HaemorrhoidsNCT05750563
Randomised, Double-blind, Placebo-controlled to Assess the Efficacy and Safety of the Food Supplement Microsmin® Plus
A study testing diosmin and micronized flavonoids in people with Haemorrhoids, run by Giellepi S.p.A at 1 site in Romania.
Trial summary
Haemorrhoids are variceal dilatations of the anal and perianal venous plexus and often develop secondary to the persistently elevated venous pressure within the haemorrhoidal plexus . Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Haemorrhoids
- What is being tested?
- diosmin and micronized flavonoids
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteRomania
- Study dates
- 28 Feb 2023to 30 Dec 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Men or women aged ≥ 18 and ≤ 60 years. The sex will be balanced by randomized stratification.
- Patients diagnosed with Grade I - II symptomatic haemorrhoids (according to Goligher classification) confirmed by clinical and anoscopic or proctoscopic examination performed within 3 months before baseline. Ultrasound examination at baseline is recommended, but not mandatory.
- Patient free from the following treatments for haemorrhoids from at least 4 weeks: laser treatments for haemorrhoids, steroidal or non-steroidal anti-inflammatory drugs, analgesics (other than the rescue medicine indicated in the protocol), any anti-hemorrhoidal treatment (included phlebotonic compounds both drugs and dietary supplements), anticoagulants, and antiplatelet agents.
- 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.
Who cannot join
- Inflammatory and infectious disease of the digestive tract (e.g., IBD - Inflammatory Bowel Diseases).
- Acute haemorrhoids or complicated haemorrhoids with bleeding requiring admission, such as strangulated internal haemorrhoids, thrombosed internal or external haemorrhoids.
- Previous haemorrhoidectomy or previous laser treatment.
- Moderate to severe hypertension, cardiovascular diseases, renal failure, cirrhosis, colorectal cancer, anal fissure or fistula.
- Use of laser treatments for haemorrhoids, steroidal or non-steroidal anti-inflammatory drugs, analgesics (other than the rescue medicine indicated in the protocol), any anti-hemorrhoidal treatment (included phlebotonic compounds both drugs and dietary supplements), anticoagulants, and antiplatelet agents in the 4 weeks prior to inclusion and during the whole study.
- Alcohol or drug abuse.
Show all 15Show fewer
- Patients considered smokers (≥10 cigarettes/day).
- Energy-restricted diet for weight loss.
- Pregnant woman, lactating woman, and woman of childbearing potential who is planning a pregnancy or is unwilling to use appropriate methods of contraception* during the study.
- Methods of contraception: hormonal contraceptive, intrauterine device or intrauterine system, double barrier method (condom with spermicide/diaphragm or cervical cap with spermicide), surgical sterilization (vasectomy, tubal ligation, etc.).
- Hypersensitivity to active principle (diosmin) or to any other ingredient contained in the tested food supplement.
- History of anaphylaxis or severe complicated allergy symptoms.
- Patients unlikely to cooperate.
- Patients with any other medical condition that, in the opinion of the Investigator, would compromise participation or be likely to lead to hospitalisation during the study.
- Participation in an interventional clinical study or administration of any investigational agents in the previous 30 days.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomised, Double-blind, Placebo-controlled, Parallel-group, Multicentre, Interventional Clinical Trial to Assess the Efficacy and Safety of the Food Supplement Microsmin® Plus in the Symptomatic Treatment of Haemorrhoids
Haemorrhoids are variceal dilatations of the anal and perianal venous plexus and often develop secondary to the persistently elevated venous pressure within the haemorrhoidal plexus .
The classical position of haemorrhoids corresponds to three positions which are the right anterior, right posterior and the left lateral areas of the anal canal. Haemorrhoids may be external or internal. External haemorrhoids are covered with skin and internal haemorrhoids are covered with anal mucous membranes. The grading system used by Banov to classify internal haemorrhoids is one of the most common grading systems used by clinicians and is used to guide therapeutic practice. Internal haemorrhoids can be divided into four categories depending on the degree of prolapse (the protrusion of the haemorrhoid through the anus). The most widely accepted classification is the Goligher classification:
- Bleeding but no prolapse (grade I).
- Hemorrhoidal piles prolapse through the anus during straining, but they reduce spontaneously (grade II).
- Hemorrhoidal piles prolapse through the anus during straining and require manual reduction (grade III).
- The prolapse is irreducible (grade IV). Most symptoms and signs which patients present with arise from internal haemorrhoids, derive from structural changes of the normal anatomic padding (enlarged internal haemorrhoids) and are generally associated with chronic straining either due to constipation, diarrhoea or prolonged periods trying to defecate. They are also common during pregnancy and childbirth.
Read the detailed description
Haemorrhoids are variceal dilatations of the anal and perianal venous plexus and often develop secondary to the persistently elevated venous pressure within the haemorrhoidal plexus .
The classical position of haemorrhoids corresponds to three positions which are the right anterior, right posterior and the left lateral areas of the anal canal. Haemorrhoids may be external or internal. External haemorrhoids are covered with skin and internal haemorrhoids are covered with anal mucous membranes. The grading system used by Banov to classify internal haemorrhoids is one of the most common grading systems used by clinicians and is used to guide therapeutic practice. Internal haemorrhoids can be divided into four categories depending on the degree of prolapse (the protrusion of the haemorrhoid through the anus). The most widely accepted classification is the Goligher classification :
- Bleeding but no prolapse (grade I).
- Hemorrhoidal piles prolapse through the anus during straining, but they reduce spontaneously (grade II).
- Hemorrhoidal piles prolapse through the anus during straining and require manual reduction (grade III).
- The prolapse is irreducible (grade IV). Most symptoms and signs which patients present with arise from internal haemorrhoids, derive from structural changes of the normal anatomic padding (enlarged internal haemorrhoids) and are generally associated with chronic straining either due to constipation, diarrhoea or prolonged periods trying to defecate. They are also common during pregnancy and childbirth.
The acute clinical manifestation of the hemorrhoidal disease (commonly known as "hemorrhoidal crisis") is characterized by symptoms and signs, also common in chronic pathologies, such as rectal bleeding, prolapse, pruritus (itching), pain, oedema, often thrombosis, and less frequently soiling or mucoid discharge. Rectal bleeding (the most common presenting sign) is classically bright red as there is a high blood oxygen content within the arteriovenous anastomosis. This bleeding is usually described as bright red spotting on the toilet tissue or dripping in the toilet bowl and normally occurs at the end of defecation, separately from the stool. External haemorrhoids may be asymptomatic or associated with discomfort or with acute extreme pain in the event of a local thrombosis (formation of a clot).
Phlebotonics are a heterogenous class of drugs consisting of plant extracts (i.e., flavonoids) and synthetic compounds. Although their precise mechanism of action has not been fully established, they are known to strengthen blood vessel walls, improve venous tone, stabilise capillary permeability and increase lymphatic drainage. They have been used to treat a variety of conditions including chronic venous insufficiency, lymphoedema and haemorrhoids. In particular, numerous trials assessing the effect of phlebotonics in treating the symptoms and signs of haemorrhoidal disease (they are generally used in the less severe stages of haemorrhoids, first and second-grade haemorrhoids and during the thrombosis episodes) suggest that there is a potential benefit. Moreover, 2 reviews and 1 systematic review evaluated the micronized purified flavonoid fraction (MPFF) activities and performance in haemorrhoids.
Based on the available clinical evidence, current national guidelines and extensive clinical experience in treating patients affected by the haemorrhoidal disease, MPFF can be administered as a first-line treatment, in combination with diet (increased fibre and fluid intake) and lifestyle modifications, for acute grade I/II HD.
A new micronized formulation of diosmin was incorporated in a new dietary supplement called Microsmin® Plus to increase plasma concentrations due to the property manufacturing process able to improve intestinal absorption following oral intake. This product has evidenced a better bioavailability compared with micronized diosmin in rats (4-fold increased) and in healthy volunteers (19) (9.4 greater with higher plasmatic concentrations).
Moreover, a randomized, double-blind, placebo-controlled trial carried out in patients with chronic venous disease (CVD) showed that the administration of a low dose of Microsmin® Plus is safe and effective in relieving symptoms and improving QoL in patients with CVD after 8 weeks of treatment.
This study aims to investigate the efficacy and safety of phlebotonics (dietary supplement containing micronized diosmin, i.e., Microsmin® Plus) in alleviating the signs, symptoms and severity of haemorrhoidal disease in a set of standard clinical practices where the administration of phlebotonics is integrated with lifestyle counselling. Therefore, the Research Question of the present trial is the following: in a population of adult patients, men and women, suffering from symptomatic haemorrhoids, will the administration of the dietary supplement Microsmin® Plus (diosmin and micronized flavonoids) for 63 days (7-days acute treatment phase + 55-days maintenance phase), integrated with lifestyle counselling, improve the symptomatology (clinical signs and symptoms) in comparison with patients receiving placebo, results observed after 4, 7 and 63 days after the beginning of the treatment?
- Conditions
- Haemorrhoids
- Being tested
- diosmin and micronized flavonoids, Placebo
- Keywords
- haemorrhoids
- Medical subject headings
- Hemorrhoids
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
diosmin and micronized flavonoidsDietary supplement
Also called MICROSMIN® PLUS
the symptomatic treatment of haemorrhoids
PlaceboOther
Use as comparator
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Investigational food supplement placebo will be administered according to the same schedule provided for the active product:
* From day 1 to day 4: 1 tablet three times a day, before meals (breakfast, lunch and dinner)
* From day 5 to day 7: 1 tablet twice a day, before breakfast and dinner
* From day 8 to day 62: 1 tablet once a day, before breakfast Receives: Other: Placebo |
| Experimental | Experimental | The dosage will be the following:
* From day 1 to day 4: 1 tablet three times a day, before meals (breakfast, lunch and dinner)
* From day 5 to day 7: 1 tablet twice a day, before breakfast and dinner
* From day 8 to day 62: 1 tablet once a day, before breakfast Receives: Dietary Supplement: diosmin and micronized flavonoids |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the efficacy of the tested food supplement Microsmin® Plus
Evaluate the efficacy of the tested food supplement Microsmin® Plus (diosmin and micronized flavonoids) in comparison with placebo in the symptomatic treatment of haemorrhoids in adult patients affected by Grade I-II (Goligher classification) haemorrhoids as assessed by the patient at the end of the treatment period.
Measured: 63 days
To evaluate the safety of the tested food supplement through adverse events and serious adverse events incidence assessed by Investigators and reported according to the current legislation
To evaluate the safety of the tested food supplement through AE and SAE incidence assessed by Investigators and reported according to the current legislation.
Measured: 63 days
Secondary outcomes (5)
To evaluate the early efficacy of the tested food supplement in comparison with placebo in the symptomatic treatment of haemorrhoids as assessed by the patient after 4 and 7 days of treatment
To evaluate the early efficacy of the tested food supplement in comparison with placebo in the symptomatic treatment of haemorrhoids as assessed by the patient after 4 and 7 days of treatment.
Measured: 63 days
To evaluate the efficacy of the tested food supplement in comparison with placebo in the clinical improvement of haemorrhoids as assessed by the Investigator at each visit (day 7 and 63)
To evaluate the efficacy of the tested food supplement in comparison with placebo in the clinical improvement of haemorrhoids as assessed by the Investigator at each visit (days 7 and 63).
Measured: 63 days
To evaluate analgesic consumption in patients treated with the tested food supplement in comparison with placebo as reported by the patient in the diary
To evaluate analgesic consumption in patients treated with the tested food supplement in comparison with placebo as reported by the patient in the diary.
Measured: 63 days
To assess the overall satisfaction with the tested food supplement in comparison with placebo according to patient's judgement, at the end of the treatment period (day 63)
To assess the overall satisfaction with the tested food supplement in comparison with placebo according to patient's judgement, at the end of the treatment period (day 63).
Measured: 63 days
To assess the improvement in the quality of life by means of the Short Heath Scale for Hemorrhoidal Disease (SHSHD) score; assessed by patients after 7 and 63 days of treatment
To assess the improvement in the quality of life by means of the Short Heath Scale for Hemorrhoidal Disease (SHSHD) score; assessed by patients after 7 and 63 days of treatment.
Measured: 63 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2023
- Study start28 Feb 2023 (estimated)
- Primary completion15 Oct 2023 (estimated)
- Study completion30 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (43)Papers the sponsor has linked to this study.
- Other trials for HaemorrhoidsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP OF THE FOOD SUPPLEMENT MICROSMIN® PLUS (DIOSMIN AND MICRONIZED FLAVONOIDS)
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Giellepi S.p.A
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Opera CRO, a TIGERMED Group Company
- Responsible party
- Sponsor
- Investigators
- Fabio Terruzzi, CSO, Study director, Giellepi S.p.A
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05750563
- Sponsor's protocol ID
- OPGIE/0122/FS
- Status last verified
- Feb 2023
- First submitted
- 14 Feb 2023
- Last updated
- 1 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lohsiriwat V. Hemorrhoids: from basic pathophysiology to clinical management. World J Gastroenterol. 2012 May 7;18(17):2009-17. doi: 10.3748/wjg.v18.i17.2009.
PubMed 22563187Sanchez C, Chinn BT. Hemorrhoids. Clin Colon Rectal Surg. 2011 Mar;24(1):5-13. doi: 10.1055/s-0031-1272818.
PubMed 22379400Banov L Jr, Knoepp LF Jr, Erdman LH, Alia RT. Management of hemorrhoidal disease. J S C Med Assoc. 1985 Jul;81(7):398-401. No abstract available.
PubMed 3861909Thomson JPS, Goligher JC. Surgery of the anus, rectum and colon. J. C. Goligher. Fourth Edition. 264 × 198 mm. Pp. 968 + vii, with 654 illustrations. 1980. London: Baillière Tindall. £35·00. BJS Br J Surg. 1980;67(7):532-532
Rubbini M, Ascanelli S. Classification and guidelines of hemorrhoidal disease: Present and future. World J Gastrointest Surg. 2019 Mar 27;11(3):117-121. doi: 10.4240/wjgs.v11.i3.117.
PubMed 31057696Perera N, Liolitsa D, Iype S, Croxford A, Yassin M, Lang P, Ukaegbu O, van Issum C. Phlebotonics for haemorrhoids. Cochrane Database Syst Rev. 2012 Aug 15;2012(8):CD004322. doi: 10.1002/14651858.CD004322.pub3.
PubMed 22895941Colak T, Akca T, Dirlik M, Kanik A, Dag A, Aydin S. Micronized flavonoids in pain control after hemorrhoidectomy: a prospective randomized controlled study. Surg Today. 2003;33(11):828-32. doi: 10.1007/s00595-003-2604-5.
PubMed 14605954La Torre F, Nicolai AP. Clinical use of micronized purified flavonoid fraction for treatment of symptoms after hemorrhoidectomy: results of a randomized, controlled, clinical trial. Dis Colon Rectum. 2004 May;47(5):704-10. doi: 10.1007/s10350-003-0119-1. Epub 2004 Mar 25.
PubMed 15037936Corsale I, Carrieri P, Martellucci J, Piccolomini A, Verre L, Rigutini M, Panicucci S. Flavonoid mixture (diosmin, troxerutin, rutin, hesperidin, quercetin) in the treatment of I-III degree hemorroidal disease: a double-blind multicenter prospective comparative study. Int J Colorectal Dis. 2018 Nov;33(11):1595-1600. doi: 10.1007/s00384-018-3102-y. Epub 2018 Jun 22.
PubMed 29934701Cospite M. Double-blind, placebo-controlled evaluation of clinical activity and safety of Daflon 500 mg in the treatment of acute hemorrhoids. Angiology. 1994 Jun;45(6 Pt 2):566-73.
PubMed 8203789Giannini I, Amato A, Basso L, Tricomi N, Marranci M, Pecorella G, Tafuri S, Pennisi D, Altomare DF. Flavonoids mixture (diosmin, troxerutin, hesperidin) in the treatment of acute hemorrhoidal disease: a prospective, randomized, triple-blind, controlled trial. Tech Coloproctol. 2015 Jun;19(6):339-45. doi: 10.1007/s10151-015-1302-9. Epub 2015 Apr 19.
PubMed 25893991Giannini I, Amato A, Basso L, Tricomi N, Marranci M, Pecorella G, Tafuri S, Pennisi D, Altomare DF. Erratum to: Flavonoids mixture (diosmin, troxerutin, hesperidin) in the treatment of acute hemorrhoidal disease: a prospective, randomized, triple-blind, controlled trial. Tech Coloproctol. 2015 Oct;19(10):665-6. doi: 10.1007/s10151-015-1357-7. No abstract available.
PubMed 26338366Jiang ZM, Cao JD. The impact of micronized purified flavonoid fraction on the treatment of acute haemorrhoidal episodes. Curr Med Res Opin. 2006 Jun;22(6):1141-7. doi: 10.1185/030079906X104803.
PubMed 16846547Lyseng-Williamson KA, Perry CM. Micronised purified flavonoid fraction: a review of its use in chronic venous insufficiency, venous ulcers and haemorrhoids. Drugs. 2003;63(1):71-100. doi: 10.2165/00003495-200363010-00005.
PubMed 12487623La Torre F, Nicolai AP, Otti M. [Hemorrhoids and conservative treatment. Review of the literature on the use of diosmin and micronized hesperidin]. Minerva Chir. 1999 Dec;54(12):909-16. No abstract available. Italian.
PubMed 10736998
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomised, Double-blind, Placebo-controlled, Parallel-group, Multicentre, Interventional Clinical Trial to Assess the Efficacy and Safety of the Food Supplement Microsmin® Plus in the Symptomatic Treatment of Haemorrhoids
- ClinicalTrials.gov ID
- NCT05750563
- Acronym / sponsor ID
- OPGIE/0122/FS
- Conditions
- Haemorrhoids
- Keywords
- haemorrhoids
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Giellepi S.p.AIndustry (pharma, biotech, devices)
- Collaborators
- Opera CRO, a TIGERMED Group Company
- Study start
- 28 Feb 2023 (estimated)
- Primary completion
- 15 Oct 2023 (estimated)
- Study completion
- 30 Dec 2023 (estimated)
- First posted
- 1 Mar 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Haemorrhoids are variceal dilatations of the anal and perianal venous plexus and often develop secondary to the persistently elevated venous pressure within the haemorrhoidal plexus .
The classical position of haemorrhoids corresponds to three positions which are the right anterior, right posterior and the left lateral areas of the anal canal. Haemorrhoids may be external or internal. External haemorrhoids are covered with skin and internal haemorrhoids are covered with anal mucous membranes. The grading system used by Banov to classify internal haemorrhoids is one of the most common grading systems used by clinicians and is used to guide therapeutic practice. Internal haemorrhoids can be divided into four categories depending on the degree of prolapse (the protrusion of the haemorrhoid through the anus). The most widely accepted classification is the Goligher classification:
- Bleeding but no prolapse (grade I).
- Hemorrhoidal piles prolapse through the anus during straining, but they reduce spontaneously (grade II).
- Hemorrhoidal piles prolapse through the anus during straining and require manual reduction (grade III).
- The prolapse is irreducible (grade IV). Most symptoms and signs which patients present with arise from internal haemorrhoids, derive from structural changes of the normal anatomic padding (enlarged internal haemorrhoids) and are generally associated with chronic straining either due to constipation, diarrhoea or prolonged periods trying to defecate. They are also common during pregnancy and childbirth.
Detailed description
Haemorrhoids are variceal dilatations of the anal and perianal venous plexus and often develop secondary to the persistently elevated venous pressure within the haemorrhoidal plexus .
The classical position of haemorrhoids corresponds to three positions which are the right anterior, right posterior and the left lateral areas of the anal canal. Haemorrhoids may be external or internal. External haemorrhoids are covered with skin and internal haemorrhoids are covered with anal mucous membranes. The grading system used by Banov to classify internal haemorrhoids is one of the most common grading systems used by clinicians and is used to guide therapeutic practice. Internal haemorrhoids can be divided into four categories depending on the degree of prolapse (the protrusion of the haemorrhoid through the anus). The most widely accepted classification is the Goligher classification :
- Bleeding but no prolapse (grade I).
- Hemorrhoidal piles prolapse through the anus during straining, but they reduce spontaneously (grade II).
- Hemorrhoidal piles prolapse through the anus during straining and require manual reduction (grade III).
- The prolapse is irreducible (grade IV). Most symptoms and signs which patients present with arise from internal haemorrhoids, derive from structural changes of the normal anatomic padding (enlarged internal haemorrhoids) and are generally associated with chronic straining either due to constipation, diarrhoea or prolonged periods trying to defecate. They are also common during pregnancy and childbirth.
The acute clinical manifestation of the hemorrhoidal disease (commonly known as "hemorrhoidal crisis") is characterized by symptoms and signs, also common in chronic pathologies, such as rectal bleeding, prolapse, pruritus (itching), pain, oedema, often thrombosis, and less frequently soiling or mucoid discharge. Rectal bleeding (the most common presenting sign) is classically bright red as there is a high blood oxygen content within the arteriovenous anastomosis. This bleeding is usually described as bright red spotting on the toilet tissue or dripping in the toilet bowl and normally occurs at the end of defecation, separately from the stool. External haemorrhoids may be asymptomatic or associated with discomfort or with acute extreme pain in the event of a local thrombosis (formation of a clot).
Phlebotonics are a heterogenous class of drugs consisting of plant extracts (i.e., flavonoids) and synthetic compounds. Although their precise mechanism of action has not been fully established, they are known to strengthen blood vessel walls, improve venous tone, stabilise capillary permeability and increase lymphatic drainage. They have been used to treat a variety of conditions including chronic venous insufficiency, lymphoedema and haemorrhoids. In particular, numerous trials assessing the effect of phlebotonics in treating the symptoms and signs of haemorrhoidal disease (they are generally used in the less severe stages of haemorrhoids, first and second-grade haemorrhoids and during the thrombosis episodes) suggest that there is a potential benefit. Moreover, 2 reviews and 1 systematic review evaluated the micronized purified flavonoid fraction (MPFF) activities and performance in haemorrhoids.
Based on the available clinical evidence, current national guidelines and extensive clinical experience in treating patients affected by the haemorrhoidal disease, MPFF can be administered as a first-line treatment, in combination with diet (increased fibre and fluid intake) and lifestyle modifications, for acute grade I/II HD.
A new micronized formulation of diosmin was incorporated in a new dietary supplement called Microsmin® Plus to increase plasma concentrations due to the property manufacturing process able to improve intestinal absorption following oral intake. This product has evidenced a better bioavailability compared with micronized diosmin in rats (4-fold increased) and in healthy volunteers (19) (9.4 greater with higher plasmatic concentrations).
Moreover, a randomized, double-blind, placebo-controlled trial carried out in patients with chronic venous disease (CVD) showed that the administration of a low dose of Microsmin® Plus is safe and effective in relieving symptoms and improving QoL in patients with CVD after 8 weeks of treatment.
This study aims to investigate the efficacy and safety of phlebotonics (dietary supplement containing micronized diosmin, i.e., Microsmin® Plus) in alleviating the signs, symptoms and severity of haemorrhoidal disease in a set of standard clinical practices where the administration of phlebotonics is integrated with lifestyle counselling. Therefore, the Research Question of the present trial is the following: in a population of adult patients, men and women, suffering from symptomatic haemorrhoids, will the administration of the dietary supplement Microsmin® Plus (diosmin and micronized flavonoids) for 63 days (7-days acute treatment phase + 55-days maintenance phase), integrated with lifestyle counselling, improve the symptomatology (clinical signs and symptoms) in comparison with patients receiving placebo, results observed after 4, 7 and 63 days after the beginning of the treatment?
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP OF THE FOOD SUPPLEMENT MICROSMIN® PLUS (DIOSMIN AND MICRONIZED FLAVONOIDS)
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: PlaceboInvestigational food supplement placebo will be administered according to the same schedule provided for the active product: * From day 1 to day 4: 1 tablet three times a day, before meals (breakfast, lunch and dinner) * From day 5 to day 7: 1 tablet twice a day, before breakfast and dinner * From day 8 to day 62: 1 tablet once a day, before breakfast |
| Experimental | Experimental | Dietary Supplement: diosmin and micronized flavonoidsThe dosage will be the following: * From day 1 to day 4: 1 tablet three times a day, before meals (breakfast, lunch and dinner) * From day 5 to day 7: 1 tablet twice a day, before breakfast and dinner * From day 8 to day 62: 1 tablet once a day, before breakfast |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Men or women aged ≥ 18 and ≤ 60 years. The sex will be balanced by randomized stratification.
- Patients diagnosed with Grade I - II symptomatic haemorrhoids (according to Goligher classification) confirmed by clinical and anoscopic or proctoscopic examination performed within 3 months before baseline. Ultrasound examination at baseline is recommended, but not mandatory.
- Patient free from the following treatments for haemorrhoids from at least 4 weeks: laser treatments for haemorrhoids, steroidal or non-steroidal anti-inflammatory drugs, analgesics (other than the rescue medicine indicated in the protocol), any anti-hemorrhoidal treatment (included phlebotonic compounds both drugs and dietary supplements), anticoagulants, and antiplatelet agents.
- 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.
Key exclusion criteria (15 listed)
- Inflammatory and infectious disease of the digestive tract (e.g., IBD - Inflammatory Bowel Diseases).
- Acute haemorrhoids or complicated haemorrhoids with bleeding requiring admission, such as strangulated internal haemorrhoids, thrombosed internal or external haemorrhoids.
- Previous haemorrhoidectomy or previous laser treatment.
- Moderate to severe hypertension, cardiovascular diseases, renal failure, cirrhosis, colorectal cancer, anal fissure or fistula.
- Use of laser treatments for haemorrhoids, steroidal or non-steroidal anti-inflammatory drugs, analgesics (other than the rescue medicine indicated in the protocol), any anti-hemorrhoidal treatment (included phlebotonic compounds both drugs and dietary supplements), anticoagulants, and antiplatelet agents in the 4 weeks prior to inclusion and during the whole study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| diosmin and micronized flavonoidsAlso: MICROSMIN® PLUSthe symptomatic treatment of haemorrhoids | Dietary supplement | Experimental |
| PlaceboUse as comparator | Other | Placebo |
Primary outcome
To evaluate the efficacy of the tested food supplement Microsmin® Plus
Time frame: 63 days
Evaluate the efficacy of the tested food supplement Microsmin® Plus (diosmin and micronized flavonoids) in comparison with placebo in the symptomatic treatment of haemorrhoids in adult patients affected by Grade I-II (Goligher classification) haemorrhoids as assessed by the patient at the end of the treatment period.
To evaluate the safety of the tested food supplement through adverse events and serious adverse events incidence assessed by Investigators and reported according to the current legislation
Time frame: 63 days
To evaluate the safety of the tested food supplement through AE and SAE incidence assessed by Investigators and reported according to the current legislation.
5 secondary outcomes
To evaluate the early efficacy of the tested food supplement in comparison with placebo in the symptomatic treatment of haemorrhoids as assessed by the patient after 4 and 7 days of treatment
Time frame: 63 days
To evaluate the efficacy of the tested food supplement in comparison with placebo in the clinical improvement of haemorrhoids as assessed by the Investigator at each visit (day 7 and 63)
Time frame: 63 days
To evaluate analgesic consumption in patients treated with the tested food supplement in comparison with placebo as reported by the patient in the diary
Time frame: 63 days
To assess the overall satisfaction with the tested food supplement in comparison with placebo according to patient's judgement, at the end of the treatment period (day 63)
Time frame: 63 days
To assess the improvement in the quality of life by means of the Short Heath Scale for Hemorrhoidal Disease (SHSHD) score; assessed by patients after 7 and 63 days of treatment
Time frame: 63 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2023.
- Background: PubMed 22563187Lohsiriwat V. Hemorrhoids: from basic pathophysiology to clinical management. World J Gastroenterol. 2012 May 7;18(17):2009-17. doi: 10.3748/wjg.v18.i17.2009.
- Background: PubMed 22379400Sanchez C, Chinn BT. Hemorrhoids. Clin Colon Rectal Surg. 2011 Mar;24(1):5-13. doi: 10.1055/s-0031-1272818.
- Background: PubMed 3861909Banov L Jr, Knoepp LF Jr, Erdman LH, Alia RT. Management of hemorrhoidal disease. J S C Med Assoc. 1985 Jul;81(7):398-401. No abstract available.
- BackgroundThomson JPS, Goligher JC. Surgery of the anus, rectum and colon. J. C. Goligher. Fourth Edition. 264 × 198 mm. Pp. 968 + vii, with 654 illustrations. 1980. London: Baillière Tindall. £35·00. BJS Br J Surg. 1980;67(7):532-532
- Background: PubMed 31057696Rubbini M, Ascanelli S. Classification and guidelines of hemorrhoidal disease: Present and future. World J Gastrointest Surg. 2019 Mar 27;11(3):117-121. doi: 10.4240/wjgs.v11.i3.117.
- Background: PubMed 22895941Perera N, Liolitsa D, Iype S, Croxford A, Yassin M, Lang P, Ukaegbu O, van Issum C. Phlebotonics for haemorrhoids. Cochrane Database Syst Rev. 2012 Aug 15;2012(8):CD004322. doi: 10.1002/14651858.CD004322.pub3.
- Background: PubMed 14605954Colak T, Akca T, Dirlik M, Kanik A, Dag A, Aydin S. Micronized flavonoids in pain control after hemorrhoidectomy: a prospective randomized controlled study. Surg Today. 2003;33(11):828-32. doi: 10.1007/s00595-003-2604-5.
- Background: PubMed 15037936La Torre F, Nicolai AP. Clinical use of micronized purified flavonoid fraction for treatment of symptoms after hemorrhoidectomy: results of a randomized, controlled, clinical trial. Dis Colon Rectum. 2004 May;47(5):704-10. doi: 10.1007/s10350-003-0119-1. Epub 2004 Mar 25.
- Background: PubMed 29934701Corsale I, Carrieri P, Martellucci J, Piccolomini A, Verre L, Rigutini M, Panicucci S. Flavonoid mixture (diosmin, troxerutin, rutin, hesperidin, quercetin) in the treatment of I-III degree hemorroidal disease: a double-blind multicenter prospective comparative study. Int J Colorectal Dis. 2018 Nov;33(11):1595-1600. doi: 10.1007/s00384-018-3102-y. Epub 2018 Jun 22.
- Background: PubMed 8203789Cospite M. Double-blind, placebo-controlled evaluation of clinical activity and safety of Daflon 500 mg in the treatment of acute hemorrhoids. Angiology. 1994 Jun;45(6 Pt 2):566-73.
- Background: PubMed 25893991Giannini I, Amato A, Basso L, Tricomi N, Marranci M, Pecorella G, Tafuri S, Pennisi D, Altomare DF. Flavonoids mixture (diosmin, troxerutin, hesperidin) in the treatment of acute hemorrhoidal disease: a prospective, randomized, triple-blind, controlled trial. Tech Coloproctol. 2015 Jun;19(6):339-45. doi: 10.1007/s10151-015-1302-9. Epub 2015 Apr 19.
- Background: PubMed 26338366Giannini I, Amato A, Basso L, Tricomi N, Marranci M, Pecorella G, Tafuri S, Pennisi D, Altomare DF. Erratum to: Flavonoids mixture (diosmin, troxerutin, hesperidin) in the treatment of acute hemorrhoidal disease: a prospective, randomized, triple-blind, controlled trial. Tech Coloproctol. 2015 Oct;19(10):665-6. doi: 10.1007/s10151-015-1357-7. No abstract available.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Fabio Terruzzi, CSO study director
Giellepi S.p.A
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing diosmin and micronized flavonoids in people with Haemorrhoids, run by Giellepi S.p.A at 1 site in Romania.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Romania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Dionisio F. Barattini, MD (+39 3355437574, barattini@operacro.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate the efficacy of the tested food supplement Microsmin® Plus (time frame: 63 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05750563, which also lists 43 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Mar 2023.