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

Inclusion criteria

• Both sexes;
• Age ≥18 years;
• Signed informed consent form for participation in the study;
• Presence of at least one clinical symptom possibly related to chronic venous disease (such as heaviness and/or swelling and/or pain in the lower limbs, nighttime cramps, tired/heavy legs, itching, burning and/or warmth, tingling, or restlessness in the lower limbs);
• Willingness to participate in the study and to comply with the study procedures, as confirmed by signing the written informed consent.

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.