Safety and Efficacy of Sodium Nitrite in Sickle Cell Disease

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Safety and Efficacy Evaluation of Sodium Nitrite Injection for the Treatment of Vaso-Occlusive Crisis Associated With Sickle Cell Disease

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Drug: sodium nitrite injection, usp


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects meeting all of the following criteria will be considered for admission to the study: 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 Electrophoretic diagnosis of sickle cell disease; 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.); Severe pain requiring parenteral analgesics and hospitalization. Informed consent obtained from a legal representative or from subjects 18 years of age or older before enrollment; 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: Clinically significant bleeding; Current drug abuse or participation in methadone program; Episode of pain requiring hospitalization within 2 weeks prior to current admission; Other complications of sickle cell disease including cerebrovascular accident, pulmonary hypertension, or seizure; Pregnancy (confirmed by a serum human chorionic gonadotropin pregnancy test) or breast feeding; Blood pressure less than 25th percentile for the subject's age and sex on admission or at the time of screening; Methemoglobinemia >3%; Anemia with hemoglobin level less than 6 g/dL; Red blood cell G6PD deficiency, by laboratory testing prior to enrollment; History of allergy to nitrites or allergy to other substances characterized by dyspnea and cyanosis; Treatment with allopurinol, a medication that could interfere with nitrite metabolism, within the past 30 days before screening; Treatment with any investigational drug within the past 30 days; 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; Any subject judged by the clinical investigator or study manager to be inappropriate for the study.

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 23 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: No drug<br>No study drug administered | |
| Experimental: Sodium nitrite injection, USP<br>Administration if sodium nitrite injection, USP | Drug: sodium nitrite injection, usp<br>* 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).<br>* Other names: sodium nitrite;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 48 Hour Sodium Nitrite Infusion Safety as Determined by Number of Participants With No Adverse Events | The primary end points will be to determine if a) a 48-hour sodium nitrite infusion is tolerated without a decrease in mean arterial blood pressure by 15mmHg for greater than 2 hours or development of methemoglobin greater than 5% and b) a 48-hour sodium nitrite infusion is safe as determined by monitoring for adverse events | 48 hours from start of infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary End Point | a) reduced the duration and intensity of pain; b) reduced total narcotic analgesic consumption; and c) reduced length of hospitalization. | 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sickle cell disease, sickle cell anemia, pain crisis, nitric oxide, nitrite, vaso occlusive crisis, pain medication, sickled cells, blood flow, microcirculation