Sickle Cell DiseasePhase 1/2NACinSCDNCT01800526
A Pilot Study of N-acetylcysteine in Patients With Sickle Cell Disease
A Phase 1/2 study testing N-Acetylcysteine in people with Sickle Cell Disease and Sickle Cell Anemia, run by Bloodworks at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sickle Cell Disease, Sickle Cell Anemia
- What is being tested?
- N-Acetylcysteine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2013to 30 Jun 2020
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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
- Being tested
- N-Acetylcysteine
- Keywords
- Sickle Cell Disease, Sickle Cell Anemia
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-AcetylcysteineDrug
Oral and Intravenous administration of NAC
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: N-Acetylcysteine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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
To assess safety by evaluating subjects for adverse events during and at time points following administration.
Measured: 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
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
Measured: Before and following each NAC infusion while hospitalized
Use of pain medications in morphine equivalents
Data on morphine equivalents administered during the study hospitalization will be compared to those of past admissions.
Measured: Morphine equivalents for the hospitalization during which NAC was administered compared to past VOC 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
Measured: Days of hospitalization during study compared to past hospitalizations for VOC
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2013 (estimated)
- Study startMar 2013
- Primary completion24 Jan 2020
- Study completion30 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bloodworks
- Sponsor type
- University, hospital or other
- Collaborators
- University of Washington
- Responsible party
- Principal investigator, Barbara A. Konkle, M.D., Bloodworks
- Investigators
- Barbara A Konkle, M.D., Principal investigator, Univ. of Washington/Bloodworks Northwest
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01800526
- Sponsor's protocol ID
- 117090
- Acronym
- NACinSCD
- Status last verified
- Jul 2020
- First submitted
- 21 Jan 2013
- Last updated
- 9 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Data will be published at end of study and data made available to outside investigators after results are published by investigators
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of N-acetylcysteine in Patients With Sickle Cell Disease
- ClinicalTrials.gov ID
- NCT01800526
- Acronym / sponsor ID
- NACinSCD / 117090
- Conditions
- Sickle Cell Disease, Sickle Cell Anemia
- Keywords
- Sickle Cell Disease, Sickle Cell Anemia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- BloodworksUniversity, hospital or other
- Collaborators
- University of Washington
- Study start
- Mar 2013 (actual)
- Primary completion
- 24 Jan 2020 (actual)
- Study completion
- 30 Jun 2020 (actual)
- First posted
- 27 Feb 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Oral N-acetylcysteine (NAC) | Experimental | Drug: N-AcetylcysteineEligible 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. |
| Intravenous N-acetylcysteine (NAC) | Experimental | Drug: N-AcetylcysteineFor 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| N-AcetylcysteineOral and Intravenous administration of NAC | Drug | Intravenous N-acetylcysteine (NAC), Oral N-acetylcysteine (NAC) |
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.
5 secondary outcomes
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
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.
Pain during VOC
Time frame: Before and following each NAC infusion while hospitalized
Use of pain medications in morphine equivalents
Time frame: Morphine equivalents for the hospitalization during which NAC was administered compared to past VOC admissions
Hospital length of stay (LOS)
Time frame: Days of hospitalization during study compared to past hospitalizations for VOC
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2020.
- Individual participant dataSharing planned: Yes. Data will be published at end of study and data made available to outside investigators after results are published by investigators
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Barbara A Konkle, M.D. principal investigator
Univ. of Washington/Bloodworks Northwest
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing N-Acetylcysteine in people with Sickle Cell Disease and Sickle Cell Anemia, run by Bloodworks at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2020.