Back to resultsSickle Cell Disease Treatment With Arginine Therapy (STArT) Trial (STArT)
Primary Purpose
Sickle Cell Disease
Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Arginine Hydrochloride
Normal saline
Sponsored by
About this trial
This is an interventional treatment trial for Sickle Cell Disease focused on measuring Arginine Therapy, Pain management
Eligibility Criteria
Inclusion Criteria:
- Age 3-21 years of age, inclusive; AND
- Established diagnosis of sickle cell disease (any genotype); AND
- 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:
- Responds to 2 doses of IV opioids sufficiently for outpatient management
- Greater than 12 hours from first dose of intravenous opioids to treat current pain in acute care setting
- Hemoglobin less than 5 gm/dL or emergent need for red blood cell transfusion for hemodynamically unstable patient; OR
- Ketamine use in the emergency department for treatment of VOE; OR
- Glutamine within 30 days; OR
- New SCD drug use < 3 months (e.g. Hydroxyurea, voxelotor, crizanlizumab, etc) OR
- Acute mental status or neurological changes; OR
- Acute stroke or clinical concern for stroke; OR
- Three or more ED visits for sickle cell related pain receiving parenteral opioids in previous 7 days (not including current ED visit); OR
- Hospital discharge within previous 7 days; OR
- Hypotension requiring clinical intervention; hemodynamic instability; septic shock; OR
- Previous randomization in this arginine phase 3 RCT; OR
- Use of inhaled nitric oxide, sildenafil or arginine within the last month; OR
- Non-English or non-Spanish speaking; OR
- pregnancy; OR
- Allergy to arginine; OR
- PI/clinical team concerns for compliance/issues that may adversely impact study participation/outcome; OR
- Adults 18 years or older who lack medical decision-making capacity to consent
Sites / Locations
- Children's Hospital Los AngelesRecruiting
- UCSF Benioff Children's HospitalRecruiting
- Children's National Medical CenterRecruiting
- Children's Healthcare of Atlanta at Hughes SpaldingRecruiting
- Children's Healthcare of Atlanta at EglestonRecruiting
- Washington University/St. Louis Children's HospitalRecruiting
- Nationwide Children's HospitalRecruiting
- Children's Hospital of PhiladelphiaRecruiting
- Texas Children's Hospital/Baylor College of MedicineRecruiting
- Medical College of Wisconsin/Wisconsin Children's HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Arginine Hydrochloride
Placebo
Arm Description
Arginine is a nutritional supplement in parenteral form
Normal saline
Outcomes
Primary Outcome Measures
Change in time-to-crisis resolution
Time in hours from study drug delivery to time of last dose of parenteral opioid delivery
Secondary Outcome Measures
Change in total parenteral opioid use
Total parenteral opioid use (morphine equivalents, mg/kg)
Change in pain scores
Daily highest and lowest pain scores will be recorded. 0-10 scale, 10 is strongest pain
Change in PROMIS Pain Interference score
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).
Change in PROMIS Pain Behavior score
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)
Change in PROMIS Fatigue score
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).
Full Information
NCT ID
NCT04839354
First Posted
April 8, 2021
Last Updated
May 10, 2023
Sponsor
Claudia R. Morris
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
1. Study Identification
Unique Protocol Identification Number
NCT04839354
Brief Title
Sickle Cell Disease Treatment With Arginine Therapy (STArT) Trial
Acronym
STArT
Official Title
Sickle Cell Disease Treatment With Arginine Therapy (STArT) Trial
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 21, 2021 (Actual)
Primary Completion Date
April 2027 (Anticipated)
Study Completion Date
April 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Claudia R. Morris
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease
Keywords
Arginine Therapy, Pain management
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
360 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Arginine Hydrochloride
Arm Type
Experimental
Arm Description
Arginine is a nutritional supplement in parenteral form
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Normal saline
Intervention Type
Drug
Intervention Name(s)
Arginine Hydrochloride
Intervention Description
One-time L-arginine loading dose (200 mg/kg IV) + standard dose (100 mg/kg IV TID)
Intervention Type
Other
Intervention Name(s)
Normal saline
Intervention Description
Placebo (normal saline) loading dose (2ml/kg IV) + 1ml/kg IV TID
Primary Outcome Measure Information:
Title
Change in time-to-crisis resolution
Description
Time in hours from study drug delivery to time of last dose of parenteral opioid delivery
Time Frame
Date and time of first study drug administration and last IV opioid treatment - up to 2 months
Secondary Outcome Measure Information:
Title
Change in total parenteral opioid use
Description
Total parenteral opioid use (morphine equivalents, mg/kg)
Time Frame
Time of IV placement, opioid monitoring up to 2 months
Title
Change in pain scores
Description
Daily highest and lowest pain scores will be recorded. 0-10 scale, 10 is strongest pain
Time Frame
Time of IV placement, and on the day of discharge up to 2 months
Title
Change in PROMIS Pain Interference score
Description
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).
Time Frame
Within 12 hours of study drug delivery, and on the day of discharge up to 2 months
Title
Change in PROMIS Pain Behavior score
Description
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)
Time Frame
Within 12 hours of study drug delivery, and on the day of discharge up to 2 months
Title
Change in PROMIS Fatigue score
Description
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).
Time Frame
Within 12 hours of study drug delivery, and on the day of discharge up to 2 months
Other Pre-specified Outcome Measures:
Title
Change in Medication Quantification Score (MQS)
Description
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.
Time Frame
Pre-dose and on day of discharge up to 2 months
Title
Hospital length of stay in children
Description
Hospital length of stay in children (days) will be recorded.
Time Frame
Up to 6 months
Title
Change in Pediatric PROMIS score
Description
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).
Time Frame
Within 12 hours of study drug delivery, and on the day of discharge up to 2 months
Title
Change in Pediatric QL SCD score
Description
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)
Time Frame
Within 12 hours of study drug delivery, and on the day of discharge up to 2 months
Title
Change in Arginine bioavailability
Description
Pharmacokinetic study will measure peak plasma arginine concentration
Time Frame
Prior to study drug delivery (pre-Dose), on day 2 and prior to discharge up to 2 months
Title
Change in mitochondrial function
Description
Mitochondrial respiratory complex activities will be measured to estimate mitochondrial function
Time Frame
Prior to study drug delivery (pre-Dose), on day 2 and prior to discharge up to 2 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 3-21 years of age, inclusive; AND
Established diagnosis of sickle cell disease (any genotype); AND
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:
Responds to 2 doses of IV opioids sufficiently for outpatient management
Greater than 12 hours from first dose of intravenous opioids to treat current pain in acute care setting
Hemoglobin less than 5 gm/dL or emergent need for red blood cell transfusion for hemodynamically unstable patient; OR
Ketamine use in the emergency department for treatment of VOE; OR
Glutamine within 30 days; OR
New SCD drug use < 3 months (e.g. Hydroxyurea, voxelotor, crizanlizumab, etc) OR
Acute mental status or neurological changes; OR
Acute stroke or clinical concern for stroke; OR
Three or more ED visits for sickle cell related pain receiving parenteral opioids in previous 7 days (not including current ED visit); OR
Hospital discharge within previous 7 days; OR
Hypotension requiring clinical intervention; hemodynamic instability; septic shock; OR
Previous randomization in this arginine phase 3 RCT; OR
Use of inhaled nitric oxide, sildenafil or arginine within the last month; OR
Non-English or non-Spanish speaking; OR
pregnancy; OR
Allergy to arginine; OR
PI/clinical team concerns for compliance/issues that may adversely impact study participation/outcome; OR
Adults 18 years or older who lack medical decision-making capacity to consent
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Claudia Morris, MD
Phone
404-785-7141
Email
claudia.r.morris@emory.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Claudia Morris, MD
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Individual Site Status
Recruiting
Facility Name
UCSF Benioff Children's Hospital
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Individual Site Status
Recruiting
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Individual Site Status
Recruiting
Facility Name
Children's Healthcare of Atlanta at Hughes Spalding
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
03322
Country
United States
Individual Site Status
Recruiting
Facility Name
Children's Healthcare of Atlanta at Egleston
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Claudia Morris, MD
Phone
404-785-7141
Email
claudia.r.morris@emory.edu
Facility Name
Washington University/St. Louis Children's Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Individual Site Status
Recruiting
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Name
Texas Children's Hospital/Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Name
Medical College of Wisconsin/Wisconsin Children's Hospital
City
Wauwatosa
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Time Frame
Will be available starting 2029
IPD Sharing Access Criteria
No restrictions
Learn more about this trial
Sickle Cell Disease Treatment With Arginine Therapy (STArT) Trial
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