AR, IGF-IR, IR and Peripheral Artery Disease

NCT ID: NCT04710186

Last Updated: 2021-01-14

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 30 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-08-01
• Study Completion Date: 2021-03-01

Brief Summary

Peripheral artery Disease (PAD) is a major cardiovascular disease that can impair quality of life (QoL). It affects more often male patients and its pathophysiology is not completely known. Probably androgen receptors and metabolism alteration may play an important role in the onset and in the progression of PAD towards its dreadful complications. The aim of this study is to evaluate the role of Androgen Recetpr , IGF-I receptor, and Insulin Receptor on the arterial wall of male patients with PAD undergoing open revascularization surgery.

Detailed Description

Peripheral artery disease (PAD) of lower limbs is one of the most common clinical manifestation of atherosclerosis and can be considered a major cardiovascular disease with important morbidity and mortality, affecting also quality of life (QoL), thus representing an important public health concern. From a clinical point of view, PAD may be initially symptomatic with intermittent claudication (IC), and in critical limb ischemia (CLI), an advanced stage of PAD, with rest pain, and also with leg skin ulceration, a complication that may even lead to limb loss for amputation. From a pathophysiological point of view, in the presence of atherosclerosis, endothelial activation and dysfunction lead to hemodynamic alterations such as turbulent flow, abnormal shear stress, loss of potential energy, anomalies of vascular tone with functional impairment during leg exercise in early stages, with IC onset, and in advanced stages, during CLI stage, also with rest pain as a result of an important demand/perfusion mismatch. Endothelial dysfunction, and vascular tone are also regulated by sex hormones, and incidence and prevalence of PAD have usually been found to be higher in men than in women, and, more in general, males have a higher risk of developing cardiovascular disease during the reproductive period in comparison with females of the same age. This sex related difference in developing the disease was hypothesized to be related to the protective role of estrogens in female subjects, and harmful effects of androgens in male individuals. Furthermore, the androgen receptor (AR) seems to have a role in neointima formation, in influencing the size and the composition of atherosclerotic plaques, and also vascular smooth muscle cells (VSMCs) activity. Moreover, sex-specific effects on the metabolic system are well-known and associated with different risk profiles for cardiovascular disease and they have been also related to differences in sex hormones activities. In fact, the insulin and IGF-I signaling is mediated by hormone interaction with the insulin receptor (IR) and the IGF-I receptor (IGF-IR) which are members of subclass II of the tyrosine kinase receptor super-family and they, on one hand, participate to the metabolic homeostasis, and on the other hand, they have a direct role on VMMCs, and also in some stages of the atherosclerotic process..

The aim of this study is to evaluate the role of AR, IGF-IR, and IR on the arterial wall of male patients with PAD undergoing open revascularization surgery.

Conditions

Androgen Receptor Abnormal; Insulin-Like Growth Factor I Deficiency; Insulin Receptor, Defect in

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Male patients with PAD

The cohort was built to collect information about the role of androgen receptor, insulin receptor and Insulin-like Growth Factor 1 Receptor (IGF-IR) expression in patients with peripheral artery disease referred to Vascular Surgeon Specialist.

arterial reconstructive open surgery

Intervention Type: PROCEDURE

Patients with peripheral artery disease (PAD) will undergo arterial reconstructive open surgery. Samples obtained from diseased arteries of lower limbs of patients undergoing arterial reconstructive open surgery will be collected and immediately preserved at -80°. Briefly, arterial tissues were excised, homogenized using a motor driven homogenizer and total RNA was isolated using Trizol reagent (Invitrogen, Milan, Italy), in accordance with the manufacturer's instructions. The expression of Androgen Receptor (AR), insulin receptor (IR) and the IGF-I receptor (IGF-IR) will be quantified by real-time PCR using platform Quant Studio7 Flex Real-Time PCR System (Thermo Fisher Scientific, Milan, Italy), following the manufacturer's instructions.

Interventions

arterial reconstructive open surgery

Patients with peripheral artery disease (PAD) will undergo arterial reconstructive open surgery. Samples obtained from diseased arteries of lower limbs of patients undergoing arterial reconstructive open surgery will be collected and immediately preserved at -80°. Briefly, arterial tissues were excised, homogenized using a motor driven homogenizer and total RNA was isolated using Trizol reagent (Invitrogen, Milan, Italy), in accordance with the manufacturer's instructions. The expression of Androgen Receptor (AR), insulin receptor (IR) and the IGF-I receptor (IGF-IR) will be quantified by real-time PCR using platform Quant Studio7 Flex Real-Time PCR System (Thermo Fisher Scientific, Milan, Italy), following the manufacturer's instructions.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Male patients with peripheral artery disease (PAD) eligible to receive arterial reconstructive open surgery.

Exclusion Criteria

• active malignancy
• advanced liver disease
• advanced heart disease

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

University of Catanzaro

OTHER

Sponsor Role: lead

Responsible Party

Prof. Raffaele Serra, MD, Ph.D.

Associate Professor of Vascular Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Raffaele Serra, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University Magna Graecia of Catanzaro

Marcello Maggiolini, M.D.

Role: STUDY_CHAIR

UNICAL - University of Calabria

Locations

University Magna Graecia of Catanzaro

Catanzaro, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Raffaele Serra, M.D., Ph.D.

Role: CONTACT

rserra@unicz.it

+3909613647380

Facility Contacts

Raffaele Serra, M.D., Ph.D.

Role: primary

rserra@unicz.it

+3909613647380

References

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Reference Type: BACKGROUND

PMID: 31303293 (View on PubMed)

Ielapi N, Licastro N, Catana M, Bracale UM, Serra R. Vascular Nursing and Vascular Surgery. Ann Vasc Surg. 2020 Oct;68:522-526. doi: 10.1016/j.avsg.2020.05.038. Epub 2020 May 29.

Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Other Identifiers

ER.ALL.2018.39

Identifier Type: -

Identifier Source: org_study_id