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Sickle Cell DiseasePhase 1/2NCT01033227

Safety and Efficacy of Sodium Nitrite in Sickle Cell Disease

A Phase 1/2 study testing sodium nitrite injection, usp in people with Sickle Cell Disease, run by Children's Hospital Los Angeles at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 8 to 23 years
Conditions the study is for
Sickle Cell Disease
What is being tested?
sodium nitrite injection, usp
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
1 siteUnited States
Study dates
Dec 2009to Jun 2012
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 8 to 23 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.

Who cannot join

  • 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;
Show all 15Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Childrens Hospital Los Angeles

    Los Angeles, California, 90027

Other trials in United States

About this study

Official title: 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.

Read the 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.

Being tested
sodium nitrite injection, usp
Keywords
sickle cell disease, sickle cell anemia, pain crisis, nitric oxide, nitrite, vaso occlusive crisis, pain medication, sickled cells, blood flow, microcirculation
Medical subject headings
Anemia, Sickle Cell, Vaso-Occlusive Crises

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • sodium nitrite injection, uspDrug

    Also called sodium nitrite

    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).

Study groups in NCT01033227
Study groupRoleWhat they receive
No drugNo interventionNo study drug administered
Sodium nitrite injection, USPExperimentalAdministration if sodium nitrite injection, USP
Receives: Drug: sodium nitrite injection, usp

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 48 hours from start of infusion

Secondary outcomes (1)
  1. Secondary End Point

    1. reduced the duration and intensity of pain; b) reduced total narcotic analgesic consumption; and c) reduced length of hospitalization.

    Measured: 48 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Dec 2009 (estimated)
  2. Study startDec 2009
  3. Primary completionJun 2012
  4. Study completionJun 2012

Why it stopped: Low enrollment

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01033227
Sponsor's protocol ID
SN-SC-02-01
Status last verified
Sep 2017
First submitted
15 Dec 2009
Last updated
17 Oct 2017
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Wood KC, Hsu LL, Gladwin MT. Sickle cell disease vasculopathy: a state of nitric oxide resistance. Free Radic Biol Med. 2008 Apr 15;44(8):1506-28. doi: 10.1016/j.freeradbiomed.2008.01.008. Epub 2008 Jan 26.

    PubMed 18261470
  • Mack AK, McGowan Ii VR, Tremonti CK, Ackah D, Barnett C, Machado RF, Gladwin MT, Kato GJ. Sodium nitrite promotes regional blood flow in patients with sickle cell disease: a phase I/II study. Br J Haematol. 2008 Sep;142(6):971-8. doi: 10.1111/j.1365-2141.2008.07259.x. Epub 2008 Jul 11.

    PubMed 18671702
  • Lundberg JO, Weitzberg E. Nitrite reduction to nitric oxide in the vasculature. Am J Physiol Heart Circ Physiol. 2008 Aug;295(2):H477-8. doi: 10.1152/ajpheart.00611.2008. Epub 2008 Jun 27. No abstract available.

    PubMed 18586886
  • Hachiya T, Blaber AP, Saito M. Near-infrared spectroscopy provides an index of blood flow and vasoconstriction in calf skeletal muscle during lower body negative pressure. Acta Physiol (Oxf). 2008 Jun;193(2):117-27. doi: 10.1111/j.1748-1716.2007.01827.x. Epub 2007 Dec 19.

    PubMed 18162057
  • Cappellini MD, Fiorelli G. Glucose-6-phosphate dehydrogenase deficiency. Lancet. 2008 Jan 5;371(9606):64-74. doi: 10.1016/S0140-6736(08)60073-2.

    PubMed 18177777
  • Villagra J, Shiva S, Hunter LA, Machado RF, Gladwin MT, Kato GJ. Platelet activation in patients with sickle disease, hemolysis-associated pulmonary hypertension, and nitric oxide scavenging by cell-free hemoglobin. Blood. 2007 Sep 15;110(6):2166-72. doi: 10.1182/blood-2006-12-061697. Epub 2007 May 29.

    PubMed 17536019
  • Vanin AF, Bevers LM, Slama-Schwok A, van Faassen EE. Nitric oxide synthase reduces nitrite to NO under anoxia. Cell Mol Life Sci. 2007 Jan;64(1):96-103. doi: 10.1007/s00018-006-6374-2.

    PubMed 17160351
  • Kato GJ, McGowan V, Machado RF, Little JA, Taylor J 6th, Morris CR, Nichols JS, Wang X, Poljakovic M, Morris SM Jr, Gladwin MT. Lactate dehydrogenase as a biomarker of hemolysis-associated nitric oxide resistance, priapism, leg ulceration, pulmonary hypertension, and death in patients with sickle cell disease. Blood. 2006 Mar 15;107(6):2279-85. doi: 10.1182/blood-2005-06-2373. Epub 2005 Nov 15.

    PubMed 16291595
  • Ferreira LF, Harper AJ, Townsend DK, Lutjemeier BJ, Barstow TJ. Kinetics of estimated human muscle capillary blood flow during recovery from exercise. Exp Physiol. 2005 Sep;90(5):715-26. doi: 10.1113/expphysiol.2005.030189. Epub 2005 May 20.

    PubMed 15908509
  • Raj A, Bertolone SJ, Mangold S, Edmonds HL Jr. Assessment of cerebral tissue oxygenation in patients with sickle cell disease: effect of transfusion therapy. J Pediatr Hematol Oncol. 2004 May;26(5):279-83. doi: 10.1097/00043426-200405000-00004.

    PubMed 15111778
  • Gladwin MT, Crawford JH, Patel RP. The biochemistry of nitric oxide, nitrite, and hemoglobin: role in blood flow regulation. Free Radic Biol Med. 2004 Mar 15;36(6):707-17. doi: 10.1016/j.freeradbiomed.2003.11.032.

    PubMed 14990351
  • Gladwin MT, Lancaster JR Jr, Freeman BA, Schechter AN. Nitric oxide's reactions with hemoglobin: a view through the SNO-storm. Nat Med. 2003 May;9(5):496-500. doi: 10.1038/nm0503-496. No abstract available.

    PubMed 12724752
  • Cosby K, Partovi KS, Crawford JH, Patel RP, Reiter CD, Martyr S, Yang BK, Waclawiw MA, Zalos G, Xu X, Huang KT, Shields H, Kim-Shapiro DB, Schechter AN, Cannon RO 3rd, Gladwin MT. Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation. Nat Med. 2003 Dec;9(12):1498-505. doi: 10.1038/nm954. Epub 2003 Nov 2.

    PubMed 14595407
  • Gladwin MT, Schechter AN, Shelhamer JH, Ognibene FP. The acute chest syndrome in sickle cell disease. Possible role of nitric oxide in its pathophysiology and treatment. Am J Respir Crit Care Med. 1999 May;159(5 Pt 1):1368-76. doi: 10.1164/ajrccm.159.5.9810094. No abstract available.

    PubMed 10228097
  • Lundberg JO, Gladwin MT, Ahluwalia A, Benjamin N, Bryan NS, Butler A, Cabrales P, Fago A, Feelisch M, Ford PC, Freeman BA, Frenneaux M, Friedman J, Kelm M, Kevil CG, Kim-Shapiro DB, Kozlov AV, Lancaster JR Jr, Lefer DJ, McColl K, McCurry K, Patel RP, Petersson J, Rassaf T, Reutov VP, Richter-Addo GB, Schechter A, Shiva S, Tsuchiya K, van Faassen EE, Webb AJ, Zuckerbraun BS, Zweier JL, Weitzberg E. Nitrate and nitrite in biology, nutrition and therapeutics. Nat Chem Biol. 2009 Dec;5(12):865-9. doi: 10.1038/nchembio.260.

    PubMed 19915529

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing sodium nitrite injection, usp in people with Sickle Cell Disease, run by Children's Hospital Los Angeles at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 17 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Feb 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

48 Hour Sodium Nitrite Infusion Safety as Determined by Number of Participants With No Adverse Events (time frame: 48 hours from start of infusion). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01033227, which also lists 15 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Oct 2017.

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