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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
108

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Emory University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Center for Complementary and Integrative Health (NCCIH)
Children's Healthcare of Atlanta

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 21, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 21, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 27, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 27, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 31, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 6, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 23, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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