Carbon Dioxide for Sickle Cell Anemia

Recruiting at 1 trial location

Overseen By Kristin P Guilliams, MD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Washington University School of Medicine

Must not be taking: Vasodilators

Disqualifiers: Pregnancy, Epilepsy, Stroke, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how blood flow and metabolism affect brain development in young people with sickle cell anemia (SCA) and healthy individuals. Researchers will use MRI scans to study how well the brain's blood vessels expand when participants breathe in carbon dioxide (CO2), assessing the brain's response to increased oxygen demands. Participants with SCA may face brain growth challenges due to reduced oxygen supply, and this trial seeks to explore these effects. Children and young adults aged 4-21 with sickle cell anemia, who can undergo an MRI without sedation and are not on certain medications, might be suitable for this trial. As an unphased trial, this study offers participants the chance to contribute to important research that could enhance understanding and treatment of sickle cell anemia.

Will I have to stop taking my current medications?

The trial requires that participants are not taking vasodilatory medications (drugs that widen blood vessels), such as sildenafil or verapamil. If you are on these medications, you may need to stop taking them to participate.

What prior data suggests that this method is safe for studying brain blood flow and metabolism?

Research shows that using carbon dioxide to test blood flow in the brains of people with sickle cell anemia is generally safe. Studies have found that carbon dioxide can help blood vessels in the brain widen, which is crucial for delivering oxygen. In this context, carbon dioxide serves as a tool to assess blood vessel function, not as a medicine. Most participants tolerate this procedure well.

There is no evidence of significant harmful effects when using carbon dioxide in this manner. However, people with sickle cell disease might experience a slower reaction to carbon dioxide, causing their blood vessels to widen more slowly. This slower response is not harmful, but researchers monitor it closely. Overall, research suggests that using carbon dioxide in these tests is safe and provides valuable information about brain health in sickle cell patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using carbon dioxide for sickle cell anemia because it offers a novel approach compared to existing treatments. Most current therapies focus on managing symptoms or preventing complications, such as using hydroxyurea to increase fetal hemoglobin or blood transfusions to reduce sickle cell crisis frequency. However, carbon dioxide could work differently by potentially influencing blood flow or oxygen delivery in a way that directly addresses the underlying blood cell deformities. This approach might provide a new avenue for improving patient outcomes and quality of life.

What evidence suggests that carbon dioxide might be an effective treatment for sickle cell anemia?

This trial will investigate the effects of carbon dioxide on sickle cell anemia. Research has shown that increasing carbon dioxide levels in the blood can reduce the sickling of red blood cells in individuals with sickle cell anemia, potentially improving blood flow and lowering stroke risk. Studies indicate that carbon dioxide can widen blood vessels in the brain, increasing blood flow without increasing brain activity. This is crucial because people with sickle cell disease often have blood vessels that do not respond well to changes in carbon dioxide. By helping blood vessels expand, carbon dioxide might facilitate oxygen delivery to the brain, potentially reducing stroke risk and supporting better brain development. ^{1 2 3 5 6}

Who Is on the Research Team?

Kristin P Guilliams, MD

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 4-21 with sickle cell anemia (SCA) or healthy individuals without significant psychiatric history, epilepsy, stroke, or cerebrovascular disease. Participants must be able to have an MRI scan without sedation and not be pregnant.

Inclusion Criteria

I have sickle cell disease (Hb SS) or Sickle Beta-thalassemia.

I am not taking any blood pressure-lowering medications like sildenafil or verapamil.

I am between 4 and 21 years old.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo initial MRI scans, blood draw, and cognitive assessments

1-2 weeks

1 visit (in-person)

Cerebrovascular Reactivity Testing

Participants undergo MRI to measure blood flow changes in response to carbon dioxide

15 minutes

1 visit (in-person)

Follow-up

Participants are monitored for changes in brain volume and cortical thickness over time

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Carbon Dioxide

Trial Overview The study tests how breathing in carbon dioxide affects blood flow in the brain using MRI scans. It aims to understand blood vessel function related to oxygen delivery during normal activities and stress in SCA patients compared to healthy controls.

How Is the Trial Designed?

Group I: Sickle Cell Anemia Active Control 1 Intervention

Group II: Healthy Control Active Control 1 Intervention

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Published Research Related to This Trial

In a study involving sickle cell disease patients, administering carbon monoxide at concentrations of 1000-2000 ppm led to a significant prolongation of red blood cell survival, indicating a potential positive effect on the properties of sickle cells.

Despite these promising results, the authors do not recommend carbon monoxide as a treatment for sickle cell disease at this time, but suggest that further controlled trials could be beneficial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of carbon monoxide on red cell life span in sickle cell disease. Beutler, E.[2021]

A semiautomated extracorporeal treatment using cyanate for four patients with sickle cell anemia resulted in significant hemoglobin carbamylation without serious toxicity, indicating a safer method of administration compared to systemic delivery.

Two out of four patients showed a hematologic response, suggesting potential efficacy of this treatment approach, but further research is needed to fully assess its effectiveness in managing sickle cell anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary studies of continuous extracorporeal carbamylation in the treatment of sickle cell anemia. Balcerzak, SP., Grever, MR., Sing, DE., et al.[2007]

A study involving 21 Nigerians with homozygous sickle-cell disease found that their ventilatory response to carbon dioxide is similar to that of healthy individuals, indicating normal sensitivity to carbon dioxide levels.

The research utilized a rebreathing technique to measure this response, suggesting that sickle-cell patients can effectively regulate their breathing in response to carbon dioxide, which is important for their respiratory health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ventilatory response to carbon dioxide in patients with homozygous sickle-cell disease. Elegbeleye, OO., Akinsete, FI., Afonja, AO., et al.[2019]

Inhibition of carbonic anhydrase (CA) activity using acetazolamide (AZ) significantly affects hemoglobin's (Hb) affinity for oxygen, as shown by changes in the oxygen partial pressure at 50% saturation (P(50)) in human blood.

The study found that the effects of CA inhibition on Hb-oxygen affinity were temporary and diminished after 4 hours of tonometry, suggesting that CA plays a crucial role in regulating oxygen transport by influencing CO(2) movement between air and liquid compartments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regulation of hemoglobin affinity for oxygen by carbonic anhydrase. Gai, X., Taki, K., Kato, H., et al.[2013]

The quality of life for patients with sickle cell disease has significantly improved in developed countries over the last 20 years due to various preventive measures and treatments.

Individualized therapy is becoming more important, as genetic studies are helping to link specific genetic variations to treatment responses, which could enhance efficacy and reduce side effects for sickle cell patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The genomics of new drugs in sickle cell disease. Makis, AC., Hatzimichael, EC., Stebbing, J.[2018]

In sickle cell anemia (SS), increasing levels of carbon dioxide (PCO2) can inhibit the sickling of red blood cells, particularly at higher pH levels, suggesting a potential therapeutic role for managing PCO2 in patients.

The study found that SS blood exhibits unique responses to changes in PCO2, including increased oxygen affinity and significant differences in the Bohr effect compared to normal blood (AA), indicating that CO2 levels can significantly impact respiratory functions and red blood cell properties in sickle cell disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of carbon dioxide and pH variations in vitro on blood respiratory functions, red blood cell volume, transmembrane pH gradients, and sickling in sickle cell anemia. Ueda, Y., Bookchin, RM.[2014]

In a study involving eight patients with sickle cell anemia, extracorporeal carbamylation of red blood cells led to significant improvements in hematologic parameters, including an increase in hemoglobin levels from 6.4 to 9.1 g/100 ml and a 65% reduction in irreversibly sickled erythrocytes over three months.

The treatment also resulted in an 80% decrease in the frequency of severe painful crises, with spontaneous crises virtually disappearing, indicating a promising therapeutic effect without noted toxic side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematologic and clinical responses in patients with sickle cell anemia after chronic extracorporeal red cell carbamylation. Deiderich, DA., Trueworthy, RC., Gill, P., et al.[2018]

Citations

1. withpower.com withpower.com/trial/phase-anemia-sickle-cell-5-2021-586a0

Carbon Dioxide for Sickle Cell Anemia Research suggests that increasing carbon dioxide levels in the blood might help reduce the sickling of red blood cells in sickle cell anemia, potentially ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9437621/

Sickle cell cerebrovascular reactivity to a CO2 stimulus These findings show that CVR represents a promising tool to assess disease state, stroke risk, and therapeutic efficacy of treatments in SCD and merits further ...

3. researchgate.net researchgate.net/publication/318851751_Plasma_Carbonic_Anhydrase_II_Level_is_Increased_in_Children_with_Sickle_Cell_Anaemia_Compared_to_Healthy_Controls

(PDF) Plasma Carbonic Anhydrase II Level is Increased in ... Conclusions: These findings suggest that omega-3 fatty acids can be an effective, safe, and affordable therapy for sickle cell anemia. View ...

4. jscimedcentral.com jscimedcentral.com/jounal-article-info/Archives-of-Paediatric-%26-Developmental-Pathology/Plasma-Carbonic-Anhydrase-II--Level-is-Increased-in-Children-with-Sickle-Cell-Anaemia-Compared-to-Healthy-Controls-9532

Plasma Carbonic Anhydrase II Level is Increased in ... Result: The mean carbonic anhydrase levels were significantly elevated in children who suffered from sickle cell disease compared to healthy controls (p=0.0001) ...

5. rarediseaseadvisor.com rarediseaseadvisor.com/news/cerebrovascular-response-co2-reduced-patients-sickle-cell-disease/

Cerebrovascular Response to CO2 Decreased in Patients ... A study has found that patients with sickle cell disease have a decreased and slowed response to carbon dioxide.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40485583/

Annual PM2.5 exposure and clinical, laboratory, and stroke ... Annual PM2.5 exposure and clinical, laboratory, and stroke-risk outcomes in pediatric sickle cell disease. JCI Insight. 2025 Jun ...