Reducing the incidence of daily life pain in patients with sickle cell disease

Pain is an invalidating hallmark of Sickle Cell Disease (SCD) and has a
considerable impact on the Quality of Life (QoL) of patients and the medical
health care system. Oxidative stress is hypothesized to play a central role in
its pathophysiology. This is supported by the fact that markers of oxidative
stress are associated with the extent of chronic organ damage and pain. In an
open label randomized pilot study we demonstrated that administration of a
scavenger of free oxygen radicals (oral N-Acetylcysteine; NAC) during 6 weeks
reduced markers of oxidative stress. In another pilot study a profound effect
of NAC on the hospitalization rate for painful crises was demonstrated. Our
hypothesis is that NAC is able to reduce the incidence of daily life pain in
patients with SCD

In this study the effect of the administration of NAC on the frequency and
severity of pain and painful crises in daily life will be assessed as well as
the related frequency and length of hospital admissions and health related
quality of life. In addition, several biomarkers will be monitored and societal
costs will be evaluated.

SCD patients are treated with either NAC or placebo in a multicenter,
randomized, controlled double blind trial for a period of 6 months. A run-in
period of 2 weeks will be take place before randomization to evaluate
compliance concerning the completion of a pain diary. Patients with
insufficient compliance will not be randomised for further study participation.
Total duration of this trial including follow-up will be 6.5 months. Patients
are treated with either twice daily 1 tablet of 600mg NAC orally or 1 tablet
placebo twice daily.

N-acetylcystein 600mg twice a day or placebo twice a day

The risks of participation in this study are predicted to be negligible. NAC is
a drug that has been registered for years for other indications and has been
studied in a wide age range, in large patient cohorts with different dosages.
It has proven to be safe and have only infrequent, limited side effects
(occasionally nausea, vomiting or urticaria).
Patients will have to take study medication twice daily. Furthermore,
participants will undergo blood sampling more frequently than normally; Every 3
months, in total 3 times, instead of 1-2 times with regular follow-up. They
will be seen monthly in outpatient department to monitor outcomes instead of
once every 6 months. Also, subjects will have to fill out a daily pain diary
for a total of 6.5 months and will be asked to fill out three questionnaires at
0, 3 and 6 months after the start of intervention.

Potential benefit of this study is that NAC may be able to reduce the frequency
and/or severity of pain and painful crises and related hospital admission by
reducing oxidative stress. If we are able to find evidence for our hypothesis,
the use of NAC in SCD patients may lead to fewer pain complaints, with a
potential improvement in QoL, and a potential decrease in pain related
healthcare consumption and its costs worldwide.