Safety and Efficacy of Sodium Nitrite in Sickle Cell Disease

This study has been terminated.
Sponsor:
Collaborator:
Hope Pharmaceuticals
Information provided by (Responsible Party):
Thomas Coates, Children's Hospital Los Angeles
ClinicalTrials.gov Identifier:
NCT01033227
First received: December 15, 2009
Last updated: June 11, 2012
Last verified: June 2012
  Purpose

This study will determine if administration of sodium nitrite is safe and can improve small vessel blood flow and tissue oxygenation when given as an additional treatment in patients with acute vaso-occlusive crisis (pain crisis) associated with sickle cell disease.


Condition Intervention Phase
Sickle Cell Disease
Drug: sodium nitrite injection, usp
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Safety and Efficacy Evaluation of Sodium Nitrite Injection for the Treatment of Vaso-Occlusive Crisis Associated With Sickle Cell Disease

Resource links provided by NLM:


Further study details as provided by Children's Hospital Los Angeles:

Primary Outcome Measures:
  • Per the protocol, safety assessments will include physical examinations, vital signs, clinical laboratory tests, ECG, methemoglobin concentration, and reported AEs. [ Time Frame: Every 8 hours after initiation of sodium nitrite infusion ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Adolescent Pediatric Pain Tool, total narcotic analgesic consumption, time between randomization & discharge, near infrared spectroscopy, serum LDH, reticulocyte count, plasma hemoglobin [ Time Frame: Every 8 hours after initiation of sodium nitrite infusion ] [ Designated as safety issue: No ]

Enrollment: 5
Study Start Date: December 2009
Estimated Study Completion Date: June 2012
Estimated Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: No drug Drug: sodium nitrite injection, usp
Sodium nitrite injection, USP will be administered in blocks of six subjects (3 sodium nitrite and 3 no drug). A total of five dose levels are planned, pending safety starting. Drug will be given by continuous infusion infusion for 48 hours starting at 6 nmol/min/kg (10% of the maximal tolerated dose).
Experimental: Sodium nitrite injection, USP
Administration if sodium nitrite injection, USP
Drug: sodium nitrite injection, usp
Sodium nitrite injection, USP will be administered in blocks of six subjects (3 sodium nitrite and 3 no drug). A total of five dose levels are planned, pending safety starting. Drug will be given by continuous infusion infusion for 48 hours starting at 6 nmol/min/kg (10% of the maximal tolerated dose).

Detailed Description:

Nitric oxide (NO) is a naturally occuring chemical that relaxes blood vessels and helps improve blood flow.

The pain associated with vaso-occlusive crisis (pain crisis) in sickle cell disease is caused in part by lack of oxygen and increased tissue acid because blood flow is blocked by stiff sickle red cells. Administration of sodium nitrite should generate nitric oxide in this area of hypoxia and acidosis and improve blood flow.

  Eligibility

Ages Eligible for Study:   8 Years to 23 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Subjects meeting all of the following criteria will be considered for admission to the study:

  1. Male or female subject aged between 8 and 23 years of age; only patients up to the age of 23 will be studied at Childrens Hospital Los Angeles
  2. Electrophoretic diagnosis of sickle cell disease;
  3. Sudden onset of acute pain involving >=1 sites typical of vaso-occlusive crisis (Vaso-occlusive crisis is defined as acute, severe pain in the extremities, chest, abdomen, or back that can not be explained by other complications of sickle cell disease or by a cause other than sickle cell disease.);
  4. Severe pain requiring parenteral analgesics and hospitalization.
  5. Informed consent obtained from a legal representative or from subjects 18 years of age or older before enrollment;
  6. Being willing and able to be followed for at least 30 days for evaluation.

Exclusion Criteria:

Subjects presenting with any of the following will not be included in the study:

  1. Clinically significant bleeding;
  2. Current drug abuse or participation in methadone program;
  3. Episode of pain requiring hospitalization within 2 weeks prior to current admission;
  4. Other complications of sickle cell disease including cerebrovascular accident, pulmonary hypertension, or seizure;
  5. Pregnancy (confirmed by a serum human chorionic gonadotropin pregnancy test) or breast feeding;
  6. Blood pressure less than 25th percentile for the subject's age and sex on admission or at the time of screening;
  7. Methemoglobinemia >3%;
  8. Anemia with hemoglobin level less than 6 g/dL;
  9. Red blood cell G6PD deficiency, by laboratory testing prior to enrollment;
  10. History of allergy to nitrites or allergy to other substances characterized by dyspnea and cyanosis;
  11. Treatment with allopurinol, a medication that could interfere with nitrite metabolism, within the past 30 days before screening;
  12. Treatment with any investigational drug within the past 30 days;
  13. Significant acute or chronic concomitant diseases (including renal, hepatic, cardiovascular, pulmonary, or oncologic disease, sepsis, pulmonary edema, pulmonary embolism) that would be inconsistent with survival for at least 6 months;
  14. Any subject judged by the clinical investigator or study manager to be inappropriate for the study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01033227

Locations
United States, California
Childrens Hospital Los Angeles
Los Angeles, California, United States, 90027
Sponsors and Collaborators
Children's Hospital Los Angeles
Hope Pharmaceuticals
  More Information

Publications:

Responsible Party: Thomas Coates, Hematology Division Head, Children's Hospital Los Angeles
ClinicalTrials.gov Identifier: NCT01033227     History of Changes
Other Study ID Numbers: SN-SC-02-01
Study First Received: December 15, 2009
Last Updated: June 11, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Children's Hospital Los Angeles:
sickle cell disease
sickle cell anemia
pain crisis
nitric oxide
nitrite
vaso occlusive crisis
pain medication
sickled cells
blood flow
microcirculation

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on April 16, 2014