Clinical Trial to Assess the Efficacy of µSmin® Plus

Chronic Venous Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04101201
• Other study ID #: CR2019/21
• Status: Completed
• Phase: N/A
• Start date: November 15, 2019
• Est. completion date: April 24, 2020

Study information

• Verified date: June 2020
• Source: Giellepi S.p.A
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 73
• Est. completion date: April 24, 2020
• Est. primary completion date: April 24, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Venous Disease

Intervention

Dietary Supplement:
• µSmin® Plus
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.

Other:
• Placebo
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

Locations

Country	Name	City	State
Romania	SCM Gados	Timisoara	Timis

Sponsors (2)

Lead Sponsor	Collaborator
Giellepi S.p.A	Opera CRO, a TIGERMED Group Company

Country where clinical trial is conducted

Romania, 

References & Publications (20)

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Freag MS, Elnaggar YS, Abdallah OY. Lyophilized phytosomal nanocarriers as platforms for enhanced diosmin delivery: optimization and ex vivo permeation. Int J Nanomedicine. 2013;8:2385-97. doi: 10.2147/IJN.S45231. Epub 2013 Jul 3. — View Citation

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Kakkos SK, Nicolaides AN. Efficacy of micronized purified flavonoid fraction (Daflon®) on improving individual symptoms, signs and quality of life in patients with chronic venous disease: a systematic review and meta-analysis of randomized double-blind placebo-controlled trials. Int Angiol. 2018 Apr;37(2):143-154. doi: 10.23736/S0392-9590.18.03975-5. Epub 2018 Jan 31. Review. — View Citation

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Martinez-Zapata MJ, Vernooij RW, Uriona Tuma SM, Stein AT, Moreno RM, Vargas E, Capellà D, Bonfill Cosp X. Phlebotonics for venous insufficiency. Cochrane Database Syst Rev. 2016 Apr 6;4:CD003229. doi: 10.1002/14651858.CD003229.pub3. Review. — View Citation

Milano G, Leone S, Fucile C, Zuccoli ML, Stimamiglio A, Martelli A, Mattioli F. Uncommon serum creatine phosphokinase and lactic dehydrogenase increase during diosmin therapy: two case reports. J Med Case Rep. 2014 Jun 16;8:194. doi: 10.1186/1752-1947-8-194. — View Citation

Onida S, Davies AH. Predicted burden of venous disease. Phlebology. 2016 Mar;31(1 Suppl):74-9. doi: 10.1177/0268355516628359. Review. — View Citation

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Rabe E, Guex JJ, Morrison N, Ramelet AA, Schuller-Petrovic S, Scuderi A, Staelens I, Pannier F. Treatment of chronic venous disease with flavonoids: recommendations for treatment and further studies. Phlebology. 2013 Sep;28(6):308-19. doi: 10.1177/0268355512471929. Epub 2013 May 6. Review. — View Citation

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Russo R, Chandradhara D, De Tommasi N. Comparative Bioavailability of Two Diosmin Formulations after Oral Administration to Healthy Volunteers. Molecules. 2018 Aug 29;23(9). pii: E2174. doi: 10.3390/molecules23092174. — View Citation

Russo R, Mancinelli A, Ciccone M, Terruzzi F, Pisano C, Severino L. Pharmacokinetic Profile of µSMIN Plus™, a new Micronized Diosmin Formulation, after Oral Administration in Rats. Nat Prod Commun. 2015 Sep;10(9):1569-72. — View Citation

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* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	Patient Global Assessment of the efficacy by scores	Patients satisfaction: 1= very satisfied, 2= satisfied, 3 = adequate, 4= unsatisfied, 5 = very unsatisfied	56 days
Secondary	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
Secondary	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
Secondary	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
Secondary	AE/SAE incidence	Evaluation of safety during all the study period through AE/SAE collection	56 days
Secondary	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