Hypercholesterolemia, Familial Clinical Trial
— CytoEx-PCSK9Official title:
Expression of Pro- and Anti-inflammatory Cytokines During Anti-PCSK9 Therapy in Patients With Statin-resistant Familial Hypercholesterolemia
Statins have been shown to reduce LDL cholesterol (LCLc) levels, stabilizing atheromatous plaque, reversing endothelial dysfunction and decreasing thrombogenesis. Novel pharmacological approaches, such as PCSK9 inhibitors (PCSK9i), effectively reduce LDL-c. In the clinical setting, there are cases of dyslipidemia showing lack of response to statin, known as statin-resistant familial hypercholesterolemia (SR-FH), where patients maintain a high cardiovascular risk despite statin therapy. Then, therapeutic alternatives are required. PCSK9i has shown to reduce cholesterol levels and risk of cardiovascular disease, particularly in patients with statin-resistant familial hypercholesterolemia; and recently, it has been hypothesized that PCSK9i have an effect on inflammation. Aim. To evaluate the effect of anti-PCSK9 treatment on markers related to the inflammatory response in patients with SR-FH. Methods. Non-randomized, non-controlled, before-after comparison, quasiexperimental, single-center study on patients older than 18 years, with diagnosis statin-resistant FH (SR-FH), who were attended at the Cardiology Department, Centro Médico Nacional "20 de Noviembre ISSSTE", Mexico City. SR-FH was defined as symptomatic cardiovascular disease accompanied by LDL-C concentration higher than 160 mg/dL despite maximally tolerated statin dose. Clinical-demographic and anthropometry data were collected during a direct interview. Blood sample was processed to obtain glycated hemoglobin complete blood count and serum lipids. Likewise, flow cytometry was used to characterize baseline circulating M1-, M2-macrophages and monocytes. Multiplexing of plasma samples was used to compare plasma fraktaline, IL-1, IL-4, IL-6, IL-8, IL-10, MCP-1 and TNF-alpha. Endpoints consisted of: 1) lower serum lipids; 2) modification of pro-inflammatory mediators (neutrophils, lymphocytes, NtLR, soluble pro-inflammatory cytokines). Quatitative data were resumed as mean ± SD; while categorical data as n(%).One-way T-test was applied. Statistical significance was considered if p <0.05.
Status | Completed |
Enrollment | 20 |
Est. completion date | December 31, 2020 |
Est. primary completion date | December 31, 2020 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 80 Years |
Eligibility | Inclusion Criteria: - Patients older than 18 years, with diagnosis statin-resistant FH (SR-FH), who were attended at the Cardiology Department, Centro Médico Nacional "20 de Noviembre ISSSTE", Mexico City. SR-FH was defined as symptomatic cardiovascular disease accompanied by LDL-C concentration higher than 160 mg/dL despite maximally tolerated statin dose Exclusion Criteria: - We excluded patients with infections, neoplasia or under oncological therapy. |
Country | Name | City | State |
---|---|---|---|
Mexico | National Medical Center "20 de Noviembre", ISSSTE | Mexico City |
Lead Sponsor | Collaborator |
---|---|
Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado |
Mexico,
D'Onofrio N, Prattichizzo F, Marfella R, Sardu C, Martino E, Scisciola L, Marfella L, Grotta R, Frige C, Paolisso G, Ceriello A, Balestrieri ML. SIRT3 mediates the effects of PCSK9 inhibitors on inflammation, autophagy, and oxidative stress in endothelial cells. Theranostics. 2023 Jan 1;13(2):531-542. doi: 10.7150/thno.80289. eCollection 2023. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | lower of serum lipids | lower serum LDL below 100mg/dL | 1 month | |
Secondary | modification of pro-inflammatory mediators | modification of pro-inflammatory mediators, like neutrophils, lymphocytes, NtLR, soluble pro-inflammatory cytokines. | 1 month |
Status | Clinical Trial | Phase | |
---|---|---|---|
Terminated |
NCT00384293 -
Carotid IMT (Intima Media Thickening) Study (0524A-041)(TERMINATED)
|
Phase 3 | |
Completed |
NCT04722068 -
Regeneron 1331 Kinetics Sub-Study HoFH
|
N/A | |
Completed |
NCT04118348 -
Evaluating the Efficacy of Pediatric Lipid Screening Alerts
|
N/A | |
Completed |
NCT00000594 -
NHLBI Type II Coronary Intervention Study
|
Phase 3 | |
Completed |
NCT04526457 -
Is Family Screening Improved by Genetic Testing of Familial Hypercholesterolemia
|
N/A | |
Completed |
NCT01753232 -
Safety and Efficacy of the DALI LDL-adsorber and MONET Lipoprotein Filter
|
N/A | |
Completed |
NCT03018678 -
Screening Protocol for a Gene Therapy Trial in Subjects With Homozygous Familial Hypercholesterolemia
|
||
Completed |
NCT00134485 -
Study To Evaluate The Safety And Efficacy Of Torcetrapib/Atorvastatin In Subjects With Familial Hypercholerolemia
|
Phase 3 | |
Completed |
NCT00134511 -
Study To Evaluate The Effect Of Torcetrapib/Atorvastatin In Patients With Genetic High Cholesterol Disorder
|
Phase 3 | |
Recruiting |
NCT04073797 -
PET Imaging of Inflammation and Lipid Lowering Study
|
N/A | |
Terminated |
NCT01583647 -
A Study of Extended-release (ER) Niacin/Laropiprant in Adolescents With Heterozygous Familial Hypercholesterolemia (MK-0524A-158)
|
Phase 1 | |
Completed |
NCT00515307 -
Bone Marrow Stem Cells as a Source of Allogenic Hepatocyte Transplantation in Homozygous Familial Hypercholesterolemia
|
Phase 1 | |
Recruiting |
NCT04656028 -
Genetic Testing and Motivational Counseling for FH
|
N/A | |
Terminated |
NCT00092833 -
Investigational Drug in Patients With Hypercholesterolemia or in Patients With Sitosterolemia (0653-026)(COMPLETED)
|
Phase 3 | |
Active, not recruiting |
NCT04837638 -
Diet Quality and Coronary Artery Calcification in Adults With Heterozygous Familial Hypercholesterolemia
|
||
Completed |
NCT00280995 -
Dose-escalating Safety Study of ISIS 301012 in Homozygous Familial Hypercholesterolemia Subjects on Lipid Lowering Therapy
|
Phase 2 | |
Completed |
NCT01524289 -
Study to Assess the Tolerability and Efficacy of Anacetrapib (MK-0859) Co-Administered With Statin in Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-020)
|
Phase 3 | |
Completed |
NCT00281008 -
Study of ISIS 301012 (Mipomersen) in Heterozygous Familial Hypercholesterolemia Subjects on Lipid Lowering Therapy
|
Phase 2 | |
Recruiting |
NCT03989167 -
Clinical Decision Support for Familial Hypercholesterolemia
|
N/A | |
Completed |
NCT03795038 -
Comparison of the Plasma Lipoprotein Apheresis Systems DIAMED and MONET vs. the Whole Blood Apheresis System DALI
|
N/A |