21 Participants Needed

Arginine Therapy for Sickle Cell Disease

(R34 pK/PD Trial)

Recruiting at 1 trial location
RM
CM
Overseen ByClaudia Morris, MD
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Approved in 3 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine whether giving extra arginine to patients with sickle cell disease seeking treatment for vaso-occlusive painful events (VOE) will decrease pain scores, decrease need for pain medications or decrease length of hospital stay or emergency department visit.

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 inhaled nitric oxide, sildenafil, or arginine in the last 14 days.

What data supports the effectiveness of this drug for sickle cell disease?

Research suggests that L-arginine supplementation can increase nitric oxide production during vaso-occlusive crises in sickle cell disease, potentially improving symptoms. Additionally, L-arginine has shown promise in reducing pulmonary hypertension, a serious complication of sickle cell disease, by lowering pulmonary artery pressure.12345

Is arginine therapy safe for humans?

Arginine supplementation is generally considered safe for humans, with an observed safe level of about 20 grams per day. It has been used safely in vulnerable groups like pregnant women and preterm infants, and animal studies show no adverse effects with high doses. However, more research is needed to fully confirm its safety in humans.678910

How does the drug arginine differ from other treatments for sickle cell disease?

Arginine is unique because it helps improve blood flow and reduce complications in sickle cell disease by increasing nitric oxide levels, which protect blood vessels and reduce inflammation. This mechanism is different from other treatments that may not target these specific pathways.124811

Research Team

Claudia R. Morris | Faculty | People ...

Claudia Morris, MD

Principal Investigator

Emory University

Eligibility Criteria

This trial is for children and young adults aged 7-21 with Sickle Cell Disease (specifically Hemoglobin SS or Sβᴼ-thalassemia), weighing at least 55lbs, who are experiencing pain that requires strong painkillers. They must not be pregnant, have had a recent hospitalization, severe liver or kidney issues, certain other types of sickle cell disease, or an allergy to arginine.

Inclusion Criteria

I have been diagnosed with sickle cell disease, either Hb-SS or Sβᴼ-thalassemia.
I am between 7 and 21 years old.
I have pain from sickle cell that needed strong painkillers in a hospital or clinic.
See 1 more

Exclusion Criteria

Hemoglobin less than 5 gm/dL
You are allergic to arginine.
I expect to need a blood transfusion soon.
See 10 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive intravenous arginine therapy for vaso-occlusive painful events in sickle cell disease

Up to 7 days
Daily visits for intravenous administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • Arginine
Trial OverviewThe study tests if extra arginine can help reduce pain levels in patients with sickle cell disease during painful episodes. It looks at whether this treatment can lessen the need for pain medication or shorten the time spent in hospitals or emergency departments.
Participant Groups
6Treatment groups
Experimental Treatment
Group I: Standard doseExperimental Treatment1 Intervention
Subjects with sickle cell disease (SCD) and vaso-occlusive painful events (VOE) will be randomized to receive an intravenous (IV) infusion of a standard dose of arginine (100 mg/kg) three times a day for seven days or until discharged from the hospital, whichever occurs first
Group II: Non-Randomized Loading dose 500 mg/kg + standard doseExperimental Treatment1 Intervention
Arginine will be dispensed intravenously (in the vein) as an initial bolus (loading) arginine dose at 500 mg/kg once, followed by a standard dose of 100mg/kg every 8 hours until discharge or for a total of 21 doses of arginine, whichever comes first.
Group III: Non-Randomized Loading dose 400mg/kg + standard doseExperimental Treatment1 Intervention
Arginine will be dispensed intravenously (in the vein) as an initial bolus (loading) arginine dose at 400 mg/kg once, followed by a standard dose of 100mg/kg every 8 hours until discharge or for a total of 21 doses of arginine, whichever comes first.
Group IV: Non-Randomized Loading dose 300 mg/kg + standard doseExperimental Treatment1 Intervention
Arginine will be dispensed intravenously (in the vein) as an initial bolus (loading) arginine dose at 300 mg/kg once, followed by a standard dose of 100mg/kg every 8 hours until discharge or for a total of 21 doses of arginine, whichever comes first.
Group V: Loading dose + standard doseExperimental Treatment2 Interventions
Subjects with sickle cell disease and vaso-occlusive painful events (VOE) will be randomized to receive an intravenous (IV) infusion of an initial loading dose of arginine (200 mg/kg) given over 30 minutes and then receive an intravenous (IV) infusion of a standard dose of arginine (100 mg/kg) three times a day for seven days or until discharged from the hospital, whichever occurs first
Group VI: Loading dose + continuous infusionExperimental Treatment2 Interventions
Subjects with sickle cell disease and vaso-occlusive painful events (VOE) will be randomized to receive an intravenous (IV) infusion of an initial loading dose of arginine (200 mg/kg) given over 30 minutes and then receive a continuous intravenous (IV) infusion of 300 mg/kg/24hr for 7 days or until discharged from the hospital, whichever occurs first

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

🇺🇸
Approved in United States as L-arginine for:
  • Dietary supplementation
  • Angina
  • Erectile dysfunction
  • High blood pressure
🇪🇺
Approved in European Union as L-arginine for:
  • Dietary supplementation
  • Angina
  • Erectile dysfunction
  • High blood pressure
🇨🇦
Approved in Canada as L-arginine for:
  • Dietary supplementation
  • Angina
  • Erectile dysfunction
  • High blood pressure

Find a Clinic Near You

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials
1,735
Recruited
2,605,000+

National Center for Complementary and Integrative Health (NCCIH)

Collaborator

Trials
886
Recruited
677,000+

Children's Healthcare of Atlanta

Collaborator

Trials
172
Recruited
108,000+

Findings from Research

Patients with sickle cell disease (SSD) had significantly lower levels of L-arginine compared to healthy controls, which may contribute to immune dysfunction.
Supplementing with L-arginine improved lymphocyte blastogenesis in response to phytohemagglutinin (PHA) for both SSD patients and controls, but did not enhance responses to specific antigens like candida, indicating a selective effect on immune activation.
Effect of L-arginine supplementation on immune responsiveness in patients with sickle cell disease.Scavella, A., Leiva, L., Monjure, H., et al.[2017]
In a pilot Phase II clinical trial involving five patients with sickle cell disease, oral L-citrulline supplementation significantly improved well-being, increased plasma arginine levels, and reduced high leukocyte and neutrophil counts, suggesting a potential therapeutic benefit.
No side effects or toxicity were reported from L-citrulline, indicating it may be a safe option for palliative therapy in sickle cell disease, warranting further placebo-controlled, long-term studies.
Oral citrulline as arginine precursor may be beneficial in sickle cell disease: early phase two results.Waugh, WH., Daeschner, CW., Files, BA., et al.[2018]
In a study of 10 patients with sickle cell disease, oral arginine therapy led to a significant 15.2% reduction in pulmonary artery systolic pressure after just 5 days, suggesting it may effectively lower pulmonary hypertension associated with the disease.
Elevated arginase activity in these patients may limit the availability of arginine, which is crucial for nitric oxide production, indicating that arginine therapy could help counteract this deficiency and improve patient outcomes.
Arginine therapy: a new treatment for pulmonary hypertension in sickle cell disease?Morris, CR., Morris, SM., Hagar, W., et al.[2022]

References

Effect of L-arginine supplementation on immune responsiveness in patients with sickle cell disease. [2017]
Oral citrulline as arginine precursor may be beneficial in sickle cell disease: early phase two results. [2018]
Arginine therapy: a new treatment for pulmonary hypertension in sickle cell disease? [2022]
Effects of l-arginine supplementation in patients with sickle cell disease: A systematic review and meta-analysis of clinical trials. [2023]
Arginine therapy: a novel strategy to induce nitric oxide production in sickle cell disease. [2019]
Catabolism and safety of supplemental L-arginine in animals. [2018]
Assessment of the application for renewal of authorisation of l-arginine produced by fermentation using Corynebacterium glutamicum NITE SD 00285 for all animal species. [2020]
Arginine metabolism and nutrition in growth, health and disease. [2023]
The metabolic basis of arginine nutrition and pharmacotherapy. [2019]
10.United Statespubmed.ncbi.nlm.nih.gov
Safety and Effectiveness of Arginine in Adults. [2023]
[Arginine--metabolism and functions in the human organism]. [2016]