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

NCT ID: NCT01800526

Last Updated: 2020-07-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-31
• Study Completion Date: 2020-06-30

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.

Conditions

Sickle Cell Disease; Sickle Cell Anemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

N-Acetylcysteine

Intervention Type: DRUG

Oral and Intravenous administration of NAC

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.

Group Type: EXPERIMENTAL

N-Acetylcysteine

Intervention Type: DRUG

Oral and Intravenous administration of NAC

Interventions

N-Acetylcysteine

Oral and Intravenous administration of NAC

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Washington

OTHER

Sponsor Role: collaborator

Bloodworks

OTHER

Sponsor Role: lead

Responsible Party

Barbara A. Konkle, M.D.

Director, Clinical and Translational Research

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Barbara A Konkle, M.D.

Role: PRINCIPAL_INVESTIGATOR

Univ. of Washington/Bloodworks Northwest

Locations

University of Washington

Seattle, Washington, United States

Countries

United States

Other Identifiers

117090

Identifier Type: -

Identifier Source: org_study_id