Expression of Pro- and Anti-inflammatory Cytokines During Anti-PCSK9 in Familial Hypercholesterolemia

NCT06231459 | Completed Phase 4 DMC

• 1 other identifier: 061.2019
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hypercholesterolemia, Familial

Outcome Measures

Primary Outcomes (1)

• lower of serum lipids

  lower serum LDL below 100mg/dL

  1 month

Secondary Outcomes (1)

• modification of pro-inflammatory mediators

  1 month

Study Arms (1)

Evolocumab

EXPERIMENTAL

Evolocumab 140 mg was administered intramuscularly every two weeks at the discretion of their physiciansm according to LDLc response.

Drug: Evolocumab

Interventions

Evolocumab DRUG

Evolocumab 140 mg was administered intramuscularly every two weeks at the discretion of their physiciansm according to LDLc response. 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).

Also known as: repatha

Evolocumab

Eligibility Criteria

• Age: 18 Years - 80 Years
• Gender Eligibility Details: Asked self-representation of gender identity.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• We excluded patients with infections, neoplasia or under oncological therapy.

Sponsors & Collaborators

• Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado: lead

Study Sites (1)

National Medical Center "20 de Noviembre", ISSSTE

Mexico City, 03100, Mexico

Location

Related Publications (1)

• 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.

  PMID: 36632236 BACKGROUND

MeSH Terms

Conditions

Hyperlipoproteinemia Type II

Interventions

evolocumab

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Julieta D Morales-Portano, MD

  Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Model Details: Non-randomized, non-controlled, before-after comparison, quasiexperimental, single-center study.

Study Record Dates

• First Submitted: January 22, 2024
• First Posted: January 30, 2024
• Study Start: January 1, 2019
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2020
• Last Updated: January 30, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)