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A Pilot Study of N-acetylcysteine in Patients With Sickle Cell Disease (NACinSCD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01800526
Recruitment Status : Enrolling by invitation
First Posted : February 27, 2013
Last Update Posted : July 11, 2018
University of Washington
Information provided by (Responsible Party):
Barbara A. Konkle, M.D., Bloodworks

Brief Summary:

Part 1: A pilot study in patients with homozygous S (HbSS) or hemoglobin S with beta zero thalassemia(HbS-βo thalassemia), with the aim of examining the effect of intravenous NAC treatment on plasma VWF parameters and measures of redox and RBC function.

Part 2: A pilot study in patients with sickle cell disease admitted to the hospital in vaso-occlusive crisis to determine the effects of NAC infusions on plasma VWF parameters and measures of redox and RBC function, and on measures of pain and hospital length of stay.

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Sickle Cell Anemia Drug: N-Acetylcysteine Phase 1 Phase 2

Detailed Description:

Two primary processes dominate the complications associated with sickle cell disease (SCD): vasoocclusion and hemolysis. The plasma and vessel wall adhesive protein von Willebrand factor (VWF) is thought to be involved in both of these processes, so strategies aimed at reducing its secretion or reactivity, which could decrease complications in patients with SCD, are being tested.

Based on prior studies, N-acetylcysteine (NAC) treatment may decrease VWF activity in patients with SCD and may be a useful adjunctive treatment in this disorder.

Part 1 enrolls stable outpatients with homozygous S (HbSS) or hemoglobin S with beta zero thalassemia (HbS-βo thalassemia), with the aim of examining the effect of NAC treatment on VWF parameters, measures of oxidation and RBC fragments. Patients receive IV NAC first at 150 mg/kg over 8 hours and if tolerated, at a later date at 300 mg/kg over 8 hours in the University of Washington Clinical Research Center. Blood is collected for laboratory assessment. Subjects are later offered enrollment in an oral phase.

Part 2, patients with a history of vaso-occlusive crisis (VOC) are approached in the outpatient setting to discuss the study. When admitted for VOC, subjects receive NAC as an IV infusion75 mg/kg every 6 hours for up to 5 days. Blood for laboratory assays are collected each morning and pain assessment is performed prior to and following each NAC infusion.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study of N-acetylcysteine in Patients With Sickle Cell Disease
Actual Study Start Date : March 2013
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : March 2019

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Oral N-acetylcysteine (NAC)
Eligible subjects who did not participate in Intravenous NAC or subjects who are at least 4 weeks after participation in Intravenous NAC, will be given Oral NAC at a dose of 2400mg daily, in two equally divided doses, for 4 weeks. Subjects will have blood drawn prior to beginning the phase and weekly for 4 weeks. At each visit interim medical events and adverse events will be collected.
Drug: N-Acetylcysteine
Oral and Intravenous administration of NAC

Experimental: Intravenous N-acetylcysteine (NAC)

For part 1, Eligible subjects who did not participate in Oral NAC or subjects at least 4 weeks after oral NAC will receive IV NAC 150 mg/kg over 8 hours. At least four weeks after the first infusion, the subject will receive IV NAC 300 mg/kg over 8 hours.

For part 2, Eligible subjects with sickle cell disease and hospitalization for VOC within the past 2 years, who now present in VOC will be enrolled. Subjects will receive IV NAC 75 mg/kg over 1 hour every 6 hours for 5 days or discharge, whichever occurs earlier.

Drug: N-Acetylcysteine
Oral and Intravenous administration of NAC

Primary Outcome Measures :
  1. Laboratory measures of VWF activity [ Time Frame: Part 1, Prior to during and following one day infusion or during oral administration; Part 2, daily during infusion and just following infusion completion ]
    To determine if NAC, given intravenously as a one day infusion, orally as an outpatient or during hospitalization for VOC has an effect on VWF level or function.

Secondary Outcome Measures :
  1. Laboratory measures of red blood cell hemolysis and oxidation [ Time Frame: Red blood cell (RBC) lab measures will be drawn prior to infusion, at the end of the infusion, 1 and 3 days following the end of the infusion, once a week during oral administration, and daily during hospitalization ]
    To determine effects of NAC treatment on laboratory markers of sickle cell disease by measuring a) lactate dehydrogenase (LDH) B) reticulocyte count, and c) percent dense cells and on oxidation by measuring RBC glutathione.

  2. Adverse events during and following NAC administration [ Time Frame: Adverse events will be measured from time of consent to completion of study, with particular attention to times around and during administration. ]
    To assess safety by evaluating subjects for adverse events during and at time points following administration.

  3. Pain during VOC [ Time Frame: Before and following each NAC infusion while hospitalized ]
    Pain will be measured using visual analog scale and numerical rating scale at study entry, and before and at completion of each infusion during hospitalization for VOC

  4. Use of pain medications in morphine equivalents [ Time Frame: Morphine equivalents for the hospitalization during which NAC was administered compared to past VOC admissions ]
    Data on morphine equivalents administered during the study hospitalization will be compared to those of past admissions.

  5. Hospital length of stay (LOS) [ Time Frame: Days of hospitalization during study compared to past hospitalizations for VOC ]
    LOS will be calculated by days of hospitalization when study drug is administered compared to past LOS for VOC admissions

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Age >= 18 years of age
  2. Diagnosis of homozygous sickle cell (SS) or S-beta thalassemia with at least two episodes of vaso-occlusive crises (VOC) requiring narcotics in each of the past 2 years. For part 2 can include hemoglobin SC disease.
  3. For females of reproductive age, use of contraception and negative pregnancy test

Exclusion Criteria:

  1. An additional hematologic diagnosis
  2. Hemoglobin (Hgb) < 7gm/dL for part 1, < 6 gm/dL for part 2.
  3. Asthma requiring medication
  4. Liver function tests [alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (BilliT) > three times upper normal limit for Part 1.
  5. Chronic transfusion therapy, or transfusion within 2 months of enrollment. For part 2 anticipated need for simple or exchange transfusion during hospitalization.
  6. VOC requiring narcotic therapy within the prior week or requiring hospitalization with discharge < 2 weeks prior to study enrollment for Part 1, for part 2 admission for VOC within 30 days.
  7. Pregnancy or nursing
  8. Receiving another investigational drug
  9. Known allergy to NAC
  10. Per subject's physician not medically stable enough to participate
  11. Taking nitroglycerin, carbamazepine, or phosphodiesterase 5 (PDE5) inhibitors
  12. Abnormal baseline coagulation tests (> 1.5 times normal limits)
  13. Platelets <150,000/microliter for Part 1.
  14. For part 2, already enrolled in study twice.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01800526

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United States, Washington
University of Washington
Seattle, Washington, United States, 98106
Sponsors and Collaborators
University of Washington
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Principal Investigator: Barbara A Konkle, M.D. Univ. of Washington/Bloodworks Northwest

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Responsible Party: Barbara A. Konkle, M.D., Director, Clinical and Translational Research, Bloodworks Identifier: NCT01800526     History of Changes
Other Study ID Numbers: 117090
First Posted: February 27, 2013    Key Record Dates
Last Update Posted: July 11, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data will be published at end of study and data made available to outside investigators after results are published by investigators
Keywords provided by Barbara A. Konkle, M.D., Bloodworks:
Sickle Cell Disease
Sickle Cell Anemia
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Hematologic Diseases
Genetic Diseases, Inborn
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Antiviral Agents
Anti-Infective Agents
Respiratory System Agents
Free Radical Scavengers
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs