Anemia, Sickle CellPhase 2ArginineNCT00513617
Effectiveness of Arginine as a Treatment for Sickle Cell Anemia
A Phase 2 study testing Arginine in people with Anemia, Sickle Cell, run by UCSF Benioff Children's Hospital Oakland at 17 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 5 years and older
- Conditions the study is for
- Anemia, Sickle Cell
- What is being tested?
- Arginine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 128 participants
- Where
- 17 sitesUnited States
- Study dates
- Jun 2004to Jan 2008
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
United States17 sites
Boston Medical Center
Boston, Massachusetts, 02118
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
Children's Medical Center of Dallas
Dallas, Texas, 75390
University of Colorado at Denver and Health Sciences Center--Sickle Cell Treatment and Research Center
Denver, Colorado, 80262
Duke University Medical Center
Durham, North Carolina, 27710
University of Mississippi Medical Center (Adult)
Jackson, Mississippi, 39215
University of Mississippi Medical Center (Pediatric)
Jackson, Mississippi, 39215
Kosair Children's Hospital
Louisville, Kentucky, 40202
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
Children's Hospital of Oakland and Research Institute
Oakland, California, 94609
Children's Hospital of Oklahoma
Oklahoma City, Oklahoma, 73104
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
St. Christopher's Children's Research Hospital
Philadelphia, Pennsylvania, 19134
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19444
University of California - San Francisco
San Francisco, California, 94143
Montefiore Medical Center
The Bronx, New York, 10463
Children's Hospital of Montefiore
The Bronx, New York, 10467
About this study
Official title: Arginine Supplementation in Sickle Cell Anemia: Physiological and Prophylactic Effects
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.
Read the 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.
- Conditions
- Anemia, Sickle Cell
- Being tested
- Arginine, Placebo
- Keywords
- Sickle Cell Disease, Anemia, Nitric Oxide, Vaso Occlusive Events, Arginine Supplementation
- Medical subject headings
- Anemia, Sickle Cell, Anemia, Vaso-Occlusive Crises
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ArginineDrug
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Low Dose | Active comparator | 0.05 g/kg/day Arginine Receives: Drug: Arginine |
| High Dose | Active comparator | 0.10 g/kg/day Arginine Receives: Drug: Arginine |
| Placebo | Placebo comparator | No Arginine Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Gardos Channel Activity
Gardos channel activity: a calcium (Ca2+)-activated K+ channel
Measured: 12 weeks after randomization
Nitric Oxide
Nitric oxide from plasma amino acids
Measured: 12 weeks after randomization
Mean Corpuscular Hemoglobin Concentration
Mean corpuscular hemoglobin concentration as measured by an Advia machine
Measured: 12 weeks after randomization
Secondary outcomes (4)
Soluble Vascular Cell Adhesion Molecule
Soluble vascular cell adhesion molecule (sVCAM) a vascular adhesion molecule
Measured: 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
Measured: 12 weeks after randomization
Endothelin-1
Endothelin-1 is a potent vasoconstrictor and pro-inflammatory agent which is elevated in SCD patients
Measured: 12 weeks after randomization
Fetal Hemoglobin
Fetal hemoglobin (HbF) as measured by the Advia machine
Measured: 12 weeks after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2007 (estimated)
- Study startJun 2004
- Primary completionSep 2007
- Study completionJan 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Anemia, Sickle CellStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 128 participants (actual)
Sponsor and investigators
- Lead sponsor
- UCSF Benioff Children's Hospital Oakland
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Investigators
- Lillian McMahon, MD, Principal investigator, Boston Medical CenterRathi Iyer, MD, Principal investigator, University of Mississippi Medical Center (Pediatric)Carolyn Bigelow, MD, Principal investigator, University of Mississippi Medical Center (Adult)Lennette Benjamin, MD, Principal investigator, Montefiore Medical CenterMary Fabry, MD, Principal investigator, Albert Einstein College of MedicineThomas Moulton, MD, Principal investigator, Children's Hospital of MontefioreKim Smith-Whitley, MD, Principal investigator, Children's Hospital of PhiladelphiaLaura DeCastro, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00513617
- Sponsor's protocol ID
- 485
- Other IDs
- U54HL070587-04
- Acronym
- Arginine
- Status last verified
- Jun 2009
- First submitted
- 6 Aug 2007
- Last updated
- 29 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Bolarinwa AB, Oduwole O, Okebe J, Ogbenna AA, Otokiti OE, Olatinwo AT. Antioxidant supplementation for sickle cell disease. Cochrane Database Syst Rev. 2024 May 22;5(5):CD013590. doi: 10.1002/14651858.CD013590.pub2.
PubMed 38775255
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Arginine Supplementation in Sickle Cell Anemia: Physiological and Prophylactic Effects
- ClinicalTrials.gov ID
- NCT00513617
- Acronym / sponsor ID
- Arginine / 485
- Conditions
- Anemia, Sickle Cell
- Keywords
- Sickle Cell Disease, Anemia, Nitric Oxide, Vaso Occlusive Events, Arginine Supplementation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 128 participants (actual)
- Lead sponsor
- UCSF Benioff Children's Hospital OaklandUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Jun 2004
- Primary completion
- Sep 2007 (actual)
- Study completion
- Jan 2008 (actual)
- First posted
- 8 Aug 2007 (estimated)
- Results
- Posted 4 Aug 2009
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Low Dose | Active comparator | Drug: Arginine0.05 g/kg/day Arginine |
| High Dose | Active comparator | Drug: Arginine0.10 g/kg/day Arginine |
| Placebo | Placebo comparator | Drug: PlaceboNo Arginine |
Who may qualify
- Ages
- 5 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ArginineDepending 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. | Drug | High Dose, Low Dose |
| PlaceboDepending 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. | Drug | Placebo |
Primary outcome
Gardos Channel Activity
Time frame: 12 weeks after randomization
Gardos channel activity: a calcium (Ca2+)-activated K+ channel
Nitric Oxide
Time frame: 12 weeks after randomization
Nitric oxide from plasma amino acids
Mean Corpuscular Hemoglobin Concentration
Time frame: 12 weeks after randomization
Mean corpuscular hemoglobin concentration as measured by an Advia machine
4 secondary outcomes
Soluble Vascular Cell Adhesion Molecule
Time frame: 12 weeks after randomization
8-iso-PGF2a
Time frame: 12 weeks after randomization
Endothelin-1
Time frame: 12 weeks after randomization
Fetal Hemoglobin
Time frame: 12 weeks after randomization
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38775255Bolarinwa AB, Oduwole O, Okebe J, Ogbenna AA, Otokiti OE, Olatinwo AT. Antioxidant supplementation for sickle cell disease. Cochrane Database Syst Rev. 2024 May 22;5(5):CD013590. doi: 10.1002/14651858.CD013590.pub2.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lillian McMahon, MD principal investigator
Boston Medical Center
Rathi Iyer, MD principal investigator
University of Mississippi Medical Center (Pediatric)
Carolyn Bigelow, MD principal investigator
University of Mississippi Medical Center (Adult)
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Arginine in people with Anemia, Sickle Cell, run by UCSF Benioff Children's Hospital Oakland at 17 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Aug 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Gardos Channel Activity (time frame: 12 weeks after randomization). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00513617, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2017.