Don't get left behind! The modernized ClinicalTrials.gov is coming. Check it out now.
Say goodbye to ClinicalTrials.gov!
The new site is coming soon - go to the modernized ClinicalTrials.gov
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Arginine Therapy for Sickle Cell Disease Pain

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02536170
Recruitment Status : Completed
First Posted : August 31, 2015
Results First Posted : June 6, 2022
Last Update Posted : June 6, 2022
Sponsor:
Collaborators:
Children's Healthcare of Atlanta
National Center for Complementary and Integrative Health (NCCIH)
Information provided by (Responsible Party):
Claudia R. Morris, Emory University

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Vaso-occlusive Pain Episode Drug: L-arginine Drug: L-arginine Loading Dose Other: Placebo Phase 2

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 Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 108 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Phase 2 Randomized Control Trial of Arginine Therapy for Pediatric Sickle Cell Disease Pain
Study Start Date : February 2016
Actual Primary Completion Date : February 21, 2021
Actual Study Completion Date : February 21, 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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 Name: 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 Name: Arginine

Drug: L-arginine Loading Dose
One loading dose of L-arginine will be dispensed intravenously (IV) at 200 mg/kg
Other Name: 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.


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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

  4. 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).

  5. 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.

  6. 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.

  7. 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)

  8. 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.

  9. 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.

  10. Rate of Blood Transfusion [ Time Frame: Duration of study (Up to 8 days) ]
    Number of participants requiring a blood transfusion throughout the study period.

  11. Oxygen Saturation Level [ Time Frame: At time of Emergency Department Admission ]
    Average oxygen saturation level of participants at time of ED arrival

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   3 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02536170


Locations
Layout table for location information
United States, Georgia
Children's Healthcare of Atlanta at Hugh Spalding
Atlanta, Georgia, United States, 30303
Children's Healthcare of Atlanta at Egleston
Atlanta, Georgia, United States, 30322
Children's Healthcare of Atlanta at Scottish Rite
Atlanta, Georgia, United States, 30342
Sponsors and Collaborators
Emory University
Children's Healthcare of Atlanta
National Center for Complementary and Integrative Health (NCCIH)
Investigators
Layout table for investigator information
Principal Investigator: Claudia Morris, MD Emory University
  Study Documents (Full-Text)

Documents provided by Claudia R. Morris, Emory University:
Study Protocol and Statistical Analysis Plan  [PDF] December 23, 2020
Informed Consent Form  [PDF] October 14, 2020

More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Claudia R. Morris, Professor, Emory University
ClinicalTrials.gov Identifier: NCT02536170    
Other Study ID Numbers: IRB00076988
FD-R-004814 ( Other Grant/Funding Number: FDA )
1K24AT009893-01 ( U.S. NIH Grant/Contract )
First Posted: August 31, 2015    Key Record Dates
Results First Posted: June 6, 2022
Last Update Posted: June 6, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Claudia R. Morris, Emory University:
Arginine Therapy
Additional relevant MeSH terms:
Layout table for MeSH terms
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
 Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn