Clinical Trial: A Pilot Study of N-acetylcysteine in Patients With Sickle Cell Disease

Study Status: Enrolling by invitation
Recruit Status: Enrolling by invitation
Study Type: Interventional

Official Title: A Pilot Study of N-acetylcysteine in Patients With Sickle Cell Disease

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.


Detailed Summary:

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.


Sponsor: Bloodworks (Puget Sound Blood Center)

Current Primary Outcome: 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.


Original Primary Outcome: 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. ]

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.


Current Secondary Outcome:

  • 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.
  • 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.
  • 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
  • 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.
  • 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


Original Secondary Outcome:

  • 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. ]
    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. ]
    To assess safety by evaluating subjects for adverse events including vaso-occlusive crises and bleeding symptoms during and at time points following administration.


Information By: Bloodworks (Puget Sound Blood Center)

Dates:
Date Received: January 21, 2013
Date Started: March 2013
Date Completion: August 2018
Last Updated: May 15, 2017
Last Verified: May 2017