Effect of Vitis Vinifera Seed Extract on Venous Reflux Time in Varicose Vein

NCT05851183 | Completed Phase 4

• 1 other identifier: VICTORY trial
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

The number of patients with lower extremity varicose veins has been increasing due to an aging population, with treatments divided into conservative and invasive methods. Current treatments can be expensive and inaccessible for some patients. Entelon, a relatively inexpensive intravenous drug, has shown promise in improving symptoms related to venous lymphatic dysfunction, but its objective vascular function improvement hasn't been proven. This study aims to assess the effectiveness of Vitis Vinifera seed extract (Entelon®) combined with lifestyle therapy in patients with varicose veins, using follow-up Doppler ultrasonography to measure venous reflux improvement.

Conditions

Varicose Veins of Lower Limb

Outcome Measures

Primary Outcomes (1)

• Change in venous reflux time

  The investigators will assess the changes in venous reflux time using lower limb venous Doppler ultrasound examinations. The examination will be performed by an independent assessor who is not aware of the group assignments to ensure unbiased assessment and measurement.

  6, 12 weeks

Secondary Outcomes (6)

• Improvement of venous reflux

  6, 12 weeks

• Change in varicose vein size area

  6, 12 weeks

• Change in venous reflux volume

  6, 12 weeks

• Change of extracellular water ratio

  6, 12 weeks

• Improvement in Venous Clinical Severity Score (VCSS)

  6, 12 weeks

Study Arms (2)

Therapeutic lifestyle change

ACTIVE COMPARATOR

Therapeutic lifestyle change only

Behavioral: Therapeutic lifestyle change only

Therapeutic lifestyle change plus Vitis Vinifera extract therapy

EXPERIMENTAL

Therapeutic lifestyle change plus Vitis Vinifera extract medication therapy

Drug: Vitis Vinifera seed extract medication plus therapeutic lifestyle change

Interventions

Vitis Vinifera seed extract medication plus therapeutic lifestyle change DRUG

Administer 150mg of Vitis Vinifera seed extract (Entelon®) orally twice a day

Also known as: Entelon® medication plus therapeutic lifestyle change

Therapeutic lifestyle change plus Vitis Vinifera extract therapy

Therapeutic lifestyle change only BEHAVIORAL

Implementing TLCs is a critical component of a comprehensive treatment plan for varicose veins. A key aspect of TLCs is the optimization of postural habits. Patients are advised to avoid extended sitting or standing periods, which exert additional pressure on the venous system in the lower extremities and exacerbate venous insufficiency. During rest periods, elevating the legs closer to the heart is recommended because this simple yet effective adjustment promotes venous return and reduces the gravitational burden on the venous valves of the legs. The use of graduated compression stockings during waking hours is another therapeutic lifestyle intervention that is often prescribed for patients with varicose veins. Additional TLCs include maintaining optimal body weight and engaging in regular physical exercise Walking or cycling are often recommended because of their effectiveness in promoting lower limb venous return.

Therapeutic lifestyle change

Eligibility Criteria

• Age: 19 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult males and females aged between 19 and under 80 years old
• Patients with the following findings on venous Doppler ultrasound examination:
• Superficial veins (such as the great saphenous vein, small saphenous vein, etc.) showing valvular reflux for 0.5 seconds or longer
• Deep veins (such as the femoral vein, etc.) showing valvular reflux for 1 second or longer
• Patients who have completed the washout period as described below by Visit 2, including the screening period:
• Analgesics, steroids, anti-inflammatory drugs, and venoactive medications (such as Entelon, etc.): at least 4 weeks
• Patients who voluntarily provide written informed consent to participate in this clinical trial

You may not qualify if:

• Peripheral arterial occlusive disease in the lower limbs
• Asymptomatic lower extremity varicose veins
• Acute deep vein thrombosis
• Frequent lower limb pain due to neuropathy
• Patients who have undergone or are scheduled for varicose vein procedures/surgeries (However, patients who have had a procedure or surgery more than 1 year prior to the screening date are eligible to participate)
• Patients diagnosed with systemic diseases causing edema or thrombosis, such as heart failure, endocrine diseases (hypothyroidism, Cushing's syndrome, uncontrolled diabetes), allergic reactions to medications, urticaria and angioedema, malabsorption and protein-calorie malnutrition, obstructive sleep apnea, or thrombophilia, as determined by the investigator
• History of malignancy within the past 5 years, but the following cases are eligible for clinical trial participation:
• Those who have a history within the past 5 years but maintain a cured state without recurrence or metastasis
• Those who have completed treatment for their tumor and have been disease-free for at least 5 years from the screening date
• Those who have passed at least 1 year since the screening date after complete resection of basal cell carcinoma/squamous cell carcinoma, radical resection of thyroid papillary cancer, or successful treatment of cervical intraepithelial neoplasia
• Severe renal dysfunction (serum creatinine levels more than twice the normal upper limit of the institution) at the screening date
• Severe liver dysfunction (ALT or AST levels more than three times the normal upper limit of the institution) at the screening date
• Need to receive diuretics or contraindicated medications and therapies that may affect the results of this clinical trial during the study period (However, patients who have been taking antihypertensive medications (calcium channel blockers, beta-blockers, angiotensin-converting enzyme inhibitors, vasodilators, vasoconstrictors) at the same dosage for at least 4 weeks (28 days) before screening and will maintain the same dosage and administration during the study period are eligible to participate)
• History of clinically significant psychiatric disorders or alcohol abuse
• History of hypersensitivity reactions to the investigational drug or its ingredients

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Yongin Severance Hospitall, Yonsei University College of Medicine

Yongin, Gyeonggi-do, 16995, South Korea

Location

Related Publications (5)

• Gloviczki P, Lawrence PF, Wasan SM, Meissner MH, Almeida J, Brown KR, Bush RL, Di Iorio M, Fish J, Fukaya E, Gloviczki ML, Hingorani A, Jayaraj A, Kolluri R, Murad MH, Obi AT, Ozsvath KJ, Singh MJ, Vayuvegula S, Welch HJ. The 2022 Society for Vascular Surgery, American Venous Forum, and American Vein and Lymphatic Society clinical practice guidelines for the management of varicose veins of the lower extremities. Part I. Duplex Scanning and Treatment of Superficial Truncal Reflux: Endorsed by the Society for Vascular Medicine and the International Union of Phlebology. J Vasc Surg Venous Lymphat Disord. 2023 Mar;11(2):231-261.e6. doi: 10.1016/j.jvsv.2022.09.004. Epub 2022 Oct 12.

  PMID: 36326210 BACKGROUND

• Labropoulos N, Tiongson J, Pryor L, Tassiopoulos AK, Kang SS, Ashraf Mansour M, Baker WH. Definition of venous reflux in lower-extremity veins. J Vasc Surg. 2003 Oct;38(4):793-8. doi: 10.1016/s0741-5214(03)00424-5.

  PMID: 14560232 BACKGROUND

• Labropoulos N, Leon LR Jr. Duplex evaluation of venous insufficiency. Semin Vasc Surg. 2005 Mar;18(1):5-9. doi: 10.1053/j.semvascsurg.2004.12.002.

  PMID: 15791546 BACKGROUND

• De Maeseneer MG, Kakkos SK, Aherne T, Baekgaard N, Black S, Blomgren L, Giannoukas A, Gohel M, de Graaf R, Hamel-Desnos C, Jawien A, Jaworucka-Kaczorowska A, Lattimer CR, Mosti G, Noppeney T, van Rijn MJ, Stansby G, Esvs Guidelines Committee, Kolh P, Bastos Goncalves F, Chakfe N, Coscas R, de Borst GJ, Dias NV, Hinchliffe RJ, Koncar IB, Lindholt JS, Trimarchi S, Tulamo R, Twine CP, Vermassen F, Wanhainen A, Document Reviewers, Bjorck M, Labropoulos N, Lurie F, Mansilha A, Nyamekye IK, Ramirez Ortega M, Ulloa JH, Urbanek T, van Rij AM, Vuylsteke ME. Editor's Choice - European Society for Vascular Surgery (ESVS) 2022 Clinical Practice Guidelines on the Management of Chronic Venous Disease of the Lower Limbs. Eur J Vasc Endovasc Surg. 2022 Feb;63(2):184-267. doi: 10.1016/j.ejvs.2021.12.024. Epub 2022 Jan 11. No abstract available.

  PMID: 35027279 BACKGROUND

• AIUM Practice Parameter for the Performance of a Peripheral Venous Ultrasound Examination. J Ultrasound Med. 2020 May;39(5):E49-E56. doi: 10.1002/jum.15263. Epub 2020 Mar 12. No abstract available.

  PMID: 32162338 BACKGROUND

Study Officials

• In Hyun Jung, MD, PhD

  Yongin Severance Hospital, Yonsei University College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: The study is designed as an open-label trial to investigate the efficacy of vitis vinifera extract compared to a group undergoing lifestyle modification alone.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: The investigators aim to compare and evaluate the improvement effects on venous reflux time in patients with lower extremity varicose veins between lifestyle modifications and the combined treatment of Vitis Vinifera seed extract (Entelon®) administration and lifestyle modifications.

Study Record Dates

• First Submitted: April 28, 2023
• First Posted: May 9, 2023
• Study Start: July 20, 2023
• Primary Completion: September 30, 2024
• Study Completion: January 30, 2025
• Last Updated: March 4, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)