The aim of this study is to investigate the influence of statin therapy on DDAVP mediated release of VWF and F VIII. We aim to investigate this by measuring F VIII and VWF levels by means of a prolonged DDAVP test prior and after 6 weeks of statin…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Bloedstollingsstoornissen
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
* vWF antigen, vWF activity and vWF propeptide plasma levels after DDAVP
stimulation, during statin therapy.
* FVIII activity and F VIII antigen plasma levels after DDAVP stimulation,
during statin therapy.
Secondary outcome
* vWF multimers, ADAMTS13 and tPA plasmalevels after DDAVP stimulation during
statin therapy.
Background summary
Currently, in Hemophilia A and Von Willebrand patients treatment with DDAVP is
the most feasible and patient friendly method of treatment. In patients with a
limited response to DDAVP or individuals with inhibitors to F VIII,
optimalisation of DDAVP treatment is all the more important. There is evidence
that statin therapy might upregulate transcription factor Kruppel-like factor 2
(KLF2) and thereby enhance WPB exocytosis. Although statin therapy has many
pleitropic effects next to its lipid lowering effects, the exact mechanism by
which statin therapy might influence the endothelium remains unclear.
Literature on this topic is scarce and conflicting. A better insight in the
influence of statin therapy on DDAVP-mediated VWF and F VIII release might open
ways to improve DDAVP treatment in these patient groups.
Study objective
The aim of this study is to investigate the influence of statin therapy on
DDAVP mediated release of VWF and F VIII. We aim to investigate this by
measuring F VIII and VWF levels by means of a prolonged DDAVP test prior and
after 6 weeks of statin therapy.
Study design
The total duration of the study is 6 weeks, in this period a DDAVP test will be
performed on two time points. The first DDAVP test will take place prior to
starting statin therapy and the second test will be performed after 6 weeks of
statin therapy. During both tests blood samples will be taken until 32 hours
after DDAVP infusion (in total 7 times per test), in each bloodsample e.g. vWF
activity and F VIII activity will be determined.
Intervention
The subjects in the study will undergo two DDAVP tests. The first DDAVP test
will take place prior to starting statin therapy and the second test will be
performed after 6 weeks of statin therapy. During both tests blood samples will
be taken until 32 hours after DDAVP infusion (in total 7 times per test). After
the first DDAVP test subjects receive 40 mg simvastatin for 6 weeks. After 6
weeks simvastatin the second DDAVP test will be performed.
Study burden and risks
There are no direct benefits for the study participants related to this study.
However, the results of the study may be relevant and beneficial to the
patients and their families as well as their treating physicians. If DDVAP
response improves after statin use, participants will be able to benefit from
optimized treatment.
Risks of study participation:
- Venipunctures: hematomas
- Statin therapy: adverse events of statin use: see studyprotocol Appendix D
- DDAVP: adverse events of DDAVP use: see study protocol Appendix E
Meibergdreef 9
1105AZ Amsterdam
NL
Meibergdreef 9
1105AZ Amsterdam
NL
Listed location countries
Age
Inclusion criteria
1. Mild hemophilia A: defined as a F VIII deficiency with a F VIII plasma concentration of 10-40 IU mL-1, confirmed on at least two occasions.
2. or Von Willebrand disease type 1: defined as a VWF deficiency with a VWF plasma concentration of 10-40 IU mL-1, confirmed on at least two occasions.
3. DDAVP response has been tested at least once before, VWF activity and VWF antigen after DDAVP should not exceed > 200 %.
4. Age: 18 * 60 years
5. Male
Exclusion criteria
1. Moderate/Severe hemophilia A: defined as a F VIII deficiency with a F VIII:C plasma concentration of * 2 IU mL-1, confirmed at at least two occasions.
2. Von Willebrand disease type 2 or 3
3. Clinical history of any other hemostatic or thrombotic disorder.
4. Clinical history of any disorder specified in Appendix C of the study protocol
5. Use of any medications specified in Appendix C of the study protocol
6. Medical indication for statin therapy.
7. Co-enrolment other clinical study
8. DDAVP response has not previously been tested or vWF antigen and vWF activity increase after previous DDAVP exposure was less than two fold.
9. First relative (brother/sister) participating in this study
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 | EUCTR2009-017060-17-NL |
| CCMO | NL30422.018.09 |