Heterozigous Familial Hypercholesterolemia Clinical Trial
Official title:
Evaluation of Chylomicrons Metabolism in Sub-Clinical Atherosclerosis in Patients Whit Heterozigous Familial Hypercholesterolemia (FH) Treated With Statin Plus Ezetimibe
| NCT number | NCT00475826 |
| Other study ID # | 1067/06 |
| Secondary ID | |
| Status | Recruiting |
| Phase | N/A |
| First received | May 18, 2007 |
| Last updated | March 20, 2008 |
| Start date | April 2007 |
Study Title: Evaluation of chylomicrons metabolism in sub-clinical atherosclerosis in
patients whit Heterozigous Familial Hypercholesterolemia (FH) treated with statin plus
ezetimibe.
Background:
Coronary artery calcification (CAC) is a marker of sub-clinical coronary atherosclerosis
which correlates with higher risk of clinical events. It was already demonstrated that CAC
is more prevalent in patients with FH compared with normal individuals. A number of studies
demonstrated that plasmatic removal of chylomicrons is defective in patients with
atherosclerosis. Despite the fact that is still controversial whether this impairment occurs
in patients with HF when compared to normal controls, the kinetics of chylomicrons has not
been studied in HF patients with and without atherosclerosis and more important, it is not
clear if those changes may be observed in the sub-clinical disease, as reported for CAC in
asymptomatic individuals.
Previous studies have demonstrated the inverse correlation among LDL-C levels and the
removal of remnants chylomicrons using artificial chylomicrons technique. It is also well
known that high doses of more potent statins are more effective to remove chylomicrons from
the plasma due to better expression of LDL-C receptors through plasma LDL-C reduction. It
was not evaluated yet if the association of ezetimibe and statin, enhancing LDL-C receptors
expression in the liver would enhance the efficacy of the monotherapy with statins to remove
artificial chylomicrons in patients with HF.
Study design:
Open, randomized, single-blinded study in which twenty six outpatients from the Lipids
Clinical Unit at the Heart Institute (INCOR), University of São Paulo, previously diagnosed
with FH according to US MED PED criteria, without history of CD and a CAC evaluation by MSCT
(Multiple Sensors Computed Tomography) in the previous year will be compared to 26 control
individuals matched by age and sex collected from the database of the Lipids Metabolism
Laboratory.
Patients will be randomized to receive simvastatin 40 mg as monotherapy or in combination
with ezetimibe 10 mg and will undergoing three kinetics studies to demonstrate the effects
of simvastatin 40 mg on the kinetics of the chylomicrons along with other laboratorial
dosages ( lipid fractions, hepatic enzymes and CK).
The primary endpoint of this study is to evaluate if there is any correlation among the
reduction of the plasma clearance of chylomicrons by the artificial chylomicrons technique
and the presence of sub-clinical atherosclerosis; the secondary endpoint is to evaluate if
ezetimibe/simvastatin enhances the effects of simvastatin alone in the removal of
chylomicrons in patients with HF.
| Status | Recruiting |
| Enrollment | 0 |
| Est. completion date | |
| Est. primary completion date | |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years to 70 Years |
| Eligibility |
Inclusion Criteria: - Heterozigous Familial Hypercholesterolemia patients - Age 18 to 70 - Male and Female - Coronary artery calcification Exclusion Criteria: - Coronary artery disease - Cerebrovascular disease - Diabetes Mellitus - Heart Failure Class III-IV - Thyroid disease - Peripheral Artery disease - Pregnancy, women without anticonceptive method - Kidney disease or calcium disturbs - Thoracic Cancer - Use of Beta Blockers, diuretics, glucocorticoids ,hormone replacement therapy except oral anticonception - Use of lipid lowering drugs for the last six weeks |
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Single Blind
| Country | Name | City | State |
|---|---|---|---|
| Brazil | Heart Institute | Sao Paulo | SP |
| Lead Sponsor | Collaborator |
|---|---|
| University of Sao Paulo | Merck Sharp & Dohme Corp. |
Brazil,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Evaluate if there is any correlation among the reduction of the plasma clearance of chylomicrons by the artificial chylomicrons technique and the presence of sub-clinical atherosclerosis | Five months | ||
| Secondary | Evaluate if ezetimibe/simvastatin enhances the effects of simvastatin alone in the removal of chylomicrons in patients with HF. | Five Months |