Arginine Therapy for Sickle Cell Disease

(STArT Trial)

No longer recruiting at 11 trial locations

Overseen By Claudia Morris, MD

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Emory University

Must not be taking: Ketamine, Glutamine, others

Disqualifiers: Stroke, Pregnancy, Hypotension, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1-2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests an IV treatment called arginine hydrochloride to determine its effectiveness in helping children with sickle cell disease during painful episodes. Researchers aim to assess the safety and efficacy of this treatment for pain relief. Participants will receive either the arginine treatment or a placebo, a harmless substance resembling the treatment. Children with sickle cell disease who require strong pain relief in a medical setting may be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you've used certain drugs like glutamine in the last 30 days or new sickle cell drugs in the last 3 months.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Previous studies have shown that arginine is safe for treating sickle cell disease (SCD). Research suggests that arginine can help reduce pain and might decrease the need for pain medication. It is considered a safe nutritional supplement, especially for children during painful episodes. Some studies also found that it can improve certain blood tests and protect the liver. Overall, arginine appears well-tolerated, with no major safety concerns reported for those with SCD. ^{1 2 3 4 5}

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

Unlike the standard treatments for sickle cell disease, which often focus on managing pain and preventing complications, arginine hydrochloride offers a unique approach by potentially enhancing nitric oxide production. This increased nitric oxide can help dilate blood vessels, improving blood flow and reducing the sickling of red blood cells. Researchers are excited about arginine hydrochloride because it targets the root cause of the disease’s symptoms rather than just the symptoms themselves, offering hope for a more effective and comprehensive treatment option.

What evidence suggests that arginine hydrochloride might be an effective treatment for sickle cell disease?

Research has shown that L-arginine hydrochloride, which participants in this trial may receive, might benefit people with sickle cell disease. Studies indicate it can increase hemoglobin F, improving blood flow and reducing pain during sickle cell crises. One study found that arginine lessened the need for pain medications, a significant benefit for those experiencing painful episodes. Arginine likely works by boosting nitric oxide levels, relaxing blood vessels, and improving circulation. These encouraging findings suggest that arginine could complement current treatments for sickle cell disease. ^{2 5 6 7 8}

Who Is on the Research Team?

Claudia Morris, MD

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

The STArT trial is for children and young adults aged 3-21 with sickle cell disease experiencing pain episodes needing medical care. They must not have had certain treatments or hospitalizations recently, be stable without severe anemia, and able to understand English or Spanish.

Inclusion Criteria

I have been diagnosed with sickle cell disease.

I have had severe pain from sickle cell disease treated with strong painkillers.

I am between 3 and 21 years old.

Exclusion Criteria

I am 18 or older but cannot make medical decisions for myself.

Previous randomization in this arginine phase 3 RCT; OR

pregnancy; OR

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive up to 21 doses of IV arginine or placebo over 7 to 8 days

1-2 weeks

Daily visits for IV administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Regular follow-up visits

Long-term Follow-up

Participants are followed for up to 28 days following hospital discharge to assess long-term outcomes

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Arginine Hydrochloride

Trial Overview This study tests IV arginine therapy versus saline (a placebo) in managing pain during vaso-occlusive episodes in sickle cell patients. It aims to determine the effectiveness and safety of arginine compared to a standard treatment.

How Is the Trial Designed?

Group I: L-Arginine Hydrochloride Experimental Treatment 1 Intervention

Participants receiving L-arginine hydrochloride in parenteral form. Participants receive up to 21 doses, with participants who are discharged early receiving fewer doses.

Group II: Placebo Placebo Group 1 Intervention

Participants receiving normal saline as a placebo for L-arginine hydrochloride for up to 21 doses, with participants who are discharged early receiving fewer doses.

Arginine Hydrochloride is already approved in European Union, United States for the following indications:

Approved in European Union as L-arginine for:

• Nutritional supplement
• COVID-19-related conditions

Approved in United States as L-arginine for:

• Nutritional supplement
• COVID-19-related conditions

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

Claudia R. Morris

Lead Sponsor

Trials

1

Recruited

360+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10090802/

Effects of l‐arginine supplementation in patients with sickle ... Our meta‐analysis showed that l‐arginine use for SCD could be beneficial, increase hemoglobin F and exert blood pressure‐lowering and hepatoprotective ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3762093/

A randomized, placebo-controlled trial of arginine therapy ... Arginine is a safe and inexpensive intervention with narcotic-sparing effects that may be a beneficial adjunct to standard therapy for sickle cell-related pain ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04839354

Sickle Cell Disease Treatment With Arginine Therapy ... The trial is designed to test intravenous (IV) arginine therapy in children with sickle cell disease (SCD) and vaso-occlusive painful episodes (VOE)

4. pecarn.org pecarn.org/pecarn_news/start-study-arginine-and-sickle-cell-crisis/

STArT Study: Arginine and sickle cell crisis - PECARN Studies have shown that decreased bioavailability of the amino acid L-arginine is associated with sickle cell disease.

5. trialsjournal.biomedcentral.com trialsjournal.biomedcentral.com/articles/10.1186/s13063-023-07538-z

Sickle Cell Disease Treatment with Arginine Therapy (STArT) The primary aim of the STArT trial is to determine the efficacy of intravenous arginine therapy to reduce time to crisis resolution, in children ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40526198/

Clinical Study to Evaluate the Possible Efficacy and Safety ... Conclusions: L-arginine is associated with a reduction in TRJV, NT-proBNP, and improvements in NO biomarkers, suggesting it may be beneficial ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04839354

Sickle Cell Disease Treatment With Arginine Therapy ... Children may therefore be more responsive to arginine therapy during an acute pain event compared to adults. Arginine is a safe nutritional supplement that is ...

8. haematologica.org haematologica.org/article/view/6774

A randomized, placebo-controlled trial of arginine therapy ... Arginine is a safe and inexpensive intervention with narcotic-sparing effects that may be a beneficial adjunct to standard therapy for sickle ...