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N-Acetylcysteine in Patients With Sickle Cell Disease

Information source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Sickle Cell Disease

Intervention: N-Acetylcysteine (Drug); Placebo (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Official(s) and/or principal investigator(s):
Bart Biemond, MD, PhD, Principal Investigator, Affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Karin Fijnvandraat, MD, PhD, Principal Investigator, Affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Overall contact:
Bart Biemond, MD, PhD, Phone: +31-20-5665785, Email: b.j.biemond@amc.nl

Summary

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.

Clinical Details

Official title: N-Acetylcysteine in Patients With Sickle Cell Disease - Reducing the Incidence of Daily Life Pain

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Primary outcome: The frequency of SCD related pain in daily life in days per patient

Secondary outcome:

The severity of SCD related pain in daily life, using a 0-10 numerical rating scale (NRS) in the study pain diary.

The incidence of painful crises. The rate of painful crises will be defined as the number of crises and crisis days per patient in proportion to the total time of intervention (6 months) per treatment group.

The severity of painful crises. This will be defined using a 0-10 numerical rating scale (NRS) in the pain diary.

The frequency of hospital admissions, defined as the number of admissions per patient in proportion to total time of intervention.

The length of hospital admissions, measured in days, from day of admission to day of discharge, in proportion to total time of intervention (6 months).

Time in days to first painful crisis (as defined above)

Time in days to first hospital admission for painful crisis (as defined above)

Time in days to second painful crisis (as defined above)

Time in days to second hospital admission (as defined above)

The health-related Quality of Life, as measured by use of validated questionnaires.

The SCD-related societal costs, assessed by a prospective cost-effectiveness analysis

The tolerability of NAC, defined as the number of participants with adverse events.

Frequency of use of pain medication at home. This information will be recorded by subjects in their daily pain diary, including type and dosage of pain medication.

Incidence of SCD complications.

The changes in blood markers of oxidative stress, hemolysis, hypercoagulability, inflammation, erythrocyte adhesion and endothelial dysfunction

Eligibility

Minimum age: 12 Years. Maximum age: N/A. Gender(s): Both.

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

- Use of pain medication for sickle-cell related pains on more than 15 days per month

in the past 6 months ('chronic pain').

Locations and Contacts

Bart Biemond, MD, PhD, Phone: +31-20-5665785, Email: b.j.biemond@amc.nl

CHU Brugmann, Brussels, Belgium; Recruiting
M Azerad, MD
T Besse-Hammer, MD

CHU St. Pierre, Brussels, Belgium; Recruiting
P. Hermans, MD
A. Vanderfaeillie, MD

Hôpital Erasme, Brussels, Belgium; Recruiting
F. Benghiat, MD

Hôpital Universitaire Des Enfants Reine Fabiola (HUDERF), Brussels, Belgium; Recruiting
A. Ferster, MD

UCL St. Luc, Brussels, Belgium; Recruiting
A van Damme, MD

CHR de la Citadelle, Liège, Belgium; Recruiting
M. Dresse, MD

Academic Medical Center, Amsterdam 1105 AZ, Netherlands; Recruiting
Joep Sins, MD, Phone: +31-20-5661693, Email: j.w.sins@amc.nl
Marjolein Spiering, Phone: +31-20-5665785, Email: m.spiering@amc.nl
Bart Biemond, MD, PhD, Principal Investigator
Karin Fijnvandraat, MD, PhD, Principal Investigator
Joep Sins, MD, Sub-Investigator
Harriët Heijboer, MD, PhD, Sub-Investigator

University Medical Center Groningen, Groningen 9713 GZ, Netherlands; Completed

Erasmus Medical Center, Rotterdam 3015 AA, Netherlands; Completed

Haga Hospital, The Hague 2545 CH, Netherlands; Completed

Guys' & St. Thomas Hospital, London, United Kingdom; Recruiting
R. Kesse-Adu, MD

Additional Information

Related publications:

Smith WR, Penberthy LT, Bovbjerg VE, McClish DK, Roberts JD, Dahman B, Aisiku IP, Levenson JL, Roseff SD. Daily assessment of pain in adults with sickle cell disease. Ann Intern Med. 2008 Jan 15;148(2):94-101.

Nur E, Brandjes DP, Schnog JJ, Otten HM, Fijnvandraat K, Schalkwijk CG, Biemond BJ; CURAMA Study Group. Plasma levels of advanced glycation end products are associated with haemolysis-related organ complications in sickle cell patients. Br J Haematol. 2010 Oct;151(1):62-9. doi: 10.1111/j.1365-2141.2010.08320.x. Epub 2010 Jul 30.

Nur E, Biemond BJ, Otten HM, Brandjes DP, Schnog JJ; CURAMA Study Group. Oxidative stress in sickle cell disease; pathophysiology and potential implications for disease management. Am J Hematol. 2011 Jun;86(6):484-9. doi: 10.1002/ajh.22012. Epub 2011 May 4. Review.

Nur E, Verwijs M, de Waart DR, Schnog JJ, Otten HM, Brandjes DP, Biemond BJ, Elferink RP; CURAMA Study Group. Increased efflux of oxidized glutathione (GSSG) causes glutathione depletion and potentially diminishes antioxidant defense in sickle erythrocytes. Biochim Biophys Acta. 2011 Nov;1812(11):1412-7. doi: 10.1016/j.bbadis.2011.04.011. Epub 2011 May 3.

Nur E, Brandjes DP, Teerlink T, Otten HM, Oude Elferink RP, Muskiet F, Evers LM, ten Cate H, Biemond BJ, Duits AJ, Schnog JJ; CURAMA study group. N-acetylcysteine reduces oxidative stress in sickle cell patients. Ann Hematol. 2012 Jul;91(7):1097-105. doi: 10.1007/s00277-011-1404-z. Epub 2012 Feb 10.

Pace BS, Shartava A, Pack-Mabien A, Mulekar M, Ardia A, Goodman SR. Effects of N-acetylcysteine on dense cell formation in sickle cell disease. Am J Hematol. 2003 May;73(1):26-32.

Somjee SS, Warrier RP, Thomson JL, Ory-Ascani J, Hempe JM. Advanced glycation end-products in sickle cell anaemia. Br J Haematol. 2005 Jan;128(1):112-8.

van Tuijn CF, van Beers EJ, Schnog JJ, Biemond BJ. Pain rate and social circumstances rather than cumulative organ damage determine the quality of life in adults with sickle cell disease. Am J Hematol. 2010 Jul;85(7):532-5. doi: 10.1002/ajh.21731.

Starting date: April 2013
Last updated: August 12, 2015

Page last updated: August 23, 2015

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