Arginine Supplementation in Sickle Cell Anemia: Physiological and Prophylactic Effects
Effectiveness of Arginine as a Treatment for Sickle Cell Anemia
Sponsors
Lead Sponsor
Collaborators
Source
Children's Hospital & Research Center Oakland
Oversight Info
Has Dmc
Yes
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.
Overall Status
Completed
Start Date
2004-06-01
Completion Date
2008-01-01
Primary Completion Date
2007-09-01
Phase
Phase 2
Study Type
Interventional
Primary Outcome
Measure |
Time Frame |
|
Gardos Channel Activity |
12 weeks after randomization |
|
Nitric Oxide |
12 weeks after randomization |
|
Mean Corpuscular Hemoglobin Concentration |
12 weeks after randomization |
Secondary Outcome
Measure |
Time Frame |
|
Soluble Vascular Cell Adhesion Molecule |
12 weeks after randomization |
|
8-iso-PGF2a |
12 weeks after randomization |
|
Endothelin-1 |
12 weeks after randomization |
|
Fetal Hemoglobin |
12 weeks after randomization |
Enrollment
128
Condition
Intervention
Intervention Type
Drug
Intervention Name
Description
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.
Arm Group Label
Low Dose
High Dose
Intervention Type
Drug
Intervention Name
Description
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.
Arm Group Label
Placebo
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
Gender
All
Minimum Age
5 Years
Maximum Age
N/A
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
|
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) |
|
Lennette Benjamin, MD |
Principal Investigator |
Montefiore Medical Center |
|
Mary Fabry, MD |
Principal Investigator |
Albert Einstein College of Medicine, Inc. |
|
Thomas Moulton, MD |
Principal Investigator |
Children's Hospital of Montefiore |
|
Kim Smith-Whitley, MD |
Principal Investigator |
Children's Hospital of Philadelphia |
|
Laura DeCastro, MD |
Principal Investigator |
Duke University |
|
Kenneth Ataga, MD |
Principal Investigator |
University of North Carolina, Chapel Hill |
|
Samir K. Ballas, MD |
Principal Investigator |
Thomas Jefferson University |
|
Sal Bertalone, MD |
Principal Investigator |
Norton Healthcare |
|
Carlton Dampier, MD |
Principal Investigator |
St. Christopher's Childrens Hospital |
|
William Mentzer, MD |
Principal Investigator |
University of California, San Francisco |
|
Winfred Wang, MD |
Principal Investigator |
St. Jude's Childrens Research Hospital |
|
Ulrike Reiss, MD |
Principal Investigator |
St. Jude Children's Research Hospital |
|
Cynthia Rutherford, MD |
Principal Investigator |
Children's Medical Center Dallas |
|
Kathryn Hassell, MD |
Principal Investigator |
University of Colorado, Denver |
|
Joan Parkhurst Cain, MD |
Principal Investigator |
Children's Hospital of Oklahoma |
Location
Facility |
|
Children's Hospital of Oakland and Research Institute Oakland California 94609 United States |
|
University of California - San Francisco San Francisco California 94143 United States |
|
University of Colorado at Denver and Health Sciences Center--Sickle Cell Treatment and Research Center Denver Colorado 80262 United States |
|
Kosair Children's Hospital Louisville Kentucky 40202 United States |
|
Boston Medical Center Boston Massachusetts 02118 United States |
|
University of Mississippi Medical Center (Adult) Jackson Mississippi 39215 United States |
|
University of Mississippi Medical Center (Pediatric) Jackson Mississippi 39215 United States |
|
Montefiore Medical Center Bronx New York 10463 United States |
|
Children's Hospital of Montefiore Bronx New York 10467 United States |
|
University of North Carolina at Chapel Hill Chapel Hill North Carolina 27599 United States |
|
Duke University Medical Center Durham North Carolina 27710 United States |
|
Children's Hospital of Oklahoma Oklahoma City Oklahoma 73104 United States |
|
Thomas Jefferson University Philadelphia Pennsylvania 19107 United States |
|
St. Christopher's Children's Research Hospital Philadelphia Pennsylvania 19134 United States |
|
Children's Hospital of Philadelphia Philadelphia Pennsylvania 19444 United States |
|
St. Jude Children's Research Hospital Memphis Tennessee 38105 United States |
|
Children's Medical Center of Dallas Dallas Texas 75390 United States |
Location Countries
Country
United States
Verification Date
2009-06-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Name Title
Lori Styles/Principal Investigator
Organization
Childrens Hospital of Oakland and Research Institute
Keywords
Has Expanded Access
No
Condition Browse
Secondary Id
U54HL070587-04
Number Of Arms
3
Arm Group
Arm Group Label
Low Dose
Arm Group Type
Active Comparator
Description
0.05 g/kg/day Arginine
Arm Group Label
High Dose
Arm Group Type
Active Comparator
Description
0.10 g/kg/day Arginine
Arm Group Label
Placebo
Arm Group Type
Placebo Comparator
Description
No Arginine
Firstreceived Results Date
N/A
Acronym
Arginine
Firstreceived Results Disposition Date
N/A
Study Design Info
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Study First Submitted
August 6, 2007
Study First Submitted Qc
August 6, 2007
Study First Posted
August 8, 2007
Last Update Submitted
February 28, 2017
Last Update Submitted Qc
February 28, 2017
Last Update Posted
March 29, 2017
Results First Submitted
February 23, 2009
Results First Submitted Qc
June 19, 2009
Results First Posted
August 4, 2009
ClinicalTrials.gov processed this data on August 28, 2018
Conditions
Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov,
conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.