Lipid Peroxidation and Options Antioxidant Therapy for Secondary Lymphedema of the Lower Extremities

A single-center, open, prospective, randomized, controlled clinical trial will include 120 patients with lower limb lymphedema who undergo treatment in an office-based vascular lab at the Ryazan regional clinical cardiology dispensary, Ryazan, Russia. The patients will be recruited by the staff of the Department of cardiovascular, endovascular, operative surgery, and topographic anatomy, Ryazan state I.P. Pavlov medical university, Russia. The study will include patients who meet the inclusion criteria and do not meet the exclusion criteria. Patients will be divided into 4 groups, 30 subjects each. Group 1-patients with lower limb lymphedema who will receive conservative therapy with elastic compression and an antioxidant (Tocopherol-400 IU/day); Group 2-patients with lower limb lymphedema who will receive conservative therapy with Micronised purified flavonoid fraction (diosmin+flavonoids expressed as hesperidin)-1000mg/day) in addition to elastic compression; Group 3-patients with lower limb lymphedema who will be treated with elastic compression; Group 4- healthy volunteers with no history or clinical signs of venous or lymphatic disease; The duration of this study for each subject will be a maximum of 90 days. Pre-screening and screening will involve 200 subjects with a total of 120 subjects who will be randomized into the study. Peripheral blood samples will be collected to evaluate the activity of biochemical markers of endothelial function; the quality of life will also be assessed.

Study Overview

• Status: Completed
• Conditions: Lower Extremity Lymphedema
• Intervention / Treatment: Drug: Tocopherol; Drug: Micronised purified flavonoid fraction (diosmin+flavonoids expressed as hesperidin); Other: Elastic compression

Detailed Description

Research methods:

1. Physical examination;
2. peripheral blood sampling (assessment of the concentration of the markers of endothelial dysfunction, including malondialdehyde (MDA), superoxide dismutase (SD), catalase( CAT), glutathione peroxidase (GP). MDA concentration will be determined with a competitive enzyme immunoassay (ELISA), which will be performed using a General MDA assessment kit (manufacturer: USCN Life Science Inc. US-CEA597GE). CAT concentration will be determined using a competitive enzyme immunoassay (ELISA), which will be performed with a kit for quantitative in vitro assessment of catalase (manufacturer: USCN Life Science Inc. US-SEC418Hu). GP concentration will be determined with a competitive enzyme immunoassay (ELISA), which will be performed using a glutathione peroxidase quantification set (abfrontier supplier, Republic of Korea - LF- EK0110). SOD concentration will be determined using a competitive enzyme immunoassay (ELISA), which will be performed using a total superoxide dismutase detection kit (supplier Cayman Chemical Company, US - 706002).
3. Lower limb venous sonography with a linear 5-13 MHz probe;
4. Patient questionnaire using a Russian-language version of the Quality of life questionnaire "SF-36 Health Status Survey"

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• Russian Federation
  • Ryazan', Russian Federation, 390026
    • Ryazan State Medical University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Secondary lymphedema of the lower extremities
• Signed Informed Consent Form

Exclusion Criteria:

• varicose veins of the lower extremities,
• deep vein thrombosis,
• post-thrombotic disease,
• obliterating
• atherosclerosis of the lower limb arteries,
• pregnancy,
• lactation,
• cancer,
• acute violation of cerebral circulation in the anamnesis,
• trophic lesions of the skin of the lower extremities,
• diabetes mellitus
• an infectious disease with a history of three months prior to inclusion in the study,
• heart failure,
• kidney failure,
• pulmonary insufficiency.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tocopherol; patients with lower limb lymphedema who will receive conservative therapy with elastic compression and an antioxidant (Tocopherol-400 IU/day) - 90 days	Drug: Tocopherol; patients with lower limb lymphedema receiving conservative therapy (elastic compression, to which are added preparations with antioxidant endotheliotropic activity (Tocopherol-400 IU/day)
Experimental: Micronised purified flavonoid fraction; patients with lower limb lymphedema who will receive conservative therapy with Micronised purified flavonoid fraction (diosmin+flavonoids expressed as hesperidin)-1000mg/day) in addition to elastic compression - 90 days	Drug: Micronised purified flavonoid fraction (diosmin+flavonoids expressed as hesperidin); Micronised purified flavonoid fraction (diosmin+flavonoids expressed as hesperidin) is prescribed at a dose of 1000 mg / day Tocopherol is prescribed at a dose of 400 ME/ day
Other: Elastic compression; patients with lower limb lymphedema who will be treated with elastic compression - 90 days	Other: Elastic compression; patients with lower limb lymphedema receiving conservative therapy that includes only the use of elastic compression
No Intervention: Healthy volunteers; healthy volunteers with no history or clinical signs of venous or lymphatic disease - 90 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The malleolar volume of the limb	The circumference at the level of the narrowest part of the lower leg, measured in centimeters	90 days
The Level Of Catalase	Biochemical indicator of the functional state of the endothelium. Catalase concentration will be determined using a competitive enzyme immunoassay (ELISA), which will be performed with a kit for quantitative in vitro assessment of catalase (manufacturer: USCN Life Science Inc. US-SEC418Hu). Unit of measurement ng / ml	90 days
The Level Of Superoxide Dismutase	Biochemical indicator of the functional state of the endothelium. Superoxide Dismutase concentration will be determined using a competitive enzyme immunoassay (ELISA), which will be performed using a total superoxide dismutase detection kit (supplier Cayman Chemical Company, US - 706002). Unit of measurement UI / ml	90 days
The Level Of Glutathione Peroxidase	Biochemical indicator of the functional state of the endothelium. Glutathione Peroxidase concentration will be determined with a competitive enzyme immunoassay (ELISA), which will be performed using a glutathione peroxidase quantification set (abfrontier supplier, Republic of Korea - LF- EK0110). Unit of measurement ng / ml	90 days
The level of Malondialdehyde	Biochemical indicator of the functional state of the endothelium. Malondialdehyde concentration will be determined with a competitive enzyme immunoassay (ELISA), which will be performed using a General MDA assessment kit (manufacturer: USCN Life Science Inc. US-CEA597GE). Unit of measurement ng / ml	90 days
Quality of life indicators: questionnaire	Patient questionnaire using a Russian-language version of the Quality of life questionnaire "Short Form-36 Health Status Survey". 8 indicators. Indicator from 0 to 100. Higher scores mean a better outcome.	90 days

Collaborators and Investigators

• Sponsor: Ryazan State Medical University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2019
• Primary Completion (Actual): August 3, 2022
• Study Completion (Actual): August 3, 2022

Study Registration Dates

• First Submitted: April 18, 2020
• First Submitted That Met QC Criteria: April 23, 2020
• First Posted (Actual): April 24, 2020

Study Record Updates

• Last Update Posted (Actual): August 4, 2022
• Last Update Submitted That Met QC Criteria: August 3, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: endothelial dysfunction; antioxidants; secondary lymphedema of the lower extremities; micronized purified flavonoid fraction
• Additional Relevant MeSH Terms: Lymphatic Diseases; Lymphedema; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Vitamin E; Tocopherols; alpha-Tocopherol; Tocotrienols
• Other Study ID Numbers: MDA-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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