What is the mechanism of action of this treatment?

Common treatments for Vaso Occlusive Crisis (VOC) often focus on improving blood flow and alleviating pain. Intravenous L-citrulline, a precursor to L-arginine, increases nitric oxide (NO) production, which is crucial for vasodilation. NO helps relax blood vessels, enhancing blood flow and reducing the occurrence of vaso-occlusive events. This mechanism is vital for VOC patients as it can alleviate pain, reduce opiate usage, and potentially decrease hospital admissions by improving overall vascular health.

What side effects are associated with this type of intervention?

Common treatments for vaso-occlusive crisis (VOC) in sickle cell disease include opioids for pain management, hydration, and blood transfusions. Opioids can cause constipation, nausea, vomiting, drowsiness, and risk of dependency. Hydration therapy is generally safe but can lead to fluid overload. Blood transfusions carry risks of alloimmunization, iron overload, and transfusion reactions. Treatments like intravenous L-citrulline, which increase nitric oxide production, may cause gastrointestinal discomfort, headaches, and potential interactions with other medications affecting nitric oxide pathways.

What prior FDA approvals exist?

The FDA has approved several treatments for Vaso Occlusive Crisis (VOC) in sickle cell disease, focusing on pain management and improving blood flow. Hydroxyurea, an oral medication, has been widely used to reduce the frequency of VOC episodes by increasing fetal hemoglobin levels. More recently, L-glutamine (Endari) was approved to reduce VOC frequency by improving the redox potential in red blood cells. While intravenous L-citrulline, which increases nitric oxide production to improve blood flow, is currently under investigation, no similar nitric oxide precursor treatments have been specifically approved for VOC to date.

What other types of research exist?

Promising novel alternatives to intravenous L-citrulline for treating vaso-occlusive crisis in 2024 include: 1) Voxelotor, which increases hemoglobin's affinity for oxygen, reducing sickling of red blood cells; 2) Crizanlizumab, a monoclonal antibody targeting P-selectin to reduce cell adhesion and vaso-occlusion; and 3) Gene therapies like LentiGlobin, which aim to correct the genetic defect causing sickle cell disease. These treatments have shown potential in clinical trials to improve outcomes for VOC patients.

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Amino Acid

L-citrulline for Sickle Cell Anemia

Phase 1 & 2

Waitlist Available

Research Sponsored by Asklepion Pharmaceuticals, LLC

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be younger than 65 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up collected from enrollment to end of study over 18 months

Summary

This trial is testing a treatment called L-citrulline for children and young adults with sickle cell disease who are having severe pain episodes. The treatment aims to improve blood flow and reduce pain by relaxing blood vessels. Researchers hope this will decrease the need for strong painkillers and hospital stays.

Who is the study for?

This trial is for children and young adults aged 6-21 with sickle cell disease experiencing a vaso-occlusive crisis. Participants must not be in any other clinical trials for sickle cell treatments within the last 3 months, have severe anemia, or recent blood transfusions. Females of childbearing age should test negative for pregnancy and use contraception.

What is being tested?

The study tests if L-citrulline injections can help manage pain during a vaso-occlusive crisis in sickle cell patients, potentially reducing opiate use and hospital stays. It's a two-part trial; Part 1 determines the best dose, while Part 2 uses that dose to compare against placebo in more subjects.

What are the potential side effects?

Potential side effects of L-citrulline may include digestive issues like nausea or stomach pain, allergic reactions for those sensitive to the drug, changes in blood pressure or heart rate, headaches, or dizziness.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ collected from enrollment to end of study over 18 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~collected from enrollment to end of study over 18 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and collected from enrollment to end of study over 18 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Assessment of safety

Change from baseline in amount of overall opioid use

Change in Visual Analogue Scale (VAS) pain score

+3 more

Secondary study objectives

Duration or length of hospital stay

Preliminary assessment of change of opioid use overall

Preliminary assessment of pain change measured

+1 more

Trial Design

6Treatment groups

Active Control

Placebo Group

Group I: Arm 1 (L-citrulline)Active Control1 Intervention

25 mg/kg bolus + 9 mg/kg/hr continuous infusion of L-citrulline for up to 7 hours

Group II: Arm 2 (L-citrulline)Active Control1 Intervention

50 mg/kg bolus + 9 mg/kg/hr continuous infusion of L-citrulline for up to 7 hours

Group III: Arm 4 (L-citrulline)Active Control1 Intervention

100 mg/kg bolus + 11 mg/kg/hr continuous infusion of L-citrulline for up to 7 hours

Group IV: Part 2 Arm 1 (L-citrulline)Active Control1 Intervention

Subjects will be randomized to 2 of the doses selected from Part 1 and placebo in a 1:1:1 ratio. L-citrulline will be administered to the active arm.

Group V: Arm 3 (L-citrulline)Active Control1 Intervention

100 mg/kg bolus + 9 mg/kg/hr continuous infusion of L-citrulline for up to 7 hours

Group VI: Part 2 Arm 2 D5 1/2NSPlacebo Group1 Intervention

Subjects will be randomized to 2 of the doses selected from Part 1 and placebo in a 1:1:1 ratio.

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Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Vaso Occlusive Crisis (VOC) often focus on improving blood flow and alleviating pain. Intravenous L-citrulline, a precursor to L-arginine, increases nitric oxide (NO) production, which is crucial for vasodilation. NO helps relax blood vessels, enhancing blood flow and reducing the occurrence of vaso-occlusive events. This mechanism is vital for VOC patients as it can alleviate pain, reduce opiate usage, and potentially decrease hospital admissions by improving overall vascular health.