A Phase 2 interventional study of Arginine and Placebo in Anemia, Sickle Cell, sponsored by UCSF Benioff Children's Hospital Oakland. Completed at 17 sites in United States. Open to participants aged 5 Years and older. Per ClinicalTrials.gov, last updated 2017-03-29.
Sponsored by UCSF Benioff Children's Hospital Oakland · Phase 2, Interventional, and Treatment
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.
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.
1,733 studies on the registry are indexed under Anemia; 246 are open to participants now.
This study's enrollment of 128 is above the median of 94 across 1,291 interventional studies indexed under Anemia.
Browse Anemia studies →UCSF Benioff Children's Hospital Oakland is the lead sponsor of 53 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
0.05 g/kg/day Arginine
Drug: Arginine
0.10 g/kg/day Arginine
Drug: Arginine
No Arginine
Drug: Placebo
Depending on the weight of the child or adult, the patients took any where between 4-10 capsules 2 times a day. Patients weighing less than 45 kilograms were on the low dose active (or placebo) so the capsules were smaller. Patients greater than or equal to 45 kgs were on the high dose active or placebo, so these capsules were larger.
Depending on the weight of the child or adult, the patients took any where between 4-10 capsules 2 times a day. Patients weighing less than 45 kilograms were on the low dose active (or placebo) so the capsules were smaller. Patients greater than or equal to 45 kgs were on the high dose active or placebo, so these capsules were larger.
Gardos Channel Activity
Gardos channel activity: a calcium (Ca2+)-activated K+ channel
Time frame: 12 weeks after randomization
Nitric Oxide
Nitric oxide from plasma amino acids
Time frame: 12 weeks after randomization
Mean Corpuscular Hemoglobin Concentration
Mean corpuscular hemoglobin concentration as measured by an Advia machine
Time frame: 12 weeks after randomization
Soluble Vascular Cell Adhesion Molecule
Soluble vascular cell adhesion molecule (sVCAM) a vascular adhesion molecule
Time frame: 12 weeks after randomization
8-iso-PGF2a
8-iso-PGF2a is a measure of lipid peroxidation and oxidative damage in vivo measured by enzyme immunoassay kit from Cayman chemical
Time frame: 12 weeks after randomization
Endothelin-1
Endothelin-1 is a potent vasoconstrictor and pro-inflammatory agent which is elevated in SCD patients
Time frame: 12 weeks after randomization
Fetal Hemoglobin
Fetal hemoglobin (HbF) as measured by the Advia machine
Time frame: 12 weeks after randomization
Enrolled subjects at participating sites from May 2004 through July 2007. Sites consisted of sickle cell treatment centers from across the United States.
| Milestone | Low Dose | High Dose | Placebo |
|---|---|---|---|
| Started | 36 | 35 | 38 |
| Completed | 25 | 25 | 30 |
| Not completed | 11 | 10 | 8 |
Gardos channel activity: a calcium (Ca2+)-activated K+ channel
| mmol/10^13 cells x min | Low Dose | High Dose | Placebo |
|---|---|---|---|
| Gardos Channel Activity | -0.0342 ± 0.2341 | 0.0043 ± 0.3028 | 0.1076 ± 0.2822 |
Soluble vascular cell adhesion molecule (sVCAM) a vascular adhesion molecule
Results for this outcome have not been posted.
Nitric oxide from plasma amino acids
| uM | Low Dose | High Dose | Placebo |
|---|---|---|---|
| Nitric Oxide | -3.8697 ± 15.7574 | 2.9250 ± 11.1646 | -3.0265 ± 18.6887 |
Mean corpuscular hemoglobin concentration as measured by an Advia machine
| g/dL | Low Dose | High Dose | Placebo |
|---|---|---|---|
| Mean Corpuscular Hemoglobin Concentration | -1.8485 ± 6.3092 | 0.7692 ± 2.2165 | -0.0705 ± 1.4422 |
8-iso-PGF2a is a measure of lipid peroxidation and oxidative damage in vivo measured by enzyme immunoassay kit from Cayman chemical
Results for this outcome have not been posted.
Endothelin-1 is a potent vasoconstrictor and pro-inflammatory agent which is elevated in SCD patients
Results for this outcome have not been posted.
Fetal hemoglobin (HbF) as measured by the Advia machine
Results for this outcome have not been posted.
| Age, Categorical(Participants) | Low Dose | High Dose | Placebo | Total |
|---|---|---|---|---|
| <=18 years | 14 | 18 | 18 | 50 |
| Between 18 and 65 years | 22 | 17 | 20 | 59 |
| >=65 years | 0 | 0 | 0 | 0 |
| Age, Continuous(years) | Low Dose | High Dose | Placebo | Total |
|---|---|---|---|---|
| Mean | 24.5 ± 12.85 | 20.0 ± 10.01 | 21.0 ± 11.49 | 23.2 ± 11.75 |
| Sex: Female, Male(Participants) | Low Dose | High Dose | Placebo | Total |
|---|---|---|---|---|
| Female | 21 | 19 | 20 | 60 |
| Male | 15 | 16 | 18 | 49 |
| Region of Enrollment(participants) | Low Dose | High Dose | Placebo | Total |
|---|---|---|---|---|
| United States | 36 | 35 | 38 | 109.0 |
| Genotype of SCD(participants) | Low Dose | High Dose | Placebo | Total |
|---|---|---|---|---|
| Sickle cell S-Beta Thalassemia (SB0) | 2 | 3 | 2 | 7.0 |
| Sickle cell Anemia (SS) | 34 | 32 | 36 | 102.0 |
This study is completed, as verified in Jun 2009. You cannot join it, but the record below documents what was studied.
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UCSF Benioff Children's Hospital Oakland