Effectiveness of Arginine as a Treatment for Sickle Cell Anemia (Arginine)

February 28, 2017 updated by: UCSF Benioff Children's Hospital Oakland

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
128

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Oakland, California, United States, 94609
        • Children's Hospital of Oakland and Research Institute
      • San Francisco, California, United States, 94143
        • University of California - San Francisco
    • Colorado
      • Denver, Colorado, United States, 80262
        • University of Colorado at Denver and Health Sciences Center--Sickle Cell Treatment and Research Center
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Kosair Children's Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Boston Medical Center
    • Mississippi
      • Jackson, Mississippi, United States, 39215
        • University of Mississippi Medical Center (Adult)
      • Jackson, Mississippi, United States, 39215
        • University of Mississippi Medical Center (Pediatric)
    • New York
      • Bronx, New York, United States, 10463
        • Montefiore Medical Center
      • Bronx, New York, United States, 10467
        • Children's Hospital of Montefiore
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina At Chapel Hill
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Children's Hospital of Oklahoma
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University
      • Philadelphia, Pennsylvania, United States, 19134
        • St. Christopher's Children's Research Hospital
      • Philadelphia, Pennsylvania, United States, 19444
        • Children's Hospital of Philadelphia
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • St. Jude Children's Research Hospital
    • Texas
      • Dallas, Texas, United States, 75390
        • Children's Medical Center of Dallas

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

5 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Low Dose
0.05 g/kg/day Arginine
Drug: Arginine
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.
Active Comparator: High Dose
0.10 g/kg/day Arginine
Drug: Arginine
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.
Placebo Comparator: Placebo
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Gardos Channel Activity
Time Frame: 12 weeks after randomization
Gardos channel activity: a calcium (Ca2+)-activated K+ channel
12 weeks after randomization
Nitric Oxide
Time Frame: 12 weeks after randomization
Nitric oxide from plasma amino acids
12 weeks after randomization
Mean Corpuscular Hemoglobin Concentration
Time Frame: 12 weeks after randomization
Mean corpuscular hemoglobin concentration as measured by an Advia machine
12 weeks after randomization

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Soluble Vascular Cell Adhesion Molecule
Time Frame: 12 weeks after randomization
Soluble vascular cell adhesion molecule (sVCAM) a vascular adhesion molecule
12 weeks after randomization
8-iso-PGF2a
Time Frame: 12 weeks after randomization
8-iso-PGF2a is a measure of lipid peroxidation and oxidative damage in vivo measured by enzyme immunoassay kit from Cayman chemical
12 weeks after randomization
Endothelin-1
Time Frame: 12 weeks after randomization
Endothelin-1 is a potent vasoconstrictor and pro-inflammatory agent which is elevated in SCD patients
12 weeks after randomization
Fetal Hemoglobin
Time Frame: 12 weeks after randomization
Fetal hemoglobin (HbF) as measured by the Advia machine
12 weeks after randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
UCSF Benioff Children's Hospital Oakland

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Lillian McMahon, MD, Boston Medical Center
  • Principal Investigator: Rathi Iyer, MD, University of Mississippi Medical Center (Pediatric)
  • Principal Investigator: Carolyn Bigelow, MD, University of Mississippi Medical Center (Adult)
  • Principal Investigator: Lennette Benjamin, MD, Montefiore Medical Center
  • Principal Investigator: Mary Fabry, MD, Albert Einstein College of Medicine
  • Principal Investigator: Thomas Moulton, MD, Children's Hospital of Montefiore
  • Principal Investigator: Laura DeCastro, MD, Duke University
  • Principal Investigator: Kenneth Ataga, MD, University of North Carolina, Chapel Hill
  • Principal Investigator: Samir K. Ballas, MD, Thomas Jefferson University
  • Principal Investigator: Sal Bertalone, MD, Norton Healthcare
  • Principal Investigator: Carlton Dampier, MD, St. Christopher's Childrens Hospital
  • Principal Investigator: William Mentzer, MD, University of California, San Francisco
  • Principal Investigator: Winfred Wang, MD, St. Jude's Childrens Research Hospital
  • Principal Investigator: Ulrike Reiss, MD, St. Jude Children's Research Hospital
  • Principal Investigator: Cynthia Rutherford, MD, Children's Medical Center Dallas
  • Principal Investigator: Kathryn Hassell, MD, University of Colorado, Denver
  • Principal Investigator: Joan Parkhurst Cain, MD, Children's Hospital of Oklahoma

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2004

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2007

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2008

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 6, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 6, 2007

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 8, 2007

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 29, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 28, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 485
  • U54HL070587-04 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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