following their clinically indicated exchange transfusion; this transfusion will be performed to lower their hemoglobin S percentage by 25% points while keeping the total hemoglobin unchanged (isocrit exchange). 20 non transfusion dependent sickle cell disease patients not already receiving hydroxyurea will be placed on hydroxyurea following their baseline exam and titrated to maximal tolerated dose. They will then undergo a repeat MRI within two months of reaching that dose and be given the option to continue on hydroxyurea or stop.
Safety Assessment:
All patients will have a physician present during the MRI examination to monitor vital signs and response to acetazolamide. Patients placed onto hydroxyurea will have monthly study visits with monitoring of complete blood count, vital signs, complete metabolic panel, and hemoglobin electrophoresis. Adverse events will be assessed at every study visit after the first dose through to the last subject visit.
Efficacy Assessments:
Baseline cerebrovascular reserve (CVR) predictors will be assessed by multivariate regression after appropriate transformations. Potential independent predictors include oxygen content, hemoglobin subtype, as well as markers of hemolysis, inflammation, and iron overload.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Anemia Observation | – | Drug: AcetazolamideThe study will enroll 90 adult subjects with transfusion independent sickle cell disease (70 SS, 10 SC, 10 Sβ0) and 60 patients with transfusion-dependent sickle cell disease. It will also include 10 transfusion independent thalassemia patients and 20 transfusion dependent thalassemia patients. Diamox (acetazolamide) will be administered during MRI. |
| Anemia Intervention | – | Drug: Hydroxyurea, Drug: AcetazolamideMost patients will already be prescribed hydroxyurea as part of their standard of care. Since hydroxyurea could impact brain blood flow, there is also a small pilot study (20 patients, nonrandomized, open label) where MRI imaging will be performed prior to and following administration of hydroxyurea up to maximum tolerated dose. non transfusion dependent sickle cell disease patients not already receiving hydroxyurea will be placed on hydroxyurea following their baseline exam and titrated to maximal tolerated dose. They will then undergo a repeat MRI within two months of reaching that dose and be given the option to continue on hydroxyurea or stop. |
| Healthy Controls | – | Drug: Acetazolamide40 control subjects recruited from first degree relatives of the sickle cell disease population. Diamox (acetazolamide) will be administered during MRI. |
Who may qualify
- Ages
- 7 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- sickle cell disease: non-transfused, simple transfused, exchange transfusion Non-sickle Cell Anemia: Non- transfused and transfused healthy controls
Key inclusion criteria (4 listed)
Key exclusion criteria (7 listed)
- Hospitalization within one month
- Contraindication to acetazolamide use (seizures)
- Severe claustrophobia.
- Pregnancy or nursing (a negative HCG (pregnancy) test must be obtained prior to MRI)
- As a result of medical review, physical examination or screening investigations, the Principal Investigator (PI) considers the subject unfit for the study
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 |
|---|---|---|
| HydroxyureaAlso: Hydreainfo included in arm group | Drug | Anemia Intervention |
| AcetazolamideAlso: DiamoxAcetazolamide will not be considered a treatment; however, it will be used as a tool to help measure cerebralvascular reserve. A dose of 16 mg/kg ACZ will be administered with a maximum of 1400 mg. | Drug | Anemia Intervention, Anemia Observation, Healthy Controls |
Primary outcome
CVR response to transfusion
Time frame: 3-5 days
Cerebral vascular flow reserve will be assessed prior to and following a regularly scheduled blood transfusion
CVR response to hydroxyurea therapy
Time frame: 2-4 months
Change in cerebral vascular reserve at baseline and after initiation of hydroxyurea titrated to maximum tolerated dose
1 secondary outcome
Predictors of CVR response
Time frame: Single study visit
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2024.
- Individual participant dataSharing planned: Undecided
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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.
John C Wood, M.D., PhD principal investigator
CHLA/USC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Thalassemia and Sickle Cell Disease, run by Children's Hospital Los Angeles 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 7 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 30 Oct 2024. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
CVR response to transfusion (time frame: 3-5 days). The study lists 2 primary outcomes in all. 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 30 Oct 2024.