Effects of Bioflavanoids on Vascular Wall Remodeling in Patients With Varicose Veins

Study of the Effects of Bioflavonoids on Venous Wall Remodeling in Patients With Varicose Veins of the Lower Extremities

The study is aimed at assessing the dynamics of changes in biochemical markers of venous wall remodeling (type 1 plasminogen activation inhibitor (PAI-1), fibronectin (fibronectin, FN), vimentin (vimentin, VM), von Willebrand factor (vWF), PECAM-1 (CD31) ) in patients with C2s-C3s varicose veins compared with healthy volunteers while taking Venarus® (diosmin in combination with hesperidin).

Study Overview

• Status: Active, not recruiting
• Conditions: Vascular Diseases; Varicose Veins of Lower Limb; Leg Edema; Varix
• Intervention / Treatment: Drug: "Venarus®" (diosmin and hesperidin); Other: Elastic compression; Other: Evaluation of biomarkers of venous wall remodeling (fibronectin, PAI-1, vimentin, vWF, CD31), venous symptoms and severity scores; Procedure: Endovenous laser ablation (EVLA) with miniphlebectomy

Detailed Description

The study will include 80 patients with varicose veins of the lower extremities, CEAP (CEAP classification stands for Clinical (C), Etiological (E), Anatomical (A), and Pathophysiological (P)) clinical class C2s-C3s and 20 healthy volunteers of similar age, gender, and ethnicity (100 patients altogether). The study participants will be divided into five groups: Group A: 20 patients with varicose veins who will be treated conservatively - receive the drug "Venarus®" (diosmin in combination with hesperidin) at a dosage of 1000 mg once daily for 6 months; Group B: 20 patients with varicose veins C2s-C3s who are not prescribed conservative therapy with venoactive drugs and will not undergo invasive treatment; Group C: 20 patients with varicose veins who will undergo invasive treatment (endovenous laser ablation with miniphlebectomy), followed by Venarus at a dosage of 1000 mg once daily for 6 months; Group D: 20 patients with varicose veins who will undergo invasive treatment (endovenous laser ablation with miniphlebectomy), after which no venoactive drugs will be prescribed. Group E: 20 healthy volunteers without clinical and ultrasound signs of varicose veins.

All subjects in groups A, B, C, and D will receive elastic compression.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Russian Federation
  • Ryazan, Russian Federation
    • RyazanSMU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• The study will include men or women over 18 years of age with varicose disease of the lower extremities C2-C3 according to the CEAP classification, confirmed by ultrasound duplex scanning of the veins of the lower extremities

Exclusion Criteria:

• the presence of neoplasms, previous operations on the vessels of the lower extremities, deep vein thrombosis, severe concomitant diseases, including infectious ones, pregnancy, lactation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: А- Varicose vein patients with Conservative treatment with a venoactive drug; 20 patients with varicose veins who will be treated conservatively - receive the drug "Venarus®" (diosmin in combination with hesperidin) at a dosage of 1000 mg once daily for 6 months along with elastic compression	Drug: "Venarus®" (diosmin and hesperidin); "Venarus®" (diosmin and hesperidin) at a dosage of 1000 mg once daily for 6 months; Other Names: BIOFLAVANOIDS; Other: Elastic compression; All subject with varicose veins enrolled in the study will receive class 2 elastic compression (elastic stockings) after enrollment; Other: Evaluation of biomarkers of venous wall remodeling (fibronectin, PAI-1, vimentin, vWF, CD31), venous symptoms and severity scores; The patients and healthy volunteers will undergo evaluation of biomarkers of venous wall remodeling (fibronectin, PAI-1, vimentin, vWF, CD31), Venous clinical severity (VCS) score, Visual Analog Scale (VAS) score and 20 item-ChronIc Venous dIsease quality-of-life Questionnaire (CIVIQ-20) at baseline, and 2, 3, and 6 months after enrollment
Experimental: B- Varicose veins patients without invasive treatment or a venoactive drug; 20 patients with varicose veins C2s-C3s who are not prescribed conservative therapy with a venoactive drug and will not undergo invasive treatment; the patients will receive elastic compression	Other: Elastic compression; All subject with varicose veins enrolled in the study will receive class 2 elastic compression (elastic stockings) after enrollment; Other: Evaluation of biomarkers of venous wall remodeling (fibronectin, PAI-1, vimentin, vWF, CD31), venous symptoms and severity scores; The patients and healthy volunteers will undergo evaluation of biomarkers of venous wall remodeling (fibronectin, PAI-1, vimentin, vWF, CD31), Venous clinical severity (VCS) score, Visual Analog Scale (VAS) score and 20 item-ChronIc Venous dIsease quality-of-life Questionnaire (CIVIQ-20) at baseline, and 2, 3, and 6 months after enrollment
Experimental: C- Varicose veins patients who will undergo EVLA and conservative treatment with a venoactive drug; 20 patients with varicose veins who will undergo invasive treatment (endovenous laser ablation with miniphlebectomy), followed by Venarus at a dosage of 1000 mg once daily for 6 months; the patients will also receive elastic compression	Drug: "Venarus®" (diosmin and hesperidin); "Venarus®" (diosmin and hesperidin) at a dosage of 1000 mg once daily for 6 months; Other Names: BIOFLAVANOIDS; Other: Elastic compression; All subject with varicose veins enrolled in the study will receive class 2 elastic compression (elastic stockings) after enrollment; Other: Evaluation of biomarkers of venous wall remodeling (fibronectin, PAI-1, vimentin, vWF, CD31), venous symptoms and severity scores; The patients and healthy volunteers will undergo evaluation of biomarkers of venous wall remodeling (fibronectin, PAI-1, vimentin, vWF, CD31), Venous clinical severity (VCS) score, Visual Analog Scale (VAS) score and 20 item-ChronIc Venous dIsease quality-of-life Questionnaire (CIVIQ-20) at baseline, and 2, 3, and 6 months after enrollment; Procedure: Endovenous laser ablation (EVLA) with miniphlebectomy; Endovenous laser ablation will be performed under local and tumescent anesthesia, laser wavelength 1470nm.
Experimental: D- Varicose veins patients who will undergo EVLA; 20 patients with varicose veins patients who will undergo invasive treatment (EVLK with miniphlebectomy), after which no venoactive drugs will be prescribed; the patients will also receive elastic compression	Other: Elastic compression; All subject with varicose veins enrolled in the study will receive class 2 elastic compression (elastic stockings) after enrollment; Other: Evaluation of biomarkers of venous wall remodeling (fibronectin, PAI-1, vimentin, vWF, CD31), venous symptoms and severity scores; The patients and healthy volunteers will undergo evaluation of biomarkers of venous wall remodeling (fibronectin, PAI-1, vimentin, vWF, CD31), Venous clinical severity (VCS) score, Visual Analog Scale (VAS) score and 20 item-ChronIc Venous dIsease quality-of-life Questionnaire (CIVIQ-20) at baseline, and 2, 3, and 6 months after enrollment; Procedure: Endovenous laser ablation (EVLA) with miniphlebectomy; Endovenous laser ablation will be performed under local and tumescent anesthesia, laser wavelength 1470nm.
Experimental: E-healthy volunteers; 20 healthy volunteers without clinical and ultrasound signs of varicose veins receiving no treatment	Other: Evaluation of biomarkers of venous wall remodeling (fibronectin, PAI-1, vimentin, vWF, CD31), venous symptoms and severity scores; The patients and healthy volunteers will undergo evaluation of biomarkers of venous wall remodeling (fibronectin, PAI-1, vimentin, vWF, CD31), Venous clinical severity (VCS) score, Visual Analog Scale (VAS) score and 20 item-ChronIc Venous dIsease quality-of-life Questionnaire (CIVIQ-20) at baseline, and 2, 3, and 6 months after enrollment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes in biomarkers of venous wall remodeling	Changes in biomarkers of venous wall remodeling including vimentin, fibronectin, PAI-1, vWF, CD31	At baseline, and at 2, 3 and 6 months after the start of treatment
Changes in biomarkers expression in venous wall	Changes in expression of biomarkers of venous wall remodeling (vimentin, fibronectin, PAI-1, vWF, CD31) as assessed with Western blot techniques using the dilated veins harvested during miniphlebectomy	6 months

Collaborators and Investigators

• Sponsor: Ryazan State Medical University
• Investigators: Principal Investigator: Igor Suchkov, RyazSMU

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2023
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: October 2, 2023
• First Submitted That Met QC Criteria: April 14, 2024
• First Posted (Actual): April 16, 2024

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 14, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: varicose veins; bioflavonoids; venous remodeling
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Varicose Veins
• Other Study ID Numbers: RyazanSMU

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No