Clinical trial NCT00513617: Effectiveness of Arginine as a Treatment for Sickle Cell Anemia
Official title: Arginine Supplementation in Sickle Cell Anemia: Physiological and Prophylactic Effects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anemia, Sickle Cell
Keywords: Sickle Cell Disease
Anemia
Nitric Oxide
Vaso Occlusive Events
Arginine Supplementation
Lead sponsor: UCSF Benioff Children's Hospital Oakland
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2007-08-08
Enrollment: 128
Sex: ALL
Minimum age (years): 5
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Sickle cell disease (SCD), also known as sickle cell anemia, is an inherited genetic disease that can cause intense pain episodes. This study will evaluate the effectiveness of the nutritional supplement arginine at improving blood cell function and disease symptoms in people with SCD.

Detailed description: SCD is an inherited blood disorder. Symptoms include anemia, infections, organ damage, and intense episodes of pain that are called "sickle cell crises." SCD is caused by an abnormal type of hemoglobin, which is a protein inside red blood cells that carries oxygen. In people with SCD, the abnormal hemoglobin distorts the shape of the red blood cells. This causes the red blood cells to clump together, decreasing blood flow and oxygen delivery to the body's tissues. The reduced levels of oxygen can lead to sickle cell crises and tissue damage. Hemolysis, the destruction of red blood cells, is also a hallmark of SCD. During hemolysis, hemoglobin is released into the bloodstream, where it removes nitric oxide (NO), a natural chemical in the body that expands blood vessels. Arginase, another protein released during hemolysis, removes arginine from the bloodstream, which can also lead to decreased NO levels. The lack of NO constricts blood vessels, further contributing to painful sickle cell crises. Arginine supplementation may increase healthy hemoglobin and NO production and, in turn, prevent or reduce sickle cell crises. The purpose of this study is to evaluate the effectiveness of arginine at increasing NO levels, improving red blood cell function, and reducing hospitalizations and pain medication use in people with SCD.

This study will enroll children and adults with SCD. Participants will be randomly assigned to receive twice daily doses of either a low dose of arginine, a high dose of arginine, or placebo for 12 weeks. Study visits will occur at baseline, three times during Month 1, and Weeks 8, 12, 14, and 16. Each study visit will include an echocardiogram to measure heart activity, blood collection, and a medical history review to identify adverse events, pain medication usage, headaches, emergency department visits, and hospitalizations.

Eligibility criteria: Inclusion Criteria:

* Established diagnosis of H SS or S-beta thalassemia
* History of at least one vaso-occlusive pain event in the 12 months prior to study entry
* Regular compliance with comprehensive medical care
* In a steady disease state and not in the midst of any acute complication due to SCD at study entry

Exclusion Criteria:

* Inability to take or tolerate oral medications
* Liver dysfunction (i.e., SGPT level greater than or equal to two times the normal limit and albumin level less than or equal to 3.2 g/dL)
* Kidney dysfunction ( i.e., creatinine level greater than or equal to 1.2 mg/dL for children and greater than or equal to 1.4 mg/dL for adults)
* Allergy to arginine
* Pregnant
* Received a blood transfusion within the 90 days prior to study entry
* More than 10 hospital admissions for pain in the 12 months prior to study entry
* Daily use of opioids and experiencing unstable pain that interferes with work or daily routine
* Required more than 3 hospital admissions and more than 10 emergency department/day hospital visits in the 12 months prior to study entry
* Received treatment with hydroxyurea within the 90 days prior to study entry
* Received treatment with any investigational drug in the 90 days prior to study entry

Primary outcomes:
measure: Gardos Channel Activity
timeFrame: 12 weeks after randomization
measure: Nitric Oxide
timeFrame: 12 weeks after randomization
measure: Mean Corpuscular Hemoglobin Concentration
timeFrame: 12 weeks after randomization
Secondary outcomes:
measure: Soluble Vascular Cell Adhesion Molecule
timeFrame: 12 weeks after randomization
measure: 8-iso-PGF2a
timeFrame: 12 weeks after randomization
measure: Endothelin-1
timeFrame: 12 weeks after randomization
measure: Fetal Hemoglobin
timeFrame: 12 weeks after randomization
Other outcomes:
Locations:
city: Oakland
country: United States
facility: Children's Hospital of Oakland and Research Institute
state: California
city: San Francisco
country: United States
facility: University of California - San Francisco
state: California
city: Denver
country: United States
facility: University of Colorado at Denver and Health Sciences Center--Sickle Cell Treatment and Research Center
state: Colorado
city: Louisville
country: United States
facility: Kosair Children's Hospital
state: Kentucky
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Jackson
country: United States
facility: University of Mississippi Medical Center (Adult)
state: Mississippi
city: Jackson
country: United States
facility: University of Mississippi Medical Center (Pediatric)
state: Mississippi
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Bronx
country: United States
facility: Children's Hospital of Montefiore
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Oklahoma City
country: United States
facility: Children's Hospital of Oklahoma
state: Oklahoma
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Philadelphia
country: United States
facility: St. Christopher's Children's Research Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Dallas
country: United States
facility: Children's Medical Center of Dallas
state: Texas
Study officials:
affiliation: Boston Medical Center
name: Lillian McMahon, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Mississippi Medical Center (Pediatric)
name: Rathi Iyer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Mississippi Medical Center (Adult)
name: Carolyn Bigelow, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Montefiore Medical Center
name: Lennette Benjamin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Albert Einstein College of Medicine
name: Mary Fabry, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital of Montefiore
name: Thomas Moulton, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital of Philadelphia
name: Kim Smith-Whitley, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Laura DeCastro, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of North Carolina, Chapel Hill
name: Kenneth Ataga, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Thomas Jefferson University
name: Samir K. Ballas, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Norton Healthcare
name: Sal Bertalone, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Christopher's Childrens Hospital
name: Carlton Dampier, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: William Mentzer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Jude's Childrens Research Hospital
name: Winfred Wang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Jude Children's Research Hospital
name: Ulrike Reiss, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Medical Center Dallas
name: Cynthia Rutherford, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Colorado, Denver
name: Kathryn Hassell, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital of Oklahoma
name: Joan Parkhurst Cain, MD
role: PRINCIPAL_INVESTIGATOR
References: