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

Primary Purpose

Sickle Cell Disease, Sickle Cell Anemia

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

N-Acetylcysteine

About this trial

This is an interventional treatment trial for Sickle Cell Disease focused on measuring Sickle Cell Disease, Sickle Cell Anemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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.

Sites / Locations

University of Washington

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Oral N-acetylcysteine (NAC)

Intravenous N-acetylcysteine (NAC)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Laboratory measures of red blood cell hemolysis and oxidation

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

To assess safety by evaluating subjects for adverse events during and at time points following administration.

Pain during VOC

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

Data on morphine equivalents administered during the study hospitalization will be compared to those of past admissions.

Hospital length of stay (LOS)

LOS will be calculated by days of hospitalization when study drug is administered compared to past LOS for VOC admissions

Full Information

NCT ID

NCT01800526

First Posted

January 21, 2013

Last Updated

July 7, 2020

Sponsor

Bloodworks

Collaborators

University of Washington

1. Study Identification

Unique Protocol Identification Number

NCT01800526

Brief Title

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

Acronym

NACinSCD

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2020

Overall Recruitment Status

Completed

Study Start Date

March 2013 (Actual)

Primary Completion Date

January 24, 2020 (Actual)

Study Completion Date

June 30, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Bloodworks

Collaborators

University of Washington

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Sickle Cell Disease, Sickle Cell Anemia

Keywords

Sickle Cell Disease, Sickle Cell Anemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

21 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Oral N-acetylcysteine (NAC)

Arm Type

Experimental

Arm Description

Arm Title

Intravenous N-acetylcysteine (NAC)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

N-Acetylcysteine

Intervention Description

Oral and Intravenous administration of NAC

Primary Outcome Measure Information:

Title

Laboratory measures of VWF activity

Description

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.

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

Secondary Outcome Measure Information:

Title

Laboratory measures of red blood cell hemolysis and oxidation

Description

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

Title

Adverse events during and following NAC administration

Description

To assess safety by evaluating subjects for adverse events during and at time points following 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.

Title

Pain during VOC

Description

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

Time Frame

Before and following each NAC infusion while hospitalized

Title

Use of pain medications in morphine equivalents

Description

Data on morphine equivalents administered during the study hospitalization will be compared to those of past admissions.

Time Frame

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

Title

Hospital length of stay (LOS)

Description

LOS will be calculated by days of hospitalization when study drug is administered compared to past LOS for VOC admissions

Time Frame

Days of hospitalization during study compared to past hospitalizations for VOC

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Barbara A Konkle, M.D.

Organizational Affiliation

Univ. of Washington/Bloodworks Northwest

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Washington

City

Seattle

State/Province

Washington

ZIP/Postal Code

98106

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Data will be published at end of study and data made available to outside investigators after results are published by investigators

Learn more about this trial

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

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