Cerebrovascular Reserve and White Matter Disease in Patients with Chronic Anemia

NCT03715972 | Completed DMC

• 2 other identifiers: CHLA-17-004961R01HL136484-01A1
• Study Type: observational
• Target: 165
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Thalassemia; Sickle Cell Disease; Healthy Controls

Keywords

cerebrovascular reserve; white matter disease in patients with chronic anemia

Outcome Measures

Primary Outcomes (2)

• CVR response to transfusion

  Cerebral vascular flow reserve will be assessed prior to and following a regularly scheduled blood transfusion

  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

  2-4 months

Secondary Outcomes (1)

• Predictors of CVR response

  Single study visit

Study Arms (3)

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.

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.

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.

Drug: Acetazolamide

Interventions

Hydroxyurea DRUG

info included in arm group

Also known as: Hydrea

Anemia Intervention

Acetazolamide DRUG

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.

Also known as: Diamox

Anemia Intervention; Anemia Observation; Healthy Controls

Eligibility Criteria

• Age: 7 Years+
• Gender Eligibility Details: for healthy controls we will try to match gender to those that have been enrolled under the anemia cohort
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

sickle cell disease: non-transfused, simple transfused, exchange transfusion Non-sickle Cell Anemia: Non- transfused and transfused healthy controls

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Children's Hospital Los Angeles: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): collaborator
• Vanderbilt University Medical Center: collaborator

Study Sites (1)

CHLA

Los Angeles, California, 90027, United States

Location

MeSH Terms

Conditions

Thalassemia; Anemia, Sickle Cell

Interventions

Hydroxyurea; Acetazolamide

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

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals; Thiadiazoles; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• John C Wood, M.D., PhD

  CHLA/USC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics and Radiology

Study Record Dates

• First Submitted: February 20, 2018
• First Posted: October 23, 2018
• Study Start: July 15, 2018
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: October 30, 2024

Record last verified: 2023-05

Locations

US (1)