Investigation of the Effects of Curcumin and Resveratrol Supplements Added to the Mediterranean Diet on Disease Severity and Inflammatory Biomarkers in Patients With Ulcerative Colitis

Ulcerative Colitis Clinical Trial

Official title:

Investigation of the Effects of Curcumin and Resveratrol Supplements Added to the Mediterranean Diet on Disease Severity and Inflammatory Biomarkers in Patients With Ulcerative Colitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05761327
• Other study ID #: 2021/24
• Status: Completed
• Phase: N/A
• Start date: June 3, 2022
• Est. completion date: March 22, 2024

Study information

• Verified date: March 2024
• Source: Ardahan University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of the study was to examine and compare the effects of Mediterranean diet, curcumin supplementation with Mediterranean diet in individuals with ulcerative colitis, and resveratrol supplementation with Mediterranean diet in individuals with ulcerative colitis, on disease symptoms, quality of life, and inflammatory biomarkers.

Description:

In the light of the information in the literature, it is seen that the level of evidence in the existing literature is insufficient with the data obtained in terms of dietary approaches and nutritional supplements to be applied to individuals with Ulcerative Colitis (UC). In addition, when the literature was examined, no randomized controlled study was found that specifically examined the effects of the Mediterranean diet and nutritional supplements combined with diet in individuals with UC, and also compared the effects of two different nutritional supplements applied in combination with diet. In this direction, the aims of this research are;

• Mediterranean diet in individuals with UC,

• Curcumin supplement taken together with the Mediterranean diet in individuals with UC,

• Resveratrol supplement taken with the Mediterranean diet in individuals with UC, To examine and compare their effects on disease symptoms, quality of life and inflammatory biomarkers.

Hypotheses of the Research;

H0a: Mediterranean diet has no effect on disease symptoms, quality of life an inflammatory biomarkers in individuals with UC.

H0b: Curcumin supplementation in addition to the Mediterranean diet has no effect on disease symptoms, quality of life, and inflammatory biomarkers in individuals with UC.

H0c: Resveratrol supplementation in addition to the Mediterranean diet has no effect on disease symptoms, quality of life and inflammatory biomarkers in individuals with UC.

H0d: Three approaches including Mediterranean diet, curcumin and resveratrol supplements applied in addition to diet in individuals with UC; compared to each other in terms of disease symptoms, quality of life, and inflammatory biomarkers.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: March 22, 2024
• Est. primary completion date: February 18, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Male and female patients aged >18 years,

• Those previously diagnosed with ulcerative colitis and/or newly diagnosed with clinical course, consistent histology and endoscopy by a gastroenterologist,

• Mild and Moderate activity disease was confirmed by the Truelove-Witts Severity Index,

• Using a fixed dose of 5 - aminosalicylic acid (mesalazine) and/or azathioprine,

• Who did not receive nutrition therapy in the last 3 months,

• Not using anti-inflammatory drugs and antibiotic drugs in the last 4 weeks,

• Not using curcumin and resveratrol supplements before participating in the study,

• Agreeing to participate in the study voluntarily,

Exclusion Criteria:

• Women during pregnancy or lactation

• Not meeting the inclusion criteria,

• History of chronic disease (such as diabetes), hypothyroidism and hyperthyroidism, liver, kidney and cardiovascular diseases, polycystic ovary syndrome and Cushing's syndrome,

• Taking one of the anti-inflammatory and antibiotic drugs,

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Other:
• Mediterranean Diet
In the Mediterranean diet; The frequency of consumption of foods such as olive oil, olives, nuts, fish, vegetables and fruits will be given in accordance with the Mediterranean diet pyramid. During the study, it is planned to develop new recipes suitable for the nutritional habits of the individual. The researcher will be able to reach the researcher 7/24 in case of any problem experienced by the individual, and the participant's questions will be answered. Nutrition counseling to this group will be supported by an oral explanation given by the dietitian.

Dietary Supplement:
• Curcumin Supplementation
Participants will take a daily supplement of 1600 mg of curcumin. It is planned that the participants will use 120 capsules of curcumin supplement during the research.
• Resveratrol Supplementation
Participants will take a 500mg resveratrol supplement daily. Participants are planned to use 120 capsules of resveratrol supplement during the study.

Locations

Country	Name	City	State
Turkey	Inonu University Turgut Ozal Medical Center	Malatya
Turkey	Malatya Training and Research Hospital	Malatya

Sponsors (1)

Lead Sponsor	Collaborator
Ardahan University

Country where clinical trial is conducted

Turkey, 

References & Publications (13)

Ardizzone S, Bianchi Porro G. Inflammatory bowel disease: new insights into pathogenesis and treatment. J Intern Med. 2002 Dec;252(6):475-96. doi: 10.1046/j.1365-2796.2002.01067.x. — View Citation

Bernstein CN, Eliakim A, Fedail S, Fried M, Gearry R, Goh KL, Hamid S, Khan AG, Khalif I, Ng SC, Ouyang Q, Rey JF, Sood A, Steinwurz F, Watermeyer G, LeMair A; Review Team:. World Gastroenterology Organisation Global Guidelines Inflammatory Bowel Disease: Update August 2015. J Clin Gastroenterol. 2016 Nov/Dec;50(10):803-818. doi: 10.1097/MCG.0000000000000660. No abstract available. — View Citation

Cosnes J, Gower-Rousseau C, Seksik P, Cortot A. Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology. 2011 May;140(6):1785-94. doi: 10.1053/j.gastro.2011.01.055. — View Citation

Hanai H, Iida T, Takeuchi K, Watanabe F, Maruyama Y, Andoh A, Tsujikawa T, Fujiyama Y, Mitsuyama K, Sata M, Yamada M, Iwaoka Y, Kanke K, Hiraishi H, Hirayama K, Arai H, Yoshii S, Uchijima M, Nagata T, Koide Y. Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial. Clin Gastroenterol Hepatol. 2006 Dec;4(12):1502-6. doi: 10.1016/j.cgh.2006.08.008. Epub 2006 Nov 13. — View Citation

Judge TA LG. Inflammatory Bowel Disease. In: Friedman SL MK, Grendell JH, editor. CURRENT Diagnosis&Treatment in Gastroenterology 2th ed. America: McGraw-Hill Companies; 2003.

Kothari M, Mudireddy P, Swaminath A. Patient considerations in the management of ulcerative colitis - role of vedolizumab. Ther Clin Risk Manag. 2015 Aug 19;11:1235-42. doi: 10.2147/TCRM.S65650. eCollection 2015. — View Citation

Lang A, Salomon N, Wu JC, Kopylov U, Lahat A, Har-Noy O, Ching JY, Cheong PK, Avidan B, Gamus D, Kaimakliotis I, Eliakim R, Ng SC, Ben-Horin S. Curcumin in Combination With Mesalamine Induces Remission in Patients With Mild-to-Moderate Ulcerative Colitis in a Randomized Controlled Trial. Clin Gastroenterol Hepatol. 2015 Aug;13(8):1444-9.e1. doi: 10.1016/j.cgh.2015.02.019. Epub 2015 Feb 24. — View Citation

Molodecky NA, Soon IS, Rabi DM, Ghali WA, Ferris M, Chernoff G, Benchimol EI, Panaccione R, Ghosh S, Barkema HW, Kaplan GG. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012 Jan;142(1):46-54.e42; quiz e30. doi: 10.1053/j.gastro.2011.10.001. Epub 2011 Oct 14. — View Citation

Nunes S, Danesi F, Del Rio D, Silva P. Resveratrol and inflammatory bowel disease: the evidence so far. Nutr Res Rev. 2018 Jun;31(1):85-97. doi: 10.1017/S095442241700021X. Epub 2017 Dec 1. — View Citation

Sabzevary-Ghahfarokhi M, Soltani A, Luzza F, Larussa T, Rahimian G, Shirzad H, Bagheri N. The protective effects of resveratrol on ulcerative colitis via changing the profile of Nrf2 and IL-1beta protein. Mol Biol Rep. 2020 Sep;47(9):6941-6947. doi: 10.1007/s11033-020-05753-4. Epub 2020 Sep 4. — View Citation

Sadeghi N, Mansoori A, Shayesteh A, Hashemi SJ. The effect of curcumin supplementation on clinical outcomes and inflammatory markers in patients with ulcerative colitis. Phytother Res. 2020 May;34(5):1123-1133. doi: 10.1002/ptr.6581. Epub 2019 Dec 4. — View Citation

Sands BE. From symptom to diagnosis: clinical distinctions among various forms of intestinal inflammation. Gastroenterology. 2004 May;126(6):1518-32. doi: 10.1053/j.gastro.2004.02.072. No abstract available. — View Citation

Tozun N, Atug O, Imeryuz N, Hamzaoglu HO, Tiftikci A, Parlak E, Dagli U, Ulker A, Hulagu S, Akpinar H, Tuncer C, Suleymanlar I, Ovunc O, Hilmioglu F, Aslan S, Turkdogan K, Bahcecioglu HI, Yurdaydin C; Members of the Turkish IBD Study Group. Clinical characteristics of inflammatory bowel disease in Turkey: a multicenter epidemiologic survey. J Clin Gastroenterol. 2009 Jan;43(1):51-7. doi: 10.1097/MCG.0b013e3181574636. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Inflammatory Bowel Disease Questionnaire (IBDQ)	The questionnaire consists of 32 questions and 4 subsections. These sections are; systemic symptoms (5 questions), emotional function (12 questions), social function (5 questions) and intestinal symptoms (10 questions). The questionnaire consists of a 7-point Likert scale system. For each question, 1 point indicates the highest level of exposure, and 7 indicates that there is no problem. Scores range from 32 to 224, with a higher score associated with higher quality of life. Turkish version of IBDQ will be used to assess patients' quality of life.	Change from baseline Inflammatory Bowel Disease Questionnaire total score at 8 weeks
Primary	Mediterranean Diet Assessment Tool (14-MEDAS)	The Mediterranean Diet Assessment Tool will be used to measure the adherence of the participants to the Mediterranean diet. In the 14-question scale, 1 or 0 points are taken for each question asked according to the amount of consumption and these points are added. Scores are evaluated as =5 (low ), 6-9 (moderate), and =10 (high agreement).	Change from baseline Mediterranean Diet Assessment Tool total score at 8 weeks
Secondary	36-Item Short Form Survey (SF-36)	It is the most frequently used quality of life scale in the medical field and consists of 8 sub-parameters with a total of 36 items that evaluate physical and mental health. These sub-parameters are physical function, physical role limitation, pain, general health, vitality, social function, emotional role limitation, and mental health. The scores range from 0-100, with 100 points indicating the best health condition and 0 points the worst health condition.	Change from baseline physical function, physical role limitation, pain, general health, vitality, social function, emotional role limitation, and mental health scores at 8 weeks
Secondary	Truelove-Witts Severity Index	Truelove-Witts Severity Index is a clinical classification categorizes the disease as mild, moderate, and severe, based on a combination of clinical and laboratory parameters, including bowel movements, rectal bleeding, fever, tachycardia, anemia, and increased sedimentation. The Truelove-Witts classification, using clinical symptoms, is applicable to patients with ulcerative colitis,and it is easy and reliable to use in the clinic.	Change from baseline Truelove-Witts Severity Index score at 8 weeks
Secondary	Body Mass Index	Body weight measurements and height of the volunteers will be taken with height meter and scale. All measurements will be taken in light clothing and without shoes, according to International Standards for Anthropometric Assessment (ISAK) guidelines. Body mass index (BMI) will be calculated with weight (kg) / height (m)^2 formula. Results will be interpreted as kg/m^2.	Change from baseline BMI at 8 weeks
Secondary	Waist Hip Circumference Ratio	Non-stretchable tape measure will be used for waist and hip circumference. All measurements will be taken in light clothing and without shoes, according to International Standards for Anthropometric Assessment (ISAK) guidelines. Waist hip circumference ratio will be calculated with waist circumference (cm) / hip circumference (cm).	Change from baseline Waist hip circumference ratio at 8 weeks
Secondary	Daily energy intake	Food frequency will be evaluated by The Turkish Ministry of Health version of Food Frequency Questionnaire (FFQ). FFQ is a limited check list of foods and beverages with a frequency response section for subjects to report how often each item was consumed over the last three months. Food Record (FR) will be evaluated dietary recall. The patient will be asked to note down the foods she consumes for last 3 days. The obtained data from FFQ and FR will be entered into the BeBiS 7.1 software (BeBiS Comp., Istanbul, Turkey) and the daily energy intake(kcal) will be calculated.	Change from baseline from the daily energy intake at 8 weeks
Secondary	Daily protein, fat, carbohydrate and fiber intake	Food frequency will be evaluated by The Turkish Ministry of Health version of Food Frequency Questionnaire (FFQ). FFQ is a limited check list of foods and beverages with a frequency response section for subjects to report how often each item was consumed over the last three months. Food Record (FR) will be evaluated dietary recall. The patient will be asked to note down the foods she consumes for last 3 days. The obtained data from FFQ and FR will be entered into the BeBiS 7.1 software (BeBiS Comp., Istanbul, Turkey) and the daily protein, fat, carbohydrate, fiber (gram) intake will be calculated.	Change from baseline from the daily protein, fat, carbohydrate and fiber intake at 8 weeks
Secondary	Daily vitamin and mineral intake (mg)	Food frequency will be evaluated by The Turkish Ministry of Health version of Food Frequency Questionnaire (FFQ). FFQ is a limited check list of foods and beverages with a frequency response section for subjects to report how often each item was consumed over the last three months. Food Record (FR) will be evaluated dietary recall. The patient will be asked to note down the foods she consumes for last 3 days. The obtained data from FFQ and FR will be entered into the BeBiS 7.1 software (BeBiS Comp., Istanbul, Turkey) and the daily vitamin (E, B1, B2, niacin, C) and mineral (sodium, potassium, magnesium, phosphorus, iron, zinc) (mg) intake will be calculated.	Change from baseline from the daily vitamin and mineral intake (mg) at 8 weeks
Secondary	Daily vitamin and mineral intake (mcg)	Food frequency will be evaluated by The Turkish Ministry of Health version of Food Frequency Questionnaire (FFQ). FFQ is a limited check list of foods and beverages with a frequency response section for subjects to report how often each item was consumed over the last three months. Food Record (FR) will be evaluated dietary recall. The patient will be asked to note down the foods she consumes for last 3 days. The obtained data from FFQ and FR will be entered into the BeBiS 7.1 software (BeBiS Comp., Istanbul, Turkey) and the daily vitamin (A, D, K, Folate, B12) and mineral (iodine) (mcg) intake will be calculated.	Change from baseline from the daily vitamin and mineral intake (mcg) at 8 weeks
Secondary	24 Hour Recall Physical Activity Record	Individuals who will participate in the research will be asked to record the physical activities they have done within 24 hours, in minutes, and to bring them to the week in which nutritional counseling will begin. Thus, after anthropometric measurements are made on the individuals, the resting metabolic rate (RMH) will be calculated with the Harris Benedict equation and the total energy requirements will be determined together with the physical activity coefficient found by using the 24-hour physical activity record.	Pre-intervention: Beginning of the study
Secondary	C-Reactive Protein	The blood tests were performed during routine controls. The C-Reactive Protein (mg/dL) biomarkers parameters to be examined.	Change from baseline C-Reactive Protein (mg/dL) at 8 weeks.
Secondary	Hemoglobin	The blood tests were performed during routine controls. The Hemoglobin (g/dL) to be examined.	Change from baseline hemoglobin (g/dL) at 8 weeks.
Secondary	Mean Corpuscular Hemoglobin	The blood tests were performed during routine controls. The Mean Corpuscular Hemoglobin (pg) parameter to be examined.	Change from baseline Mean Corpuscular Hemoglobin (pg) at 8 weeks.
Secondary	Mean Platelet Volume and Platelet Distribution Width (fL)	The blood tests were performed during routine controls. The blood biomarkers parameters to be examined are as follows: Mean Platelet Volume (fL) Platelet Distribution Width (fL) All blood biomarkers will be interpret separately.	Change from baseline Mean Platelet Volume and Platelet Distribution Width (fL) at 8 weeks.
Secondary	Erythrocyte Sedimentation Rate (mm/hour)	The blood tests were performed during routine controls. The blood biomarkers parameters to be examined are as follows: Erythrocyte Sedimentation Rate (mm/hour)	Change from baseline Erythrocyte Sedimentation Rate (mm/hour) at 8 weeks.
Secondary	White blood cell and Thrombocyte (10^3/uL)	The blood tests were performed during routine controls. The blood biomarkers parameters to be examined are as follows: White blood cell (10^3/uL) Thrombocyte (10^3/uL) All blood biomarkers will be interpret separately.	Change from baseline White blood cell and Thrombocyte (10^3/uL) at 8 weeks.
Secondary	Blood biomarkers (%)	The blood tests were performed during routine controls. The blood biomarkers parameters to be examined are as follows: Hematocrit (%) Pro-calcitonin (%) Lymphocyte (%) Monocyte (%) Neutrophil (%) Eosinophil (%) Basophil (%) Immune Globulin G (%) Platelet-Large cell ratio (%) Red Cell Distribution Width (%)	Change from baseline blood parameters (%) at 8 weeks.