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

NCT01800526 | Completed Phase 1 DMC

• 1 other identifier: 117090
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

Sickle Cell Disease; Sickle Cell Anemia

Keywords

Sickle Cell Disease; Sickle Cell Anemia

Outcome Measures

Primary Outcomes (1)

• Laboratory measures of VWF activity

  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.

  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 (5)

• Laboratory measures of red blood cell hemolysis and oxidation

  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

• Adverse events during and following NAC administration

  Adverse events will be measured from time of consent to completion of study, with particular attention to times around and during administration.

• Pain during VOC

  Before and following each NAC infusion while hospitalized

• Use of pain medications in morphine equivalents

  Morphine equivalents for the hospitalization during which NAC was administered compared to past VOC admissions

• Hospital length of stay (LOS)

  Days of hospitalization during study compared to past hospitalizations for VOC

Study Arms (2)

Oral N-acetylcysteine (NAC)

EXPERIMENTAL

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

Intravenous N-acetylcysteine (NAC)

EXPERIMENTAL

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

Interventions

N-Acetylcysteine DRUG

Oral and Intravenous administration of NAC

Intravenous N-acetylcysteine (NAC); Oral N-acetylcysteine (NAC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>= 18 years of age
• 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.
• For females of reproductive age, use of contraception and negative pregnancy test

You may not qualify if:

• An additional hematologic diagnosis
• Hemoglobin (Hgb) \< 7gm/dL for part 1, \< 6 gm/dL for part 2.
• Asthma requiring medication
• Liver function tests \[alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (BilliT) \> three times upper normal limit for Part 1.
• Chronic transfusion therapy, or transfusion within 2 months of enrollment. For part 2 anticipated need for simple or exchange transfusion during hospitalization.
• 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.
• Pregnancy or nursing
• Receiving another investigational drug
• Known allergy to NAC
• Per subject's physician not medically stable enough to participate
• Taking nitroglycerin, carbamazepine, or phosphodiesterase 5 (PDE5) inhibitors
• Abnormal baseline coagulation tests (\> 1.5 times normal limits)
• Platelets \<150,000/microliter for Part 1.
• For part 2, already enrolled in study twice.

Sponsors & Collaborators

• Bloodworks: lead
• University of Washington: collaborator

Study Sites (1)

University of Washington

Seattle, Washington, 98106, United States

Location

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Barbara A Konkle, M.D.

  Univ. of Washington/Bloodworks Northwest

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Clinical and Translational Research

Study Record Dates

• First Submitted: January 21, 2013
• First Posted: February 27, 2013
• Study Start: March 1, 2013
• Primary Completion: January 24, 2020
• Study Completion: June 30, 2020
• Last Updated: July 9, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will share

Locations

US (1)