Safety and Efficacy of Sodium Nitrite in Sickle Cell Disease

September 15, 2017 updated by: Thomas Coates, Children's Hospital Los Angeles

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

5

Phase

  • Phase 2
  • Phase 1

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
      • Los Angeles, California, United States, 90027
        • Childrens Hospital Los Angeles

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

Ages Eligible for Study

8 years to 23 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

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: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: No drug
No study drug administered
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).
Other Names:
  • sodium nitrite

What is the study measuring?

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
Time Frame: 48 hours from start of infusion
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
Time Frame: 48 hours
a) reduced the duration and intensity of pain; b) reduced total narcotic analgesic consumption; and c) reduced length of hospitalization.
48 hours

Collaborators and Investigators

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

Sponsor

Children's Hospital Los Angeles

Collaborators

Hope Pharmaceuticals

Investigators

  • Principal Investigator: Thomas Coates, MD, Children's Hospital Los Angeles

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

December 1, 2009

Primary Completion (Actual)

June 1, 2012

Study Completion (Actual)

June 1, 2012

Study Registration Dates

First Submitted

December 15, 2009

First Submitted That Met QC Criteria

December 15, 2009

First Posted (Estimate)

December 16, 2009

Study Record Updates

Last Update Posted (Actual)

October 17, 2017

Last Update Submitted That Met QC Criteria

September 15, 2017

Last Verified

September 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SN-SC-02-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

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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