Molecular Mechanisms and Carotid Atherosclerosis

NCT03962686 | Completed

• 1 other identifier: SecondUNI 22.05.2019
• Study Type: observational
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

The role of methylase system and Proprotein convertase subtilisin/kexin type 9 (PCSK9) in the accelerated atherosclerotic progression of diabetic patients is unclear. Authors will evaluate methylase activity and PCSK9 in carotid plaques of asymptomatic diabetic and non diabetic patients, as well as the effect of statin added to PCSK9 inhibitors (PCSK9i) therapy vs. statin alone in diabetic plaques. Plaques will be obtained from 43 type 2 diabetic and 30 non diabetic patients undergoing carotid endarterectomy. Diabetic patients will receive statin therapy (n 23) or statin plus PCSK9i (140 mg of evolocumab; n 20) or placebo (n 23) for 4 months before scheduled endarterectomy. Plaques will be analyzed for macrophages (CD68), T-cells (CD3), inflammatory cells (HLADR), methylase activity, nuclear factor (NF)-KB, tumor necrosis factor (TNF)-alpha, nitrotyrosine, matrix metalloproteinase (MMP) and collagen content (immunohistochemistry and enzyme- linked immunosorbent assay. Authors' study hypothesis is that methylase and PCSK9 over-activity will be associated with enhanced inflammatory reaction and NF-KB expression in diabetic plaques. Secondly, the inhibition of methylase activity in atherosclerotic lesions of diabetic patients by metformin plus SLGT2i might be associated with morphological and compositional characteristics of a potential stable plaque phenotype, possibly by down regulating NF-KB-mediated inflammatory pathways.

Conditions

Diabetes Mellitus, Type 2; Atherosclerosis of Artery; Atherosclerotic Plaque

Outcome Measures

Primary Outcomes (1)

• methylase status

  to evaluate the activity (over vs. hypo activation) of methylase complex in atherosclerotic carotid plaques of normoglycemics vs. DM patients, and of DM patients treated with statin vs. DM patients previous treated by statin plus PCSK9i

  12 months

Study Arms (3)

normoglycemics

In this cohort will be enrolled 30 normoglycemics patients affected by carotid artery atherosclerotic and evidence of atherosclerotic plaque causing an endolumninal stenosis \> 60%. These patients will receive a surgical intervention to remove the atherosclerotic plaque and to revascularize the obstructed coronary artery vessel.

patients with diabetes mellitus (DM) treated with statin

In this cohort will be enrolled 23 DM patients affected by carotid artery atherosclerotic and evidence of atherosclerotic plaque causing an endolumninal stenosis \> 60%. These patients will receive a surgical intervention to remove the atherosclerotic plaque and to revascularize the obstructed coronary artery vessel.

patients with diabetes mellitus (DM) treated with statin plus PCSK9i

In this cohort will be enrolled 20 DM patients affected by carotid artery atherosclerotic and evidence of atherosclerotic plaque causing an endolumninal stenosis \> 60%. These patients will receive a surgical intervention to remove the atherosclerotic plaque and to revascularize the obstructed coronary artery vessel. These patients were treated before the surgical intervention by statin therapy daily (n 20) added to PCSK9i, 140 mg twice a month (n 30).

Drug: statin Oral Tablet plus PCSK9i

Interventions

statin Oral Tablet plus PCSK9i DRUG

Patients in the third study cohort will receive for statin oral therapy plus 140 mg twice a month PCSK9i therapy via subcutaneous injection before to practice surgical intervention for carotid artery obstruction.

patients with diabetes mellitus (DM) treated with statin plus PCSK9i

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Study population will be divided in 30 normoglycemics patients vs. 46 DM patients. DM patients will be divided in patients previous treated by oral daily statin therapy (23 patients) vs. DM patients (n 20) previous treated by daily statin therapy plus 140 mg twice a month of PCSK9i. All patients will be affected by severe obstructive carotid artery atherosclerosis.

You may qualify if:

• evidence of carotid artery atherosclerosis with endoluminal stenosis \> 60%;
• aged \>18 years.
• aged \<75 years

You may not qualify if:

• insulin dependent DM;
• absence of carotid artery atherosclerosis with endoluminal stenosis \> 60%;
• contraindication to receive a carotid artery revascularization treatment;
• contraindication to receive metformin treatment;
• controindication to receive PCSK9i treatment;
• neoplastic diseases;

Sponsors & Collaborators

• University of Campania Luigi Vanvitelli: lead

Study Sites (1)

Raffaele Marfella

Naples, 80138, Italy

Location

Biospecimen

Retention: SAMPLES WITH DNA

samples of atherosclerotic plaques obtained during revascularization of carotid arteries.

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Plaque, Atherosclerotic

Interventions

Hydroxymethylglutaryl-CoA Reductase Inhibitors

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Enzyme Inhibitors; Lipid Regulating Agents; Therapeutic Uses

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: clinical professor

Study Record Dates

• First Submitted: May 22, 2019
• First Posted: May 24, 2019
• Study Start: January 1, 2015
• Primary Completion: January 1, 2017
• Study Completion: January 1, 2018
• Last Updated: August 3, 2022

Record last verified: 2022-08

Locations

IT (1)