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

This study is enrolling participants by invitation only.
University of Washington
Information provided by (Responsible Party):
Barbara A. Konkle, M.D., Puget Sound Blood Center Identifier:
First received: January 21, 2013
Last updated: October 10, 2014
Last verified: October 2014

Two primary processes dominate the complications associated with sickle cell disease (SCD): vasoocclusion and hemolysis. Vasoocclusion is very likely to account for the tissue infarction and pain associated with the disease, while hemolysis liberates hemoglobin into the plasma where it scavenges nitric oxide (NO), producing vascular complications such as pulmonary hypertension and skin ulcers. 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.

This is a pilot study in patients with hemoglobin 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. As a first step, the investigators will examine whether intravenous or oral administration of NAC, in doses used to treat other conditions, changes VWF content, activity, multimer size, or extent of oxidation. In prior studies, investigators have shown that a number of patients followed in the sickle cell clinic at the University of Washington have ultralarge VWF multimers and high VWF:total activity (TA). Only patients with elevated VWF are eligible for this pilot study.

Condition Intervention Phase
Sickle Cell Disease
Sickle Cell Anemia
Drug: N-Acetylcysteine
Phase 0

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of N-acetylcysteine in Patients With Sickle Cell Disease

Resource links provided by NLM:

Further study details as provided by Puget Sound Blood Center:

Primary Outcome Measures:
  • Laboratory measures of VWF activity [ Time Frame: Lab assays of VWF activity will be assessed in blood drawn prior to infusion, at the end of the infusion, 1 and 3 days following the end of the infusion and once a week during oral administration. Percent changes in activity over time will be reported. ] [ Designated as safety issue: No ]
    To determine if NAC, given intravenously as a one day infusion, or orally over a period of 4 weeks, effectively decreases VWF levels, VWF Total Activity, ULVWF multimers, VWF functions (ristocetin- and shear-induced platelet agglutination), and the extent of VWF methionine oxidation in the A1-A2-A3 region, at different time points during and following administration.

Secondary Outcome Measures:
  • 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 and once a week during oral administration. Percent changes in measurements will be reported over time. ] [ Designated as safety issue: No ]
    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.

  • Adverse events during and following NAC administration [ Time Frame: Adverse events will be collected throughout the study and specifically during infusion, one and 3 days after infusion and once per week during study period. ] [ Designated as safety issue: Yes ]
    To assess safety by evaluating subjects for adverse events including vaso-occlusive crises and bleeding symptoms during and at time points following administration.

Estimated Enrollment: 5
Study Start Date: March 2013
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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. Women will have a pregnancy test at each visit. Subjects will maintain a diary. 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)
Eligible subjects who did not participate in Oral NAC or subjects who are at least 4 weeks after participation in Oral NAC will be administered NAC by IV infusion at 75mg/Kg loading dose over 60 minutes, followed by a 75mg/Kg dose by continuous infusion over 7 hours. At least four weeks after the first infusion, and if the subject tolerated the first infusion, the subject will receive NAC by IV infusion at a 150mg/Kg loading dose over 60 minutes followed by a 150mg/Kg dose over 7 hours. Blood will be drawn prior to the infusion, at the end of the loading dose, at the conclusion of the infusion, and 24 and 72 hours post infusion. Vital signs will be monitored and adverse events collected. Females will have a negative pregnancy test prior to starting the infusion.
Drug: N-Acetylcysteine
Oral and Intravenous administration of NAC


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Age >= 18 years of age
  2. Diagnosis of homozygous sickle cell (SS) or S-betao thalassemia with at least two episodes of vaso-occlusive crises (VOC) requiring narcotics in each of the past 2 years.
  3. Ultra Low Von Willebrand Factor (ULVWF) multimers on agarose gel analysis of patient's plasma
  4. For females of reproductive age, use of contraception and negative pregnancy test
  5. VWF antigen elevated to >150%

Exclusion Criteria:

  1. An additional hematologic diagnosis
  2. Hemoglobin (Hgb) < 7gm/dL
  3. Asthma
  4. Liver function tests [alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (BilliT) > three times upper normal limit
  5. Chronic transfusion therapy, or transfusion within 2 months of enrollment
  6. VOC requiring narcotic therapy within the prior week or requiring hospitalization with discharge < 2 weeks prior to study enrollment
  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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01800526

United States, Washington
University of Washington
Seattle, Washington, United States, 98106
Sponsors and Collaborators
Puget Sound Blood Center
University of Washington
Principal Investigator: Barbara A Konkle, M.D. Univ. of Washington/Puget Sound Blood Center
  More Information

No publications provided

Responsible Party: Barbara A. Konkle, M.D., Director, Clinical and Translational Research, Puget Sound Blood Center Identifier: NCT01800526     History of Changes
Other Study ID Numbers: 117090
Study First Received: January 21, 2013
Last Updated: October 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Puget Sound Blood Center:
Sickle Cell Disease
Sickle Cell Anemia

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia, Hemolytic
Anemia, Hemolytic, Congenital
Genetic Diseases, Inborn
Hematologic Diseases
Anti-Infective Agents
Antiviral Agents
Free Radical Scavengers
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Respiratory System Agents
Therapeutic Uses processed this record on March 01, 2015