N-Acetylcysteine in Patients With Sickle Cell Disease (NAC)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor:
Collaborators:
Erasmus Medical Center
Haga Hospital
University Medical Centre Groningen
ZonMw: The Netherlands Organisation for Health Research and Development
Information provided by (Responsible Party):
B.J. Biemond, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier:
NCT01849016
First received: May 6, 2013
Last updated: October 7, 2013
Last verified: October 2013
  Purpose

The primary aim of this study is to evaluate the effect of the drug N-Acetylcysteine on the frequency of pain in daily life in patients with Sickle Cell Disease (SCD).

Pain is an invalidating hallmark of this disease and has a considerable impact on the Quality of Life of patients and the medical health care system. Oxidative stress is hypothesized to play a central role in its pathophysiology. In pilot studies the administration of N-Acetylcysteine (NAC) resulted in a reduction of oxidative stress. Moreover, administration of NAC seemed to decrease hospitalization for painful crises in a small pilot study in patients with SCD.

This study will be performed as a multicenter, randomized, controlled trial where patients will be treated with either NAC or placebo for a period of 6 months. The investigators expect that NAC can reduce the frequency of pain in patients with SCD, thereby improving their quality of life and participation in society.


Condition Intervention Phase
Sickle Cell Disease
Drug: N-Acetylcysteine
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: N-Acetylcysteine in Patients With Sickle Cell Disease - Reducing the Incidence of Daily Life Pain

Resource links provided by NLM:


Further study details as provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):

Primary Outcome Measures:
  • The frequency of SCD related pain in daily life in patients with Sickle Cell Disease [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The severity of SCD related pain in daily life [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • The incidence and severity of painful crises [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • The frequency and length of hospital admissions [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • The health-related Quality of Life [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • The SCD-related societal costs [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • The tolerability of NAC [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Frequency of use of pain medication at home [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Frequency of SCD complications (e.g. acute chest syndrome) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • The changes in hematological markers of oxidative stress, hemolysis, hypercoagulability, inflammation, erythrocyte adhesion and endothelial dysfunction [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 140
Study Start Date: April 2013
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: N-Acetylcysteine
N-Acetylcysteine 600mg 1 oral tablet twice daily during 6 months
Drug: N-Acetylcysteine
Other Names:
  • Acetylcysteine
  • Fluimicil
  • Acetadote
Placebo Comparator: Placebo
Placebo 1 oral tablet twice daily during 6 months
Drug: Placebo

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 12 years or older
  • Sickle cell disease, either homozygous sickle cell disease (HbSS), compound heterozygous sickle cell disease (HbSC), HbSβ0 or HbSβ+ thalassemia
  • History of at least 1.0 painful crisis per year in the past 3 years (visit to medical facility is not required)

Exclusion Criteria:

  • Chronic blood transfusion or transfusion in the preceding 3 months
  • Painful crisis in the last 4 weeks (with respect to the moment of inclusion)
  • Pregnancy, breast feeding or the desire to get pregnant in the following 7 months
  • Known active gastric/duodenal ulcers
  • Hydroxycarbamide (HC) treatment with unstable dose in the last 3 months or started on HC shorter then 6 months prior to study
  • Known poor compliance in earlier trials regarding the completion of pain diaries
  • Insufficient compliance in run-in period
  • Known hypersensitivity to acetylcysteine or one of the other components of the study medication
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01849016

Contacts
Contact: Bart Biemond, MD, PhD +31-20-5665785 b.j.biemond@amc.nl
Contact: Karin Fijnvandraat, MD, PhD +31-20-5662727 c.j.fijnvandraat@amc.nl

Locations
Netherlands
Academic Medical Center Recruiting
Amsterdam, Netherlands, 1105 AZ
Contact: Joep Sins, MD    +31-20-5661693    j.w.sins@amc.nl   
Contact: Marjolein Spiering    +31-20-5665785    m.spiering@amc.nl   
Principal Investigator: Bart Biemond, MD, PhD         
Principal Investigator: Karin Fijnvandraat, MD, PhD         
Sub-Investigator: Joep Sins, MD         
Sub-Investigator: Harriët Heijboer, MD, PhD         
University Medical Center Groningen Recruiting
Groningen, Netherlands, 9713 GZ
Principal Investigator: Marco de Groot, MD, PhD         
Erasmus Medical Center Recruiting
Rotterdam, Netherlands, 3015 AA
Principal Investigator: Anita Rijneveld, MD, PhD         
Principal Investigator: Marjon Cnossen, MD, PhD         
Haga Hospital Recruiting
The Hague, Netherlands, 2545 CH
Principal Investigator: Jean-Louis Kerkhoffs, MD, PhD         
Principal Investigator: Alfred van Meurs, MD, PhD         
Sponsors and Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Erasmus Medical Center
Haga Hospital
University Medical Centre Groningen
ZonMw: The Netherlands Organisation for Health Research and Development
Investigators
Principal Investigator: Bart Biemond, MD, PhD Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Principal Investigator: Karin Fijnvandraat, MD, PhD Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
  More Information

Publications:

Responsible Party: B.J. Biemond, dr., Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT01849016     History of Changes
Other Study ID Numbers: NAC trial, 2012-004892-37, 171201003, NL 41205.018.12
Study First Received: May 6, 2013
Last Updated: October 7, 2013
Health Authority: Netherlands: Dutch Health Care Inspectorate
Netherlands: Medical Ethics Review Committee (METC)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
Sickle Cell Disease
Sickle Cell Anemia
Pain
N-Acetylcysteine
Acetylcysteine
Oxidative stress

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Acetylcysteine
N-monoacetylcystine
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes

ClinicalTrials.gov processed this record on July 31, 2014