Monocultivar Coratina Extra Virgin Olive Oil in UC Patients (EVORCU)

• ClinicalTrials.gov Identifier: NCT03408847
• Recruitment Status: Unknown
• First Posted: January 24, 2018
• Last Update Posted: February 7, 2018
• Sponsor: Casa Sollievo della Sofferenza IRCCS
• Collaborator: Fondazione Schena
• Information provided by (Responsible Party): Angelo Andriulli, Casa Sollievo della Sofferenza IRCCS

Study Description

Brief Summary:

Epidemiological studies suggest that daily intake of fruits and vegetables high in polyphenols or the addition of olive oil containing many polyphenols is associated with a reduced risk of chronic diseases including cardiovascular, metabolic, neurodegenerative, and inflammatory bowel conditions.

In vivo experiments demonstrated that the administration of a diet associated with daily intake of extra virgin olive oil (EVOO) reduces histological lesions and symptomatology in rats with a dextran sulfate sodium (DDS) induced colitis. A diet supplemented with hydroxytyrosol (a component of olive oil) showed a reduction of the inflammatory process at the inflamed colon of the rats.

Condition or disease	Intervention/treatment	Phase
Ulcerative Colitis Chronic Mild	Combination Product: Beclomethasone dipropionate in addition to MC-EVOO; Combination Product: Beclomethasone dipropionate in addition to refined oil	Not Applicable

Detailed Description:

Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology, which usually occurs in young adults (II-IV decade of life).

Epidemiological data have shown a north-south gradient of both incidence and prevalence of UC in European countries, with a higher prevalence in northern European countries than in the Mediterranean area. However, recent data show a reduction in these differences in the last two decades. The reasons of this reduction are unknown, but it is possible that these differences are related to a change in dietary habits in southern European countries where a diet rich in fresh fruits and vegetables (the so-called "Mediterranean diet") is gradually being replaced by a typical diet of the industrialized countries of northern Europe, characterized by high consumption of frozen or pre-packaged foods of the food industry.

These changes in the diet regime have also replaced the type of oil contained in foods, ranging from olive oil (typical of the Mediterranean diet) to fats of animal origin or vegetable oils not coming from the olives.

Olive oil is universally recognized as the symbol of the Mediterranean diet and its beneficial properties have been extensively studied.

In particular, there are scientific evidence showing an effect of virgin olive oil on the lipid metabolism, on chronic inflammation, on blood pressure, and the regulation and detoxification of free radicals.

In particular, beneficial effects would in part be related to polyphenols, potent natural antioxidants contained in olive oil.

Monocultivar Coratina extra virgin olive oil (MC-EVOO) is an Apulian olive oil that, while possessing an extraordinary health effect superior to other cultivars, is not very used because of its distinctive characteristics of bitter and spicy. The bitter and the spicy of the extra virgin olive oil obtained from Coratina monocultivar are not defects in the oil but are the expression of a very high concentration of polyphenols (up to 800-1000 mg / kg of oil) compared to other varieties which, as well as providing extraordinary health benefits to the consumer, extend the expiration date of the oil itself, preserving it from oxidative action.

The MC-EVOO is a typical of the Apulia Region and it is characterized by:

1. high content of polyphenols
2. natural 100% product, with no residues of chemical solvents and other toxic and harmful contaminants.

No studies have been published so far that have demonstrated a potential toxic effects of polyphenols. Instead, EVOO-C supplementation could potentially have positive effects on lipid metabolism and body weight.

Epidemiological studies suggest that daily intake of fruits and vegetables high in polyphenols or the addition of olive oil containing many polyphenols is associated with a reduced risk of chronic diseases including cardiovascular, inflammatory, metabolic, neurodegenerative, and some neoplasms.

Also the results of in vitro study showed these properties but these results have to be carefully evaluated because in vivo the polyphenols, after being absorbed into the intestine and conjugated in the liver, arrive in the blood in methylated, sulphated and glycogenated form.

These molecules are completely different from the structural point of view of native molecules. Moreover, their presence is in the concentration of nano or micro molecules. These molecules have different biological properties from native ones and are distributed differently in different tissues and cells.

In addition, in the in-vitro studies native polyphenol molecules have been used at high concentrations, or above physiological (over 100 micromoles).

This is the first reason why a clinical trial case study was planned. Polyphenols also modulate cell membranes, enzymes, transcription factors and receptors. This is the second reason why nutrigenomics will be studied during the course of the clinical trial to evaluate the effects of polyphenols on the molecular and cellular mechanisms of the inflammatory processes that are present in the ulcerative colitis.

In vivo experiments demonstrated that the administration of a diet associated with daily intake of EVOO reduces histological lesions and symptomatology in rats with a DDS induced colitis. A diet supplemented with hydroxytyrosol (a component of olive oil) showed a reduction of the inflammatory process at the inflamed colon of the rats.

These data show that EVOO supplementation in a diet can improve the course of the disease.

Experimental studies in humans are limited. The first study published over 25 years ago concluded that administering a supplement of fish oil to the diet produced a modest reduction in corticosteroid in the active phases of the disease, but not a benefit in maintenance therapy over olive oil. This work presents important limitations:

1. the content of polyphenols in the oils used is unknown
2. the remission time between the two oils was not statistically significant
3. there are no data on inflammation of the colon before and after treatment Recently, an in vitro study performed on intestinal mucosa obtained from 14 active UC patients showed that samples treated with oleuropein had a reduced expression of two inflammatory factors, COX-2 and IL-17, suggesting that olive oil containing oleuropein can improve inflammatory status.

The aim of the study is to evaluate whether MC- EVOO supplementation in moderate to severe UC patients needing a steroid cycle may increase the clinical response rate to medical therapy.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Pilot study
• Masking: Double (Participant, Investigator)
• Masking Description: Patients will receive a bottle with experiental oil or placebo, consisting of commercial refined olive oil. No diffencences between the two bottles.
• Primary Purpose: Supportive Care
• Official Title: Supplementation of Extra Virgin Olive Oil Monocultivar Coratina in Patients With Active Ulcerative Colitis
• Actual Study Start Date: November 20, 2017
• Estimated Primary Completion Date: December 1, 2018
• Estimated Study Completion Date: December 31, 2019

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: MC-EVOO in addition to steroid therapy; Oral beclomethasone dipropionate at dose of 10 mg / day for the first 4 weeks, 5 mg / day for the second 4 weeks plus MC- EVOO for 12 weeks at a dose of 2 tablespoons per day (1 before lunch and 1 before dinner). Each spoon will contain 10 grams of oil containing 5 mg of biophenols.	Combination Product: Beclomethasone dipropionate in addition to MC-EVOO; Oral beclomethasone dipropionate at dose of 10 mg / day for the first 4 weeks, 5 mg / day for the second 4 weeks plus MC- EVOO for 12 weeks at a dose of 2 tablespoons per day (1 before lunch and 1 before dinner). Each spoon will contain 10 grams of oil containing 5 mg of biophenols.
Placebo Comparator: Refined olive oil and steroid therapy; Oral beclomethasone dipropionate (10 mg / day for the first 4 weeks, 5 mg / day for the second 4 weeks) plus placebo consisting of refined olive oil with low biophenols.	Combination Product: Beclomethasone dipropionate in addition to refined oil; Oral beclomethasone dipropionate (10 mg / day for the first 4 weeks, 5 mg / day for the second 4 weeks) plus placebo consisting of refined olive oil with low biophenols.

Outcome Measures

Primary Outcome Measures :

1. Evaluation of the short-term clinical response [ Time Frame: 12 weeks ]
   Evaluation of the short-term clinical response rate in the 2 treatment groups

Secondary Outcome Measures :

1. Evaluation of the clinical remission [ Time Frame: 12 weeks ]
   Evaluation of the clinical remission rate in the short term in the 2 treatment groups
2. Evaluation of the endoscopic remission [ Time Frame: 12 weeks ]
   Evaluation of the endoscopic remission rate after 3 months in the 2 treatment groups
3. Evaluation of markers of inflammation [ Time Frame: 12 weeks ]
   Evaluation of the rate of patients with normalization of markers of inflammation in the short and medium term in the 2 treatment groups
4. Evaluation of adverse events [ Time Frame: 12 weeks ]
   Evaluation of the rate of adverse events in the 2 treatment groups

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patients with active UC (diagnosed for at least 3 months) aged 18 to 70 years
• Patients with mild to moderate disease (calculated by Mayo score).
• Patients can provide their informed consent to participate in the study

Exclusion Criteria:

• Patients with Crohn's disease
• Patients with complicated disease, who are candidates for urgent surgery
• Patients with colostomy
• Patients with contraindications to steroid therapy (diabetes mellitus, severe osteoporosis, vertebral fractures, previous intolerance to steroid therapy)
• Patients with unstable or inappropriately controlled cardiovascular, pulmonary, hepatic, renal or hematologic diseases
• Patients who are not compliant
• Patients abusing alcohol or drugs

Contacts and Locations

Contacts

Contact: Fabrizio Bossa, MD; +39 0882416281; f.bossa@operapadrepio.it

Locations

Italy

IRCCS Casa Sollievo della Sofferenza; Recruiting

San Giovanni Rotondo, Foggia, Italy, 71013

Contact: Angelo Andriulli, MD 0039 0882 410263 a.andriulli@operapadrepio.it

Contact: Orazio Palmieri, BSc 0039 0882416281 o.palmieri@operapadrepio.it

Sponsors and Collaborators

Casa Sollievo della Sofferenza IRCCS

Fondazione Schena

More Information

Publications:

Danese S, Fiocchi C. Ulcerative colitis. N Engl J Med. 2011 Nov 3;365(18):1713-25. doi: 10.1056/NEJMra1102942. Review.

Ng SC, Bernstein CN, Vatn MH, Lakatos PL, Loftus EV Jr, Tysk C, O'Morain C, Moum B, Colombel JF; Epidemiology and Natural History Task Force of the International Organization of Inflammatory Bowel Disease (IOIBD). Geographical variability and environmental risk factors in inflammatory bowel disease. Gut. 2013 Apr;62(4):630-49. doi: 10.1136/gutjnl-2012-303661. Epub 2013 Jan 18. Review.

Koloski NA, Bret L, Radford-Smith G. Hygiene hypothesis in inflammatory bowel disease: a critical review of the literature. World J Gastroenterol. 2008 Jan 14;14(2):165-73. Review.

Sánchez-Fidalgo S, Sánchez de Ibargüen L, Cárdeno A, Alarcón de la Lastra C. Influence of extra virgin olive oil diet enriched with hydroxytyrosol in a chronic DSS colitis model. Eur J Nutr. 2012 Jun;51(4):497-506. doi: 10.1007/s00394-011-0235-y. Epub 2011 Aug 27.

Takashima T, Sakata Y, Iwakiri R, Shiraishi R, Oda Y, Inoue N, Nakayama A, Toda S, Fujimoto K. Feeding with olive oil attenuates inflammation in dextran sulfate sodium-induced colitis in rat. J Nutr Biochem. 2014 Feb;25(2):186-92. doi: 10.1016/j.jnutbio.2013.10.005. Epub 2013 Nov 8.

Reddy KVK, Naidu KA. Oleic acid, hydroxytyrosol and n-3 fatty acids collectively modulate colitis through reduction of oxidative stress and IL-8 synthesis; in vitro and in vivo studies. Int Immunopharmacol. 2016 Jun;35:29-42. doi: 10.1016/j.intimp.2016.03.019. Epub 2016 Mar 24.

Hawthorne AB, Daneshmend TK, Hawkey CJ, Belluzzi A, Everitt SJ, Holmes GK, Malkinson C, Shaheen MZ, Willars JE. Treatment of ulcerative colitis with fish oil supplementation: a prospective 12 month randomised controlled trial. Gut. 1992 Jul;33(7):922-8.

Larussa T, Oliverio M, Suraci E, Greco M, Placida R, Gervasi S, Marasco R, Imeneo M, Paolino D, Tucci L, Gulletta E, Fresta M, Procopio A, Luzza F. Oleuropein Decreases Cyclooxygenase-2 and Interleukin-17 Expression and Attenuates Inflammatory Damage in Colonic Samples from Ulcerative Colitis Patients. Nutrients. 2017 Apr 15;9(4). pii: E391. doi: 10.3390/nu9040391.

• Responsible Party: Angelo Andriulli, Medical Doctor, Casa Sollievo della Sofferenza IRCCS
• ClinicalTrials.gov Identifier: NCT03408847
• Other Study ID Numbers: EVO-RCU-2017
• First Posted: January 24, 2018
• Last Update Posted: February 7, 2018
• Last Verified: February 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Angelo Andriulli, Casa Sollievo della Sofferenza IRCCS:

Ulcerative colitis; UC; Extra virgin olive oil; Polyphenols

Additional relevant MeSH terms:

Colitis; Colitis, Ulcerative; Ulcer; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases; Pathologic Processes; Inflammatory Bowel Diseases; Beclomethasone; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents