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Sickle Cell Disease Treatment With Arginine Therapy (STArT) Trial (STArT)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04839354
Recruitment Status : Recruiting
First Posted : April 9, 2021
Last Update Posted : January 13, 2022
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Claudia R. Morris MD, Emory University

Brief Summary:
The trial of IV arginine therapy in children with Vaso-occlusive painful episodes (VOE) in sickle cell disease (SCD) is designed to further knowledge on efficacy and safety of the therapy.

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Drug: Arginine Hydrochloride Other: Normal saline Phase 3

Detailed Description:
The trial is designed as a double-blind, placebo controlled, randomized, phase 3, multi-center trial of IV arginine therapy in children with Vaso-occlusive painful episodes (VOE) in sickle cell disease (SCD) to further knowledge on efficacy and safety of the therapy. The exploratory objective is to more fully characterize the arginine metabolome in children with SCD during VOE, and evaluate the effects of arginine therapy on global arginine bioavailability and mitochondrial function together with important clinical outcomes (time to VOE resolution, pain scores, total parenteral opioid use, Patient-Reported Outcomes (PROs), and hospital length of stay in children with SCD and VOE.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 360 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Sickle Cell Disease Treatment With Arginine Therapy (STArT) Trial
Actual Study Start Date : June 21, 2021
Estimated Primary Completion Date : April 2027
Estimated Study Completion Date : April 2027


Arm Intervention/treatment
Experimental: Arginine Hydrochloride
Arginine is a nutritional supplement in parenteral form
Drug: Arginine Hydrochloride
One-time L-arginine loading dose (200 mg/kg IV) + standard dose (100 mg/kg IV TID)

Placebo Comparator: Placebo
Normal saline
Other: Normal saline
Placebo (normal saline) loading dose (2ml/kg IV) + 1ml/kg IV TID




Primary Outcome Measures :
  1. Change in time-to-crisis resolution [ Time Frame: Date and time of first study drug administration and last IV opioid treatment - up to 2 months ]
    Time in hours from study drug delivery to time of last dose of parenteral opioid delivery


Secondary Outcome Measures :
  1. Change in total parenteral opioid use [ Time Frame: Time of IV placement, opioid monitoring up to 2 months ]
    Total parenteral opioid use (morphine equivalents, mg/kg)

  2. Change in pain scores [ Time Frame: Time of IV placement, and on the day of discharge up to 2 months ]
    Daily highest and lowest pain scores will be recorded. 0-10 scale, 10 is strongest pain

  3. Change in PROMIS Pain Interference score [ Time Frame: Within 12 hours of study drug delivery, and on the day of discharge up to 2 months ]
    PROMIS: pain Interference (8 items). PROMIS measures are scored on the T-score metric. High scores mean more of the concept being measured (e.g., more pain).

  4. Change in PROMIS Pain Behavior score [ Time Frame: Within 12 hours of study drug delivery, and on the day of discharge up to 2 months ]
    PROMIS: pain behavior (8 items). PROMIS measures are scored on the T-score metric. High scores mean more of the concept being measured (e.g., more pain)

  5. Change in PROMIS Fatigue score [ Time Frame: Within 12 hours of study drug delivery, and on the day of discharge up to 2 months ]
    PROMIS: fatigue (8 items). PROMIS measures are scored on the T-score metric. High scores mean more of the concept being measured (e.g., more fatigue).


Other Outcome Measures:
  1. Change in Medication Quantification Score (MQS) [ Time Frame: Pre-dose and on day of discharge up to 2 months ]
    Medication Quantification Score (MQS) is a tool to objectively quantify pain. It computes a single numeric value for a patient's pain medication profile. This number is used to track pain levels through a treatment course.

  2. Hospital length of stay in children [ Time Frame: Up to 6 months ]
    Hospital length of stay in children (days) will be recorded.

  3. Change in Pediatric PROMIS score [ Time Frame: Within 12 hours of study drug delivery, and on the day of discharge up to 2 months ]
    Pediatric PROMIS: (35 items) To be completed by patients ages 8-17 years of age and parents of children ages 5-17 years of age: (a)pain behavior (8 items), (b)pain interference (8 items), (c)pain intensity (1 item), (d)physical stress experiences (8 items), (e)fatigue (10 items). PROMIS measures are scored on the T-score metric. High scores mean more of the concept being measured (e.g., more fatigue).

  4. Change in Pediatric QL SCD score [ Time Frame: Within 12 hours of study drug delivery, and on the day of discharge up to 2 months ]
    Peds QL SCD module (19 items) to be completed by children ages 5-17 years of age and parents of children ages 3-17 years of age: (a)Pain and Hurt (9 items), (b)Pain Impact (10 items)

  5. Change in Arginine bioavailability [ Time Frame: Prior to study drug delivery (pre-Dose), on day 2 and prior to discharge up to 2 months ]
    Pharmacokinetic study will measure peak plasma arginine concentration

  6. Change in mitochondrial function [ Time Frame: Prior to study drug delivery (pre-Dose), on day 2 and prior to discharge up to 2 months ]
    Mitochondrial respiratory complex activities will be measured to estimate mitochondrial function



Information from the National Library of Medicine

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

Inclusion Criteria:

  1. Age 3-21 years of age, inclusive; AND
  2. Established diagnosis of sickle cell disease (any genotype); AND
  3. Pain requiring medical care in an acute care setting (ED, hospital ward, day hospital, clinic) not attributable to non-sickle cell causes, treated with parenteral opioids.

Exclusion Criteria:

  1. Responds to 2 doses of IV opioids sufficiently for outpatient management
  2. Greater than 12 hours from first dose of intravenous opioids to treat current pain in acute care setting
  3. Hemoglobin less than 5 gm/dL or emergent need for red blood cell transfusion for hemodynamically unstable patient; OR
  4. Ketamine use in the emergency department for treatment of VOE; OR
  5. Glutamine within 30 days; OR
  6. New SCD drug use < 3 months (e.g. Hydroxyurea, voxelotor, crizanlizumab, etc) OR
  7. Acute mental status or neurological changes; OR
  8. Acute stroke or clinical concern for stroke; OR
  9. Three or more ED visits for sickle cell related pain receiving parenteral opioids in previous 7 days (not including current ED visit); OR
  10. Hospital discharge within previous 7 days; OR
  11. Hypotension requiring clinical intervention; hemodynamic instability; septic shock; OR
  12. Previous randomization in this arginine phase 3 RCT; OR
  13. Use of inhaled nitric oxide, sildenafil or arginine within the last month; OR
  14. Non-English or non-Spanish speaking; OR
  15. pregnancy; OR
  16. Allergy to arginine; OR
  17. PI/clinical team concerns for compliance/issues that may adversely impact study participation/outcome; OR
  18. Adults 18 years or older who lack medical decision-making capacity to consent

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): NCT04839354


Contacts
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Contact: Claudia Morris, MD 404-785-7141 claudia.r.morris@emory.edu

Locations
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United States, California
Children's Hospital Los Angeles Recruiting
Los Angeles, California, United States, 90027
UCSF Benioff Children's Hospital Recruiting
San Francisco, California, United States, 94158
United States, District of Columbia
Children's National Medical Center Recruiting
Washington, District of Columbia, United States, 20010
United States, Georgia
Children's Healthcare of Atlanta at Hughes Spalding Recruiting
Atlanta, Georgia, United States, 03322
Children's Healthcare of Atlanta at Egleston Recruiting
Atlanta, Georgia, United States, 30322
Contact: Claudia Morris, MD    404-785-7141    claudia.r.morris@emory.edu   
United States, Missouri
Washington University/St. Louis Children's Hospital Recruiting
Saint Louis, Missouri, United States, 63110
United States, Ohio
Nationwide Children's Hospital Recruiting
Columbus, Ohio, United States, 43205
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Texas Children's Hospital/Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
United States, Wisconsin
Medical College of Wisconsin/Wisconsin Children's Hospital Recruiting
Wauwatosa, Wisconsin, United States, 53226
Sponsors and Collaborators
Emory University
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Claudia Morris, MD Emory University
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Responsible Party: Claudia R. Morris MD, Principal Investigator, Emory University
ClinicalTrials.gov Identifier: NCT04839354    
Other Study ID Numbers: STUDY00002344
PECARN Protocol Number 050 ( Other Identifier: Pediatric Emergency Care Applied Research Network )
UG3HL148560 ( U.S. NIH Grant/Contract )
First Posted: April 9, 2021    Key Record Dates
Last Update Posted: January 13, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Will be available starting 2029
Access Criteria: No restrictions

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Claudia R. Morris MD, Emory University:
Arginine Therapy
Pain management
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn