L-Citrulline for Sickle Cell Disease

Not yet recruiting at 6 trial locations

Overseen By Gurdyal Kalsi, MD, MFPM (Hon)

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Asklepion Pharmaceuticals, LLC

Must not be taking: Steroids, Nitrates, Sildenafil, others

Disqualifiers: Sepsis, Stroke, Severe anemia, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for pain episodes in children, teens, and young adults with sickle cell disease. The study aims to determine if L-citrulline, a naturally occurring amino acid, can reduce pain during these sudden episodes. Participants will receive either L-citrulline or a placebo (a look-alike with no active ingredients) through an IV, alongside their usual pain treatments. Young people with sickle cell disease who experience painful episodes and have no other major health issues may be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Do I have to stop taking my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but the doctor will explain any restrictions during the consent process. Some medications, like systemic steroids or certain blood pressure drugs, are not allowed if taken recently.

Is there any evidence suggesting that L-citrulline is likely to be safe for humans?

Research has shown that administering L-citrulline through an IV is generally safe for people with sickle cell disease. In one study, patients experienced no serious side effects, with mild drowsiness being the most common issue. Importantly, the treatment caused no harmful effects. This suggests that IV-administered L-citrulline could be a promising option for treating pain episodes in sickle cell disease. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sickle cell disease?

Most treatments for sickle cell disease focus on managing pain through opioids or other pain medications. However, L-citrulline is unique because it is a naturally occurring amino acid that targets vaso-occlusive crises, a primary complication of sickle cell disease. Unlike standard pain management methods, L-citrulline is administered intravenously and works by potentially improving blood flow, reducing the frequency and severity of these crises. Researchers are excited because this treatment could offer a more targeted approach with possibly fewer side effects compared to traditional pain medications.

What evidence suggests that L-citrulline might be an effective treatment for sickle cell disease?

Research has shown that L-citrulline might help treat painful episodes in sickle cell disease, known as vaso-occlusive crises (VOCs). In this trial, participants in the L-citrulline intravenous treatment arm will receive L-citrulline through an IV, which studies suggest may help reduce pain during these episodes. Early findings indicate it improves blood flow, potentially easing pain and discomfort during a VOC. A review noted that L-citrulline is generally safe for people with sickle cell disease and might help reduce oxidative stress, a condition that can exacerbate pain. While more research is needed, these early results are promising for those experiencing VOCs. ^{1 2 3 5 6}

Who Is on the Research Team?

Suvankar Majumdar, MD

Principal Investigator

Center for Cancer and Blood Disorders, Children's National Hospital

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 6-21 with Sickle Cell Disease experiencing a pain episode known as vaso-occlusive crisis. They must be able to give consent or have a guardian who can, and should not be taking any medications that are disallowed in the study.

Inclusion Criteria

Patients or parents or legal guardian of the patient who are willing and able to sign and provide consent and assent (where appropriate for the age of the child)

I am between 6 and 21 years old.

My condition is stable and I have no acute issues except for pain crises due to sickle cell.

Exclusion Criteria

I haven't used medications like nitrates or sildenafil in the last 30 days.

I am unable to give consent due to my age.

History of allergic reaction to L-citrulline product or dextrose

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Treatment

Participants receive either L-citrulline or placebo intravenously, with a bolus dose followed by a continuous infusion for up to 12 hours

1 day

In-patient hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up calls around Day 2, Day 7, and Day 30

30 days

3 follow-up calls

What Are the Treatments Tested in This Trial?

Interventions

• L-citrulline

Trial Overview The trial tests if L-citrulline, an IV-administered drug, can reduce pain during sickle cell crises compared to a placebo. Participants will also receive standard pain treatments and are randomly assigned to either the drug or placebo group.

How Is the Trial Designed?

Group I: L-citrulline Intravenous Treatment Arm Experimental Treatment 1 Intervention

Participants randomized to this arm will receive intravenous (IV) L-citrulline, a naturally occurring amino acid being investigated for its potential to treat vaso-occlusive crises (VOCs) in sickle cell disease. The study drug will be administered as a 50 mg/kg IV bolus, followed by a continuous infusion at 9 mg/kg/hour for up to 12 hours. The investigational product is provided as an isotonic solution in vials containing L-citrulline 50 mg/mL. Treatment will begin within 120 minutes of informed consent/assent and following the initial dose of opioid or ketamine, but prior to any subsequent doses. All participants will continue to receive standard-of-care (SoC) pain management per site protocol, which may be adjusted based on clinical response to study treatment.

Group II: Placebo Placebo Group 1 Intervention

Participants randomized to this arm will receive a placebo intravenous (IV) treatment designed to match the appearance and administration schedule of L-citrulline. The placebo will be given as a single bolus dose followed by a continuous infusion for up to 12 hours. All participants will continue to receive standard of care pain management for sickle cell disease, consistent with the treating site's protocol and adjusted as needed based on the patient's clinical condition.

Who Is Running the Clinical Trial?

Asklepion Pharmaceuticals, LLC

Lead Sponsor

Trials

6

Recruited

450+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06989567

A Study of Intravenous L-Citrulline in Patients Aged 6-21 ... This study is testing whether L-citrulline, given through an IV, can help treat a pain crisis (VOC) in people with sickle cell disease (SCD) more quickly and ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9868327/

Design of an adaptive randomized clinical trial ... The study will evaluate efficacy and tolerability of incremental doses of intravenous (IV) l-citrulline in patients with SCD while receiving standard of care ...

3. trialx.com trialx.com/clinical-trials/listings/296609/intravenous-l-citrulline-for-vaso-occlusive-pain-episode-in-sickle-cell-disease/

Intravenous L-Citrulline for Vaso-occlusive Pain Episode in ... The goal of this clinical trial is to learn if intravenous citrulline works to treat acute pain in hospitalized patients with sickle cell ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04852172

L-citrulline Injection in Patients Aged 6-21 Years Old with ... The purpose of this study is to determine if intravenous L-citrulline can abrogate an active vaso-occlusive crisis in sickle cell disease, resulting in ...

5. authorea.com authorea.com/doi/pdf/10.22541/au.175404797.70233011

Systematic Review of L-Citrulline Supplementation Effect in ... Our systematic review showed that oral L-Citrulline supplementation is safe in patients with SCD and could be beneficial in decreasing oxidative ...

6. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/bjh.15124

A phase 1 dose‐finding study of intravenous L‐citrulline ... Overall, intravenous citrulline in SCD was well tolerated and safe. There were no AEs ≥ grade 2 level of toxicity. Drowsiness was ...