Effects of a Dietary Supplement Composed of Diosmin, Hesperidin, Bromelain, and Ruscus Aculeatus on the Quality of Life in Subjects With Lower Limb Disorders Possibly Prodromal to Chronic Venous Disease

Exclusion Criteria

• •Pregnancy or current breastfeeding; Women of childbearing potential who are not using adequate birth control methods (either hormonal contraception in the form of contraceptive pills, or barrier birth control methods used in combination with a spermicidal product such as foam, gel, or film).
• •\[For the entire duration of the study, women of childbearing potential-defined as those who are less than one year post-menopause or who have not undergone hysterectomy or tubal ligation-must use an effective method of contraception, in accordance with Note 3 of the ICH M3 Guideline. A contraceptive method is considered highly effective if it results in a failure rate of less than 1% per year. Effective contraceptive methods include: hormonal contraceptives containing estrogens and progestins (oral, intravaginal, transdermal) that inhibit ovulation; hormonal contraceptives containing progestins only (oral, injectable, implantable); intrauterine devices (IUDs); hormone-releasing intrauterine systems (IUS); partner vasectomy; sexual abstinence\]; Individuals with chronic venous insufficiency classified as CEAP stages C3-C6 (see Annex 1); Individuals with a positive pitting edema sign detected at Visit 1 after signing the informed consent; Patients with documented deep vein thrombosis within the last 6 months; Current or recent (within the last 4 weeks) use of venoactive and/or anti-edematous products; Individuals scheduled for surgical procedures within 3 months of enrollment; Subjects with a history of heart failure (NYHA Class III-IV), chronic kidney disease, and/or severe hepatic insufficiency; Ongoing oncological or immunosuppressive diseases; Celiac disease; Drug and/or alcohol abuse; Neurological or psychiatric disorders that may impair the validity of informed consent and/or compromise adherence to the study procedures; Known allergy, hypersensitivity, or intolerance to any component of the investigational dietary supplement; Any medical or non-medical condition that, in the opinion of the Investigator, could interfere with the study or make participation unsafe; Subjects currently enrolled in other clinical trials, or who have received another investigational product within 30 days prior to study start; Individuals who have not signed the informed consent form.