Arginine Therapy for Sickle Cell Disease Pain

August 23, 2023 updated by: Claudia R. Morris, Emory University

Phase 2 Randomized Control Trial of Arginine Therapy for Pediatric Sickle Cell Disease Pain

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The purpose of this study is to determine the effects of IV L-arginine hydrochloride therapy in children with sickle cell disease (SCD) and vaso-occlusive pain events (VOE). Specifically, the impact on total opioid use (mg/kg) over the duration of their emergency department (ED) visit and hospital stay will be evaluated.

Study Type

Interventional

Enrollment (Actual)

108

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30342
        • Children's Healthcare of Atlanta at Scottish Rite
      • Atlanta, Georgia, United States, 30322
        • Children's Healthcare of Atlanta at Egleston
      • Atlanta, Georgia, United States, 30303
        • Children's Healthcare of Atlanta at Hugh Spalding

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 years to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • Newly started on HU for <3 months
  • Not an appropriate candidate in the investigator's judgment
  • Patient refusal

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: L-Arginine
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
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.
Other Names:
  • Arginine
Experimental: Loading Dose and L-Arginine
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
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.
Other Names:
  • Arginine
Drug: L-arginine Loading Dose
One loading dose of L-arginine will be dispensed intravenously (IV) at 200 mg/kg
Other Names:
  • Arginine
Placebo Comparator: Placebo
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
Placebo of intravenous (IV) normal saline 1-2 ml/kg three times a day until discharge from the emergency department (ED) or hospital.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total Parenteral Opioid Use in IV Morphine Equivalents
Time Frame: Post study drug delivery to discharge from the hospital (Up to 8 days)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Length of Hospital Stay
Time Frame: Discharge (Up to 8 days)
The total number of hours spent in the hospital from study drug delivery to time of discharge.
Discharge (Up to 8 days)
Time to Vaso-occlusive Pain Event (VOE) Resolution in Emergency Department
Time Frame: Post study drug delivery (Up to 8 hours)
The total number of hours between study drug delivery and the last parenteral opioid.
Post study drug delivery (Up to 8 hours)
Time to Vaso-occlusive Pain Event (VOE) Resolution in Hospital
Time Frame: Post study drug delivery until discharge (up to 8 days)
The total number of hours between study drug delivery and time of last parenteral opioid use, pain relief improved to tolerate oral pain medications
Post study drug delivery until discharge (up to 8 days)
Change in Vaso-occlusive Pain (VOE) Scores
Time Frame: Baseline, Time of discharge (Up to 8 days)
Pain associated with VOE will be measured on a scale of 0-10, by asking subjects to rate their pain level on a subjective scale from 0 to 10, with the ends representing the extreme limits of "no-pain" (0) and "worst pain" (10).
Baseline, Time of discharge (Up to 8 days)
Length of Emergency Department (ED) Stay
Time Frame: Until discharge or Hospital Admission (Up to 24 hours)
Total hours from time of ED triage to ED discharge or hospital admission.
Until discharge or Hospital Admission (Up to 24 hours)
Rate of Emergency Department (ED) Discharge
Time Frame: Post emergency department admission (Up to 24 hours)
Number of participants discharged from ED without a hospital ward admission.
Post emergency department admission (Up to 24 hours)
Total Opioid Dose (ORAL + Parenteral) in mg/kg IV Morphine Equivalents
Time Frame: Post study drug delivery up to hospital discharge (Up to 8 days)
Total opioid dose (ORAL + Parenteral) in mg/kg IV morphine equivalents after study drug delivery up to hospital discharge (up to 8 days)
Post study drug delivery up to hospital discharge (Up to 8 days)
Total Number of Study Drug Doses
Time Frame: Duration of study (Up to 8 days)
The total number of study drug doses given throughout the study period.
Duration of study (Up to 8 days)
Rate of Acute Chest Syndrome
Time Frame: Duration of study (Up to 8 days)
Number of participants who develop acute chest syndrome (not diagnosed prior to study drug delivery) throughout the study period.
Duration of study (Up to 8 days)
Rate of Blood Transfusion
Time Frame: Duration of study (Up to 8 days)
Number of participants requiring a blood transfusion throughout the study period.
Duration of study (Up to 8 days)
Oxygen Saturation Level
Time Frame: At time of Emergency Department Admission
Average oxygen saturation level of participants at time of ED arrival
At time of Emergency Department Admission
Oxygen Saturation Level
Time Frame: At time of hospital admission and at time of Hospital discharge (Up to 8 days)
The difference in oxygen saturation levels from emergency department arrival to hospital discharge.
At time of hospital admission and at time of Hospital discharge (Up to 8 days)
Rate of Return Visits to Emergency Department (ED) Within 72 Hours
Time Frame: Post hospital discharge (within 72 hours)
Number of ED visits from patients who have been discharged within the previous 72 hours.
Post hospital discharge (within 72 hours)
Rate of Hospital Re-admissions Within 72 Hours
Time Frame: Post hospital discharge (within 72 hours)
Number of patients readmitted to the hospital within 72 hours of discharge.
Post hospital discharge (within 72 hours)
Rate of Return Visits to Emergency Department (ED) Within 30 Days
Time Frame: Post hospital discharge (within 30 days)
Number of ED visits from patients who have been discharged within the previous 30 days.
Post hospital discharge (within 30 days)
Rate of Hospital Re-admissions With 30 Days
Time Frame: Post hospital discharge (within 30 days)
Number of patients readmitted to the hospital within 30 days of discharge.
Post hospital discharge (within 30 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Emory University

Collaborators

National Center for Complementary and Integrative Health (NCCIH)
Children's Healthcare of Atlanta

Investigators

  • Principal Investigator: Claudia Morris, MD, Emory University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2016

Primary Completion (Actual)

February 21, 2021

Study Completion (Actual)

February 21, 2021

Study Registration Dates

First Submitted

August 27, 2015

First Submitted That Met QC Criteria

August 27, 2015

First Posted (Estimated)

August 31, 2015

Study Record Updates

Last Update Posted (Actual)

September 6, 2023

Last Update Submitted That Met QC Criteria

August 23, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00076988
  • 1K24AT009893-01 (U.S. NIH Grant/Contract)
  • FD-R-004814 (Other Grant/Funding Number: FDA)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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