NCT05018728

The Effect of Voxelotor on Cerebral Hemodynamic Response in Children With Sickle Cell Anemia

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 22 (actual)
• Sponsor: Emory University · Academic / Other
• Sex: All
• Age: 4 Years – 30 Years
• Healthy volunteers: Not accepted

Summary

Voxelotor is a new drug for adolescents and adults with sickle cell disease that improves hemoglobin levels and reduces the incidence of worsening anemia. However, it is unclear whether this increase in hemoglobin is associated with a reduction in cerebral metabolic stress. This study will measure the effects of voxelotor on cerebral hemodynamics.

Detailed description

Sickle cell disease (SCD) is a genetic blood disorder that has profound effects on the brain. In the presence of chronic anemia, the brain microvasculature dilates in order to maintain adequate oxygen delivery to the tissue. As cerebral blood flow increases and the vasculature becomes maximally dilated, oxygen extraction fraction (OEF) increases to keep up with metabolic demand. Unfortunately, this state of maximized response leaves the brain vulnerable and ill-equipped to adapt to increased metabolic demand; consequently, the tissue is susceptible to infarction when blood flow/volume are insufficient to maintain sufficient oxygen metabolism. Voxelotor is a first-in-class drug approved by the FDA for treatment of adults and children (aged four years and older) with SCD. This study will examine the effects of voxelotor on cerebral hemodynamics. The researchers hypothesize that as hemoglobin increases due to voxelotor, cerebral blood flow and oxygen extraction fraction will decrease. To test this hypothesis, measurements of brain blood flow, oxygen extraction, and oxygen metabolism will be made using a customized diffuse correlation spectroscopy and frequency domain near-infrared spectroscopy system (DCS/fdNIRS). This non-invasive, optical technique uses light to estimate an average oxygen saturation of the microvasculature, i.e., capillaries, arterioles, and venules. All participants will receive voxelotor, administered orally once daily as tablets, dispersible tablets or as powder for oral suspension at a dose based on their body weight, for 12 weeks. Measurements of cerebral blood flow, oxygen extraction, and oxygen metabolism will be made at baseline (before starting drug), and at 4, and 12 weeks after the start of voxelotor.

Conditions

• Sickle Cell Anemia in Children

Interventions

Type	Name	Description
DRUG	Voxelotor	Voxelotor is taken orally once a day. Participants 12 years or older will take 1500 mg/day. Participants younger than 12 years of age will receive a dose based on their body weight to provide exposure corresponding to the adult dose of 1500 mg/day.

Timeline

• Start date: 2022-03-28
• Primary completion: 2024-10-22
• Completion: 2024-10-22
• First posted: 2021-08-24
• Last updated: 2025-12-12

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study