Monocultivar Coratina Extra Virgin Olive Oil in UC Patients

Study Overview
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Brief Summary
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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.

Detailed Description
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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: high content of polyphenols 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: the content of polyphenols in the oils used is unknown the remission time between the two oils was not statistically significant 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.

Official Title
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Supplementation of Extra Virgin Olive Oil Monocultivar Coratina in Patients With Active Ulcerative Colitis

Conditions
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Ulcerative Colitis Chronic Mild

Intervention / Treatment
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* Combination Product: Beclomethasone dipropionate in addition to MC-EVOO
* Combination Product: Beclomethasone dipropionate in addition to refined oil


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Pilot study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: MC-EVOO in addition to steroid therapy<br>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<br>* 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.<br>|
| Placebo Comparator: Refined olive oil and steroid therapy<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the short-term clinical response | Evaluation of the short-term clinical response rate in the 2 treatment groups | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the clinical remission | Evaluation of the clinical remission rate in the short term in the 2 treatment groups | 12 weeks | 
| Evaluation of the endoscopic remission | Evaluation of the endoscopic remission rate after 3 months in the 2 treatment groups | 12 weeks | 
| Evaluation of markers of inflammation | Evaluation of the rate of patients with normalization of markers of inflammation in the short and medium term in the 2 treatment groups | 12 weeks | 
| Evaluation of adverse events | Evaluation of the rate of adverse events in the 2 treatment groups | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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UC, Ulcerative colitis, Extra virgin olive oil, Polyphenols