Clinical trial NCT01800526: A Pilot Study of N-acetylcysteine in Patients With Sickle Cell Disease
Official title: A Pilot Study of N-acetylcysteine in Patients With Sickle Cell Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Sickle Cell Disease
Sickle Cell Anemia
Keywords: Sickle Cell Disease
Sickle Cell Anemia
Lead sponsor: Bloodworks
Sponsor class: OTHER
Collaborators: name: University of Washington
First posted: 2013-02-27
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 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 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

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.

Primary outcomes:
measure: Laboratory measures of VWF activity
timeFrame: Part 1, Prior to during and following one day infusion or during oral administration; Part 2, daily during infusion and just following infusion completion
Secondary outcomes:
measure: Laboratory measures of red blood cell hemolysis and oxidation
timeFrame: 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
measure: Adverse events during and following NAC administration
timeFrame: Adverse events will be measured from time of consent to completion of study, with particular attention to times around and during administration.
measure: Pain during VOC
timeFrame: Before and following each NAC infusion while hospitalized
measure: Use of pain medications in morphine equivalents
timeFrame: Morphine equivalents for the hospitalization during which NAC was administered compared to past VOC admissions
measure: Hospital length of stay (LOS)
timeFrame: Days of hospitalization during study compared to past hospitalizations for VOC
Other outcomes:
Locations:
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: Univ. of Washington/Bloodworks Northwest
name: Barbara A Konkle, M.D.
role: PRINCIPAL_INVESTIGATOR
References: