Sickle Cell Disease Treatment With Arginine Therapy (STArT) Trial

• Sponsor: Emory University (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04839354
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 360
• Locations: 10
• Arms: 2
• Anticipated Duration (Months): 69.3
• Patients Per Site: 36
• Patients Per Site Per Month: 0.5

Study Details

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.

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.

Study Design

• Study Type: Interventional
• Anticipated 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: Jun 21, 2021
• Anticipated Primary Completion Date: Apr 1, 2027
• Anticipated Study Completion Date: Apr 1, 2027

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change in time-to-crisis resolution [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 of IV placement, opioid monitoring up to 2 months]

   Total parenteral opioid use (morphine equivalents, mg/kg)

2. Change in pain scores [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 [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 [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 [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) [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 [Up to 6 months]

   Hospital length of stay in children (days) will be recorded.

3. Change in Pediatric PROMIS score [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 [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 [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 [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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Years to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
2	UCSF Benioff Children's Hospital	San Francisco	California	United States	94158
3	Children's National Medical Center	Washington	District of Columbia	United States	20010
4	Children's Healthcare of Atlanta at Hughes Spalding	Atlanta	Georgia	United States	03322
5	Children's Healthcare of Atlanta at Egleston	Atlanta	Georgia	United States	30322
6	Washington University/St. Louis Children's Hospital	Saint Louis	Missouri	United States	63110
7	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
8	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
9	Texas Children's Hospital/Baylor College of Medicine	Houston	Texas	United States	77030
10	Medical College of Wisconsin/Wisconsin Children's Hospital	Wauwatosa	Wisconsin	United States	53226

Sponsors and Collaborators

• Emory University
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Claudia Morris, MD, Emory University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Claudia R. Morris MD, Principal Investigator, Emory University
• ClinicalTrials.gov Identifier: NCT04839354
• Other Study ID Numbers: STUDY00002344; PECARN Protocol Number 050; UG3HL148560
• First Posted: Apr 9, 2021
• Last Update Posted: Jan 13, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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, Principal Investigator, Emory University: Arginine Therapy; Pain management
• Additional relevant MeSH terms: Anemia, Sickle Cell

Study Results

No Results Posted as of Jan 13, 2022