STUDY OBJECTIVESTo determine whether NAC therapy results in decreased red cell PS exposure, endothelial activation, inflammation, and reduction clotting activation in the steady state.
ID
Source
Brief title
Condition
- Haemoglobinopathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary outcome measures are the effects of NAC on the laboratory markers
described below.
* hemoglobin levels, red blood cell counts, reticulocyte counts, leukocyte
counts and differentiation, platelet counts, erythrocyte sedimentation rate
will be determined with a automated cell counter.
* A blood smear will be analyzed microscopically for the number of ISC per
field, as well as the number of Heinz bodies
* Intra-erythrocytic GSH and GSSG levels
* NO availability (ratios of aminoacids involved in arginine metabolism)
* SRBC PS exposure will be determined with flow cytometric quantification
* Inflammation and endothelial activation (Serum levels of high sensitive CRP,
sVCAM-1, ET-1, and IL-8)
* Coagulation activation (pro-thrombin fragments (F1.2), D-dimer levels,
protein S (free and total) and C activity, vWF-Ag activity)
Secondary outcome
Secondary outcome measures are tolerability of study medication at every visit
by history taking and by scoring of a NAC for SCD check-list.
Background summary
We hypothesize that treatment of sickle cell patients with N-Acetylcystein
(NAC)results in reduced red cell phosphatidylserine exposure, reduced
endothelial activation, increased NO availability, reduced coagulation
activation and reduced inflammation detectable with specific laboratory
testing, as well as a reduction of ISC's and Heinz Body formation.
Study objective
STUDY OBJECTIVES
To determine whether NAC therapy results in decreased red cell PS exposure,
endothelial activation, inflammation, and reduction clotting activation in the
steady state.
Study design
Consecutive patients at the outclinic of Academic Medical Centre will be
screened for study elegibility. Adult patients with SCD will receive daily NAC
in a total dose of 2400mg (N=5) or 1200mg (N=5). Venous blood samples will be
drawn for determination of laboratory endpoints. For estimation of base-line
parameters, samples will be drawn at two weekly intervals for 3 times (T0, 1
and 2). Therapy is then initiated immediately after drawing blood for T2 with
1200mg or 600mg NAC twice daily (8:00 and 20:00) for 6 weeks (blood will be
drawn at week 6, 8 and 10 of the study period; T3, 4 and 5), where after
therapy is stopped. After cessation blood will be drawn again at week 12, week
14 and week 16 (T6, T7 and T8). The dosage employed has been previously safely
used, also in patients with SCD, and a reduction of the percentage of dense
cells is observed in vivo at this dosage (see Appendix A).
Intervention
Adult patients with SCD will receive daily NAC in a total dose of 2400mg (N=5)
or 1200mg (N=5) for six weeks.
Study burden and risks
The most important burden for the patient are the nine visits to our hospital
as well as the nine venipunctures during 16 weeks. Possible side-effects of the
NAC treatment are an additional burden and risk for the patient.
Gastrointestinal complaints are possible. Hypersensitivity is rarely seen as a
side effect of NAC
Meibergdreef 9
1100 DD Amsterdam
Nederland
Meibergdreef 9
1100 DD Amsterdam
Nederland
Listed location countries
Age
Inclusion criteria
1. High performance liquid chromatography confirmed diagnosis of HbSS, HbSC or HbSb genotype
2. Aged 18-65 years
3. Written informed consent
Exclusion criteria
1. Bloodtransfusion in the preceding four months
2. Pregnancy or the desire to get pregnant in the following 7 months
3. Concommitant use of hydroxyurea, oral anticontraceptives or other estrogen containing preparations, vitamin K antagonists or other oral anticoagulants, or contraindications for NAC.
4. Impaired renal function of more than 60% (as assessed by the Kockroft-Gauld equation)
5. Known gatsric or duodenal ulcer
6. Concomittant use of anti-hypertensives, sildefanil or nitrates.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2006-005889-40-NL |
| CCMO | NL15108.018.06 |