AR, IGF-IR, IR and Peripheral Artery Disease

• Conditions: Insulin-Like Growth Factor I Deficiency; Insulin Receptor, Defect in; Androgen Receptor Abnormal
• Interventions: Procedure: arterial reconstructive open surgery

• Registration Number: NCT04710186
• Lead Sponsor: University of Catanzaro

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.

Study Timeline

• Study Start: 2018-08-01
• Status Verified: 2021-01
• Study First Submitted: 2021-01-11
• Study First Submitted QC: 2021-01-12
• Last Update Submitted: 2021-01-12
• Study First Posted: 2021-01-14
• Last Update Posted: 2021-01-14
• Primary Completion: 2021-02-01
• Study Completion: 2021-03-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Male
• Target Recruitment: 30

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Male patients with PAD	arterial reconstructive open surgery	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.

Primary Outcome Measures

Name	Time	Method
Expression of AR, IGF-IR, IR	at 1year	The expression of IR, IGF-IR and AR was quantified by real-time PCR using platform Quant Studio7 Flex Real-Time PCR System (Thermo Fisher Scientific, Milan, Italy), following the manufacturer's instructions

Trial Locations

Locations (1)

University Magna Graecia of Catanzaro; 🇮🇹 Catanzaro, Italy