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PURPOSE
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.
CONDITION: SICKLE CELL ANEMIA
INTERVENTION AGENT: L-ARGININE
TOTAL ENROLLMENT: 96 HUMAN SUBJECTS
PHASE: PHASE II – ARGININE vs PLACEBO
Study Type: Interventional
Study Design: Treatment, Randomized, Double-Blind, Placebo Control,
Parallel Assignment, Safety/Efficacy Study
Number of arms in study: 3
Official Title: Arginine Supplementation in Sickle Cell
Anemia: Physiological and Prophylactic Effects
Primary Outcome Measures: NO levels, Gardos channel activity, and
red blood cell density measurements. Time Frame: Measured at Weeks
4, 8, and 12.
Secondary
Outcome Measures:
| • |
Soluble
vascular cell adhesion molecule (sVCAM), nitrotyrosine, 8-iso-PGF2a,
ektacytomotry, endothelial-1, fetal hemoglobin (HbF), and
echocardiogram results [Time Frame: Measured at Weeks 4, 8,
and 12] |
| •
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Number
of hospitalizations, number of emergency department visits,
and pain medication use [Time Frame: Measured at Weeks 4,
8, and 12] |
Further study details as provided by National Heart, Lung, and Blood
Institute (NHLBI):
| Arms |
Assigned
Interventions |
| Low
Dose: Active Comparator 0.05 g/kg/day |
Drug:
Arginine |
| High
Dose: Active Comparator 0.10 g/kg/day |
Drug:
Arginine |
| Placebo:
Placebo Comparator |
Placebo
|
Eligibility
Ages Eligible for Study:
5 Years and above
Genders Eligible for Study: Both 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 |
Arginine
Treatment of Acute Chest Syndrome (Pneumonia) in Sickle Cell Disease
Patients
Conditions: Anemia, Sickle Cell; Pneumonia
PATENTS
FILED WITH UNITED STATES PTO FOR L-ARGININE TREATMENT IN SICKLE
CELL ANEMIA & THALASSEMIA:
Allen, Ann de Wees
Research Team: Clair Francomano, M.D., Randall Maxey, M.D. PhD.,
Thalassemia
(Cooley's Anemia) Clinical Research Network (TCRN)
Conditions: Anemia, Cooley's; Beta-Thalassemia; Hematologic Diseases;
Thalassemia; Osteoporosis; Iron Overload; Hypertension, Pulmonary
Effects
of L-Arginine Supplementation in Adults With Moderate to Severe
Asthma
Condition: Asthma
Role
of Nitric Oxide Scavenging by Plasma Hemoglobin and Identification
of Hemolysis-Associated Pulmonary Hypertension in Malaria
Conditions: Malaria; Pulmonary Hypertension
Arginine
Malaria Trial: Study of Adjunctive Arginine in Falciparum Malaria
Condition: Malaria, Falciparum
The
Short Term Safety and Efficacy of Inhaled L-Arginine in Patients
With Cystic Fibrosis
Condition: Cystic Fibrosis
Treatment
of Alcohol-Related Hepatitis With Arginine
Condition: Alcoholic Hepatitis
Arginine
Feeding: a Novel Strategy to Improve Protein Metabolism in Cancer
and the Response to Surgery
Condition: Protein Metabolism
L-Arginine
Metabolism in Essential Hypertension
Condition: Essential Hypertension
Study
of Arginine Metabolism and Nitric Oxide Formation in Relation to
Glutamine Supply in Severely Burned Patients.
Condition: Burn Injury
Nitric
Oxide (NO) Donors and Inhibitors Study: Study to Evaluate L-Arginine
and Aminoguanidine in Asthmatic Subjects
Condition: Asthma
Phase
II Randomized Trial of Arginine Butyrate Plus Standard Local Therapy
in Patients With Refractory Sickle Cell Ulcers
Conditions: Skin Ulcers; Sickle Cell Anemia
L-Arginine
Supplements in Treating Women Who Are Cancer Survivors
Conditions: Sexual Dysfunction and Infertility; Sexuality and Reproductive
Issues; Unspecified Adult Solid Tumor, Protocol Specific
NO
Donors and Inhibitors to Study Imbalance of Nitrogen Stress and
Antioxidant Defense in COPD
Conditions: Healthy Volunteers (Non-Smoker); Healthy Volunteers
(Smoker); Chronic Obstructive Pulmonary Disease
Nitric
Oxide (NO) Activity and Diabetic Nephropathy
Condition: Diabetic Nephropathies
Role of Nitric Oxide in Cirrhosis: Relationship With Systemic Hemodynamics,
Renal Function, Vasoactive Systems and Endotoxemia
Conditions: Cirrhosis; Liver Cirrhosis
A
Study Investigating a New, Oral Growth Hormone Secretagogue (GHS)(ARD-07)
as a Growth Hormone (GH) Stimulation Test
Conditions: Hypopituitarism; Hypothalamic Disease
Sexually
Dimorphic Effects of GHRH in Adult Growth Hormone Testing
Condition: Growth Hormone Deficiency
Treatment
for Growth Failure in Patients With X-Linked Severe Combined Immunodeficiency:
Phase 2 Study of Insulin-Like Growth Factor-1
Conditions: Growth Failure; X-Linked Severe Combined Immunodeficiency
(XSCID); Growth Hormone Resistence
Nutritional
Effect of an Amino Acid Mixture on Lean Body Mass (LBM) in Post-Bariatric
Surgery Patients
Conditions: Obesity; Post-Gastric Bypass
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