Clinical trial NCT02536170: Arginine Therapy for Sickle Cell Disease Pain
Official title: Phase 2 Randomized Control Trial of Arginine Therapy for Pediatric Sickle Cell Disease Pain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sickle Cell Disease
Vaso-occlusive Pain Episode
Keywords: Arginine Therapy
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: Children's Healthcare of Atlanta
name: National Center for Complementary and Integrative Health (NCCIH)
First posted: 2015-08-31
Enrollment: 108
Sex: ALL
Minimum age (years): 3
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Total Parenteral Opioid Use in IV Morphine Equivalents
timeFrame: Post study drug delivery to discharge from the hospital (Up to 8 days)
Secondary outcomes:
measure: Length of Hospital Stay
timeFrame: Discharge (Up to 8 days)
measure: Time to Vaso-occlusive Pain Event (VOE) Resolution in Emergency Department
timeFrame: Post study drug delivery (Up to 8 hours)
measure: Time to Vaso-occlusive Pain Event (VOE) Resolution in Hospital
timeFrame: Post study drug delivery until discharge (up to 8 days)
measure: Change in Vaso-occlusive Pain (VOE) Scores
timeFrame: Baseline, Time of discharge (Up to 8 days)
measure: Length of Emergency Department (ED) Stay
timeFrame: Until discharge or Hospital Admission (Up to 24 hours)
measure: Rate of Emergency Department (ED) Discharge
timeFrame: Post emergency department admission (Up to 24 hours)
measure: Total Opioid Dose (ORAL + Parenteral) in mg/kg IV Morphine Equivalents
timeFrame: Post study drug delivery up to hospital discharge (Up to 8 days)
measure: Total Number of Study Drug Doses
timeFrame: Duration of study (Up to 8 days)
measure: Rate of Acute Chest Syndrome
timeFrame: Duration of study (Up to 8 days)
measure: Rate of Blood Transfusion
timeFrame: Duration of study (Up to 8 days)
measure: Oxygen Saturation Level
timeFrame: At time of Emergency Department Admission
measure: Oxygen Saturation Level
timeFrame: At time of hospital admission and at time of Hospital discharge (Up to 8 days)
measure: Rate of Return Visits to Emergency Department (ED) Within 72 Hours
timeFrame: Post hospital discharge (within 72 hours)
measure: Rate of Hospital Re-admissions Within 72 Hours
timeFrame: Post hospital discharge (within 72 hours)
measure: Rate of Return Visits to Emergency Department (ED) Within 30 Days
timeFrame: Post hospital discharge (within 30 days)
measure: Rate of Hospital Re-admissions With 30 Days
timeFrame: Post hospital discharge (within 30 days)
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta at Hugh Spalding
state: Georgia
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta at Egleston
state: Georgia
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta at Scottish Rite
state: Georgia
Study officials:
affiliation: Emory University
name: Claudia Morris, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bakshi N, Liu Z, Gillespie S, Keesari R, Leake D, Khemani K, Kumari P, Rees CA, Dampier C, Morris CR. Patient-reported outcomes in children with sickle cell disease at presentation for an acute pain episode. Blood Adv. 2023 Sep 12;7(17):5103-5107. doi: 10.1182/bloodadvances.2021006794. No abstract available.
citation: Reyes LZ, Figueroa J, Leake D, Khemani K, Kumari P, Bakshi N, Lane PA, Dampier C, Morris CR. Safety of intravenous arginine therapy in children with sickle cell disease hospitalized for vaso-occlusive pain: A randomized placebo-controlled trial in progress. Am J Hematol. 2022 Jan 1;97(1):E21-E24. doi: 10.1002/ajh.26396. Epub 2021 Nov 12. No abstract available.
citation: Morris CR, Brown LAS, Reynolds M, Dampier CD, Lane PA, Watt A, Kumari P, Harris F, Manoranjithan S, Mendis RD, Figueroa J, Shiva S. Impact of arginine therapy on mitochondrial function in children with sickle cell disease during vaso-occlusive pain. Blood. 2020 Sep 17;136(12):1402-1406. doi: 10.1182/blood.2019003672.