Clinical Trial to Assess the Efficacy of µSmin® Plus

Study Overview
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Brief Summary
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This study evaluates treatment with the dietary supplement µSmin® Plus in a group of patients suffering from chronic venous insufficiency in comparison with a similarly-sized group of patients receiving placebo evaluated by quality of life questionnaires, VAS pain scale, CVI symptomatology, and change in the circumference of the affected leg at calf level

Detailed Description
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In this study we use a dietary supplement - µSmin® Plus - for symptomatic treatment of CVI and we will monitor its impact on CVI symptoms, features, and consequences (item) of the disease listed below: limb edema, walking, daily tasks performance, pain/burning symptoms, pruritus/paresthesis, sensation of heaviness/fatigue, time wasted in the management of the disease, social burden, disease impact on self-confidence, and its impact on physical exercise/recreational activities. Results of related clinical trials were published before showing that this is an active field in clinical reasearch.

Official Title
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Randomized, Double-blind, Placebo-controlled Clinical Trial to Assess the Efficacy of µSmin® Plus (Dietary Supplement) in Chronic Venous Insufficiency Symptoms Relief

Conditions
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Chronic Venous Disease

Intervention / Treatment
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* Dietary Supplement: µSmin® Plus
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female with age ≥18 and ≤60 with chronic venous insufficiency; The chronic venous insufficiency must be graded between C2-C4 on the Clinical-Etiology-Anatomy-Pathophysiology (CEAP) classification system; Able to communicate adequately with the investigator and to comply with the requirements for the entire study; Capable of and freely willing to provide written informed consent prior to participating in the study; Light smokers (<10 cigarettes per day). Exclusion Criteria: Patients suffering from other or associated vascular diseases, diabetes or bleeding disorders; Oedema of the lower limbs of cardiac, renal or hepatic origin; Presence of symptoms and/or trophic disorders of arterial, metabolic, neurological or orthopedic origin including traumas, arthritis, neuropathy; One or more factors likely to affect venous symptoms such as recent childbirth, recent stripping, or deep or superficial venous thrombosis of the lower limbs during the previous 6 months; Obese subjects (BMI > 30); Hypersensitivity to active principles contained in the tested food supplement (diosmin); Patients considered smokers (≥10 cigarettes/day); Patients with concomitant or history of addiction to alcohol, spices or drug abuse; Pregnant women, nursing mothers, or women (only if childbearing potential) not using adequate methods of contraception; Participation in an interventional clinical study in the previous 30 days; Presence of any clinically significant medical condition judged by the investigator to preclude the patient's inclusion in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Diosmin is a naturally occurring flavonoid present in citrus fruits and other plants belonging to the Rutaceae family. It is used for the treatment of chronic venous insufficiency (CVI) for its pheblotonic and vaso-active properties, safety and tolerability as well. µSmin® Plus is a proprietary flavonoid complex with enhanced bio-efficacy. It contains highly concentrated micronized and standardized Diosmin. Highly improved bioavailability and improved oral absorption by micronization of the particles.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: µSmin® Plus<br>µSmin® Plus is a new Micronized Diosmin Formulation for oral administration. Diosmin is extremely well tolerated and safe to use. Diosmin is safe for most people when used short-term for up to 6 months. During the 8 weeks of the clinical investigation, the subject will administer 1 tablet of µSMIN® Plus (corresponding to 450 mg of micronized diosmin) or placebo per day. | Dietary Supplement: µSmin® Plus<br>* µSmin® Plus is a new Micronized Diosmin Formulation for oral administration. Diosmin is extremely well tolerated and safe to use. Diosmin is safe for most people when used short-term for up to 6 months. During the 8 weeks of the clinical investigation, the subject will administer 1 tablet of µSMIN® Plus (corresponding to 450 mg of micronized diosmin) or placebo per day.<br>|
| Placebo Comparator: Placebo<br>It will be supplied by the Sponsor in an amount enough for the duration of the study. The subject will administer 1 tablet per day | Other: Placebo<br>* It will be supplied by the Sponsor in an amount enough for the duration of the study. The subject will administer 1 tablet per day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life assessed | Quality of life is assessed by ChronIc Venous Insuficiency quality of life Questionnaire ( CIVIQ-20 questionnaire ). The 20-item questionnaire, provides a global index and an outline of 4 quality-of-life dimensions-pain (4 items), physical (4 items), psychological (9 items), and social (3 items). Items on the CIVIQ-20 scale were scored from 1 to 5. There are 20 questions in the CIVIQ-20, each with 5 possible answers (1 to 5), the minimum possible score being 20 and the maximum 100. In order to calculate the GIS, the difference between the final score and the minimum possible score is to be divided by the difference between the theoretical maximum and minimum scores (100-20=80), multiplied by 100. A low score will correspond to greater patient comfort. | 56 days | 
| Change in the circumference of each affected leg | To evaluate the efficacy of the dietary supplement µSmin® Plus on ameliorating the symptoms of Chronic Venous Insufficiency in terms of change in the circumference of affected legs and quality of life, in comparison with placebo, from baseline to week 8 visit; The unit for this measurement is centimeter. | 56 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analogue Scale ( VAS scale ) from 0 to 10 for pain measurements | Visual Analogue Scale is a straight horizontal line of 100 mm. The ends are defined as the extreme limits of the pain (symptom, pain, health) orientated from the left (worst) to the right (best). Using a ruler, the score is determined by measuring the distance in millimeters on the 10 centimeters line between the no pain anchor and the patient's mark, providing a range of scores from 0-100. A higher score indicates greater pain intensity and a low score indicates a low pain intensity. | 56 days | 
| Symptoms relief assessed by Venous Clinical Severity Score (VCSS) questionnaire | Venous Clinical Severity Score use the progressive ranking of severity, while weighting the upper levels representing the more severe presentations of Chronical Venous Disease. The lowest possible score is 0=absent meaning that the patient has no symptoms and the highest possible score is 30=sever meaning that the patient has a very severe venous symptoms. | 56 days | 
| Investigator Global Assessment of the efficacy by scoresproduct | Efficacy of treatment: Percentage of physicians who rated 1= excellent, 2 = good, 3= fair, 4= poor | 56 days | 
| Patient Global Assessment of the efficacy by scores | Patients satisfaction: 1= very satisfied, 2= satisfied, 3 = adequate, 4= unsatisfied, 5 = very unsatisfied | 56 days | 
| Percentage of subjects who would want to continue with µSmin® Plus. | By this outcome we want to find out the percentage of patients who will want to continue with µSmin® Plus. | 56 days | 
| Percentage of subjects who experienced symptoms relief | Percentage of subjects who experienced symptoms relief within the first week of intake, within 2 weeks of intake, or more than 2 weeks of intake; | 56 days | 
| Treatment compliance | Variable medication possession ratio (VMPR) will be used to calculate the compliance (or adherence) to the treatment in the two groups collected by diary card and used and unused products | 56 days | 
| AE/SAE incidence | Evaluation of safety during all the study period through AE/SAE collection | 56 days | 
| Investigator Global Assessment of Safety (IGAS): | Investigator Global Assessment of Safety (IGAS): using the 4-point scale:1= very good safety, 2 = good safety, 3 = moderate safety and 4 = poor safety. IGAS will be evaluated at the last visit. | 56 days |