NCT00513617

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
128

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Jun 2004

Typical duration for phase_2

Geographic Reach
1 country

17 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2004

Completed
3.2 years until next milestone

First Submitted

Initial submission to the registry

August 6, 2007

Completed
2 days until next milestone

First Posted

Study publicly available on registry

August 8, 2007

Completed
24 days until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2007

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2008

Completed
1.6 years until next milestone

Results Posted

Study results publicly available

August 4, 2009

Completed
Last Updated

March 29, 2017

Status Verified

June 1, 2009

Enrollment Period

3.3 years

First QC Date

August 6, 2007

Results QC Date

February 23, 2009

Last Update Submit

February 28, 2017

Conditions

Anemia, Sickle Cell

Keywords

Sickle Cell DiseaseAnemiaNitric OxideVaso Occlusive EventsArginine Supplementation

Outcome Measures

Primary Outcomes (3)

  • Gardos Channel Activity

    Gardos channel activity: a calcium (Ca2+)-activated K+ channel

    12 weeks after randomization

  • Nitric Oxide

    Nitric oxide from plasma amino acids

    12 weeks after randomization

  • Mean Corpuscular Hemoglobin Concentration

    Mean corpuscular hemoglobin concentration as measured by an Advia machine

    12 weeks after randomization

Secondary Outcomes (4)

  • 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

Study Arms (3)

Low Dose

ACTIVE COMPARATOR

0.05 g/kg/day Arginine

Drug: Arginine

High Dose

ACTIVE COMPARATOR

0.10 g/kg/day Arginine

Drug: Arginine

Placebo

PLACEBO COMPARATOR

No Arginine

Drug: Placebo

Interventions

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.

High DoseLow Dose
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.

Placebo

Eligibility Criteria

Age5 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (17)

Children's Hospital of Oakland and Research Institute

Oakland, California, 94609, United States

Location

University of California - San Francisco

San Francisco, California, 94143, United States

Location

University of Colorado at Denver and Health Sciences Center--Sickle Cell Treatment and Research Center

Denver, Colorado, 80262, United States

Location

Kosair Children's Hospital

Louisville, Kentucky, 40202, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

University of Mississippi Medical Center (Adult)

Jackson, Mississippi, 39215, United States

Location

University of Mississippi Medical Center (Pediatric)

Jackson, Mississippi, 39215, United States

Location

Montefiore Medical Center

The Bronx, New York, 10463, United States

Location

Children's Hospital of Montefiore

The Bronx, New York, 10467, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Children's Hospital of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

St. Christopher's Children's Research Hospital

Philadelphia, Pennsylvania, 19134, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19444, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Children's Medical Center of Dallas

Dallas, Texas, 75390, United States

Location

Related Publications (1)

  • 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.

    PMID: 38775255DERIVED

MeSH Terms

Conditions

Anemia, Sickle CellAnemiaVaso-Occlusive Crises

Interventions

Arginine

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, CongenitalAnemia, HemolyticHematologic DiseasesHemic and Lymphatic DiseasesHemoglobinopathiesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Amino Acids, BasicAmino AcidsAmino Acids, Peptides, and ProteinsAmino Acids, DiaminoAmino Acids, Essential

Limitations and Caveats

Adult enrollment was slower than expected. Adult subjects were more likely than peds to drop-out due to SCD pain crisis. Higher doses of arginine (such as used in animal studies) were limited by number of daily pills required.

Results Point of Contact

Title
Karen Kesler, PhD
Organization
Rho Federal Systems Division
karen_kesler@rhoworld.com
919-408-8000

Study Officials

  • 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

  • Kim Smith-Whitley, MD

    Children's Hospital of Philadelphia

    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

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

August 6, 2007

First Posted

August 8, 2007

Study Start

June 1, 2004

Primary Completion

September 1, 2007

Study Completion

January 1, 2008

Last Updated

March 29, 2017

Results First Posted

August 4, 2009

Record last verified: 2009-06

Locations

US(17)