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

This study is enrolling participants by invitation only.
Sponsor:
Collaborator:
University of Washington
Information provided by (Responsible Party):
Barbara A. Konkle, M.D., Bloodworks (Puget Sound Blood Center)
ClinicalTrials.gov Identifier:
NCT01800526
First received: January 21, 2013
Last updated: April 8, 2016
Last verified: April 2016
  Purpose

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 Intervention Phase
Sickle Cell Disease
Sickle Cell Anemia
Drug: N-Acetylcysteine
Phase 1
Phase 2

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 Bloodworks (Puget Sound Blood Center):

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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:
  • 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 ] [ 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 measured from time of consent to completion of study, with particular attention to times around and during administration. ] [ Designated as safety issue: Yes ]
    To assess safety by evaluating subjects for adverse events during and at time points following administration.

  • Pain during VOC [ Time Frame: Before and following each NAC infusion while hospitalized ] [ Designated as safety issue: No ]
    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

  • Use of pain medications in morphine equivalents [ Time Frame: Morphine equivalents for the hospitalization during which NAC was administered compared to past VOC admissions ] [ Designated as safety issue: No ]
    Data on morphine equivalents administered during the study hospitalization will be compared to those of past admissions.

  • Hospital length of stay (LOS) [ Time Frame: Days of hospitalization during study compared to past hospitalizations for VOC ] [ Designated as safety issue: No ]
    LOS will be calculated by days of hospitalization when study drug is administered compared to past LOS for VOC admissions


Estimated Enrollment: 20
Study Start Date: March 2013
Estimated Study Completion Date: August 2018
Estimated Primary Completion Date: December 2017 (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. 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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  4. For part 2, at least one prior admission for VOC at the University of Washington in past 2 years.

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.
  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 ClinicalTrials.gov identifier: NCT01800526

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

Responsible Party: Barbara A. Konkle, M.D., Director, Clinical and Translational Research, Bloodworks (Puget Sound Blood Center)
ClinicalTrials.gov Identifier: NCT01800526     History of Changes
Other Study ID Numbers: 117090 
Study First Received: January 21, 2013
Last Updated: April 8, 2016
Health Authority: United States: Food and Drug Administration
Individual Participant Data  
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 Bloodworks (Puget Sound Blood Center):
Sickle Cell Disease
Sickle Cell Anemia

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Acetylcysteine
N-monoacetylcystine
Antiviral Agents
Anti-Infective Agents
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes

ClinicalTrials.gov processed this record on July 26, 2016