Arginine Therapy for Sickle Cell Disease Pain

NCT02536170 | Completed Phase 2 Results DMC

• 3 other identifiers: IRB00076988FD-R-0048141K24AT009893-01
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 3

Brief Summary

The aim of this study is to determine whether giving extra arginine, a simple amino acid, to patients with sickle cell disease seeking treatment for a pain crisis (vaso-occlusive painful events (VOE) will decrease pain scores, decrease the need for pain medications or decrease length of hospital stay or emergency department visit. Funding Source - FDA OOPD.

Conditions

Sickle Cell Disease; Vaso-occlusive Pain Episode

Keywords

Arginine Therapy

Outcome Measures

Primary Outcomes (1)

• Total Parenteral Opioid Use in IV Morphine Equivalents

  The total amount of parenteral opioids used by participants measured in mg/kg of IV morphine equivalents. The total is calculated after study drug delivery for participants in the emergency department (ED) and during hospital stay.

  Post study drug delivery to discharge from the hospital (Up to 8 days)

Secondary Outcomes (16)

• Length of Hospital Stay

  Discharge (Up to 8 days)

• Time to Vaso-occlusive Pain Event (VOE) Resolution in Emergency Department

  Post study drug delivery (Up to 8 hours)

• Time to Vaso-occlusive Pain Event (VOE) Resolution in Hospital

  Post study drug delivery until discharge (up to 8 days)

• Change in Vaso-occlusive Pain (VOE) Scores

  Baseline, Time of discharge (Up to 8 days)

• Length of Emergency Department (ED) Stay

  Until discharge or Hospital Admission (Up to 24 hours)

Study Arms (3)

L-Arginine

EXPERIMENTAL

Participants will be randomized to receive an intravenous (IV) infusion of L-arginine (100 mg/kg) three times a day until time of discharge from the emergency department (ED) or hospital.

Drug: L-arginine

Loading Dose and L-Arginine

EXPERIMENTAL

Participants will be randomized to receive an intravenous (IV) infusion of one-time loading dose of L-arginine (200 mg/kg) followed by standard dose (100 mg/kg) three times a day until time of discharge from the emergency department (ED) or hospital.

Drug: L-arginine; Drug: L-arginine Loading Dose

Placebo

PLACEBO COMPARATOR

Participants will be randomized to receive an intravenous (IV) infusion of placebo (normal saline 1-2 ml/kg) three times a day until time of discharge from the emergency department (ED) or hospital.

Other: Placebo

Interventions

L-arginine DRUG

L-arginine will be dispensed intravenously (IV) in the standard dose of 100 mg/kg three times a day until discharge from the emergency department (ED) or hospital.

Also known as: Arginine

L-Arginine; Loading Dose and L-Arginine

L-arginine Loading Dose DRUG

One loading dose of L-arginine will be dispensed intravenously (IV) at 200 mg/kg

Also known as: Arginine

Loading Dose and L-Arginine

Placebo OTHER

Placebo of intravenous (IV) normal saline 1-2 ml/kg three times a day until discharge from the emergency department (ED) or hospital.

Placebo

Eligibility Criteria

• Age: 3 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Established diagnosis of sickle cell disease (SCD); all genotypes
• Pain requiring medical care in an acute care setting (such as the emergency department or ED, hospital ward, day hospital, clinic) not attributable to non-sickle cell causes, that is moderate-to-severe requiring parenteral opioids

You may not qualify if:

• Decision to discharge home from the acute care setting
• Hemoglobin less than 5 gm/dL or immediate need for red cell transfusion anticipated within next 12 hours
• Hepatic dysfunction of SGPT greater than 3 times the upper value
• Renal dysfunction of creatinine greater than 1.0
• Mental status or neurological changes
• Acute stroke or clinical concern for stroke
• Pregnancy
• Allergy to arginine
• Two (2) or more ED visits for VOE within the last 7 days prior to CURRENT ED visit
• Hospitalization within 14 days
• Previous randomization in this arginine RCT (patient consented and screen failed before receiving study drug or placebo remains eligible for future participation).
• Use of inhaled nitric oxide, sildenafil or arginine within the last month
• PICU admission from the emergency department
• Hypotension requiring treatment with clinical intervention
• Acidosis with Co2≤ 16

Sponsors & Collaborators

• Emory University: lead
• Children's Healthcare of Atlanta: collaborator
• National Center for Complementary and Integrative Health (NCCIH): collaborator

Study Sites (3)

Children's Healthcare of Atlanta at Hugh Spalding

Atlanta, Georgia, 30303, United States

Location

Children's Healthcare of Atlanta at Egleston

Atlanta, Georgia, 30322, United States

Location

Children's Healthcare of Atlanta at Scottish Rite

Atlanta, Georgia, 30342, United States

Location

Related Publications (4)

• Bakshi N, Liu Z, Gillespie S, Keesari R, Leake D, Khemani K, Kumari P, Rees CA, Dampier C, Morris CR. Patient-reported outcomes in children with sickle cell disease at presentation for an acute pain episode. Blood Adv. 2023 Sep 12;7(17):5103-5107. doi: 10.1182/bloodadvances.2021006794. No abstract available.

  PMID: 36322873 BACKGROUND

• Reyes LZ, Figueroa J, Leake D, Khemani K, Kumari P, Bakshi N, Lane PA, Dampier C, Morris CR. Safety of intravenous arginine therapy in children with sickle cell disease hospitalized for vaso-occlusive pain: A randomized placebo-controlled trial in progress. Am J Hematol. 2022 Jan 1;97(1):E21-E24. doi: 10.1002/ajh.26396. Epub 2021 Nov 12. No abstract available.

  PMID: 34724240 RESULT

• Morris CR, Hatabah D, Korman R, Gillespie S, Bakshi N, Brown LA, Harris F, Leake D, Rees CA, Khemani K, Vichinsky EP, Locke A, Wynn B, Griffiths MA, Wilkinson H, Kumari P, Sudmeier L, Shiva S, Dampier CD. Arginine Therapy for Pain in Sickle Cell Disease: A Phase-2 Randomized, Placebo-Controlled Trial. Am J Hematol. 2025 Jul;100(7):1119-1131. doi: 10.1002/ajh.27692. Epub 2025 Apr 24.

  PMID: 40270092 DERIVED

• Morris CR, Brown LAS, Reynolds M, Dampier CD, Lane PA, Watt A, Kumari P, Harris F, Manoranjithan S, Mendis RD, Figueroa J, Shiva S. Impact of arginine therapy on mitochondrial function in children with sickle cell disease during vaso-occlusive pain. Blood. 2020 Sep 17;136(12):1402-1406. doi: 10.1182/blood.2019003672.

  PMID: 32384147 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Arginine

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential

Results Point of Contact

• Title: Claudia Morris
• Organization: Emory University

claudia.r.morris@emory.edu

404-727-5500

Study Officials

• Claudia Morris, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 27, 2015
• First Posted: August 31, 2015
• Study Start: February 1, 2016
• Primary Completion: February 21, 2021
• Study Completion: February 21, 2021
• Last Updated: September 6, 2023
• Results First Posted: June 6, 2022

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)