Clinical trial NCT02796339: A Study on the Effectiveness of a Nutritional Supplement With Natural Mastiha in Inflammatory Bowel Diseases.
Official title: A Phase-II Clinical Trial on the Effectiveness of a Nutritional Supplement With Natural Mastiha in Inflammatory Bowel Diseases Patients.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Inflammatory Bowel Diseases
Keywords: Inflammatory Bowel Diseases
natural Mastiha
supplement
Lead sponsor: Harokopio University
Sponsor class: OTHER
First posted: 2016-06-10
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 67
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: The purpose of this study is to assess the effectiveness of a supplement with natural Mastiha on Inflammatory Bowel Diseases (IBD). U.S. Food and Drug Administration has classified Mastiha as GRAS. Previous research demonstrates Mastiha's safety, as well as anti-inflammatory, antimicrobial and antioxidant properties. In addition, the European Medicine Agency has recently recognized Mastiha as a natural medicine and classified it to the category of traditional herbal medicines in diarrhea problems, mild dyspeptic disorders, skin inflammation and healing (EMA/HMPC/46758/2015). Since IBD is a chronic disease characterized by inflammation and oxidative stress and based on previous small-scale studies, the present study aims at demonstrating the effectiveness of this supplement adjunct to the conservative treatment of IBD.

To this end, confirmed IBD patients, with distinguished Ulcerative Colitis (UC) and Crohn's Disease (CD) will be enrolled based on certain inclusion and exclusion criteria. The staff of the study will provide detailed information regarding the aims, the methods, anticipated benefits and potential hazards of the study and all patients will receive the Patient Information Leaflet (PIL). Ample time (48 hours) will be provided in order to decide whether they want to participate in the protocol. Each patient agreeing to participate will sign an Informed Consent document and the staff will explain to patients that they are under no obligation to enter the trial and that they can withdraw at any time during the trial, without having to give a reason. A copy of the signed Informed Consent will be given to the participant.

100 IBD patients will be allocated to either Mastiha or placebo group. The Mastiha group will receive natural Mastiha supplement at a dose of 2.8 g daily while placebo group will receive respectively placebo. The intervention will last 3 months for patients in relapse and 6 months for patients in remission. They will receive all the supplements they will consume during the intervention at the start of the trial. Both groups will continue their medical treatment, which must be unaltered throughout the trial. Additionally, all patients will receive standard nutritional advice by dieticians and will be encouraged to report any adverse effects they may experience during the intervention. The trial will be blinded in all implicated persons; neither the staff of the trial nor the patients will be aware of which kind intervention they receive.

Patients are assessed after randomisation according to the following tools:

* Medical history
* Dietary history
* Harvey \& Bradshaw Activity Index Assessment
* Mayo Activity Index assessment
* Anthropometric data measurement: body weight (kg), height (cm), Body Mass Index (kg/m2)
* Inflammatory Bowel Disease Questionnaire
* DNA isolation from whole blood.
* Biochemical measurements: Complete blood count, albumin, lipid profile, glucose, electrolytes, liver enzymes, amylase, fibrinogen.
* Evaluation of inflammation in serum samples. Circulating serum levels of IL-6, IL-8, IL-17A, IL-17F, IL-18, IL-21, IL-22, TL1A, TGF-β, ICAM-1, MADCAM-1 and E-selectin are measured), in all active CD and UC patients. Inflammatory markers are also estimated in stool samples: calprotectin, lactoferrin and lysozyme,
* Oxidative stress assessment in serum/plasma samples. Oxidised LDL, serum oxidisability and F2-isoprostanes are quantified.
* Detection of metabolites and complete metabolomic profile in plasma samples.
* Stool samples collection for the assessment of gut microbiota in active patients.
* Genetic and epigenetic profile

Subsequent assessments: There is a biweekly telephone contact with the patients to monitor compliance and side effects. At the end of the intervention each subject undergoes the baseline assessment.


Eligibility criteria: Eligibility criteria for patients in relapse

Inclusion criteria:

* Age 18-67 years
* Active disease, CD defined by Harvey \& Bradshaw Activity Index ≥4; UC defined by Partial Mayo Clinic Score (2\<= Mayo Scoring Index)
* Childbearing age with a negative pregnancy test at eligibility and baseline assessment
* Stable treatment with steroids for at least 2 weeks before the start of the trial, mesalamine and mesalamine analogues for 4 weeks and immunosuppressants for 8 weeks
* Stable medication during the whole period of the 3-month intervention

Exclusion criteria:

* Positive stool culture for enteric pathogens or Clostridium difficile toxin
* Antibiotic treatment during and 2 months prior to screening
* Bowel surgery ≤3 months prior to screening; a planned elective surgery or hospitalisation during the study; clinically significant short bowel syndrome; presence of an intra-abdominal abscess or a fistula with clinical or radiological evidence of an associated abscess; ileostomy; colostomy
* Enteral or parenteral nutrition; Alcohol or drug abuse,Vitamin or inorganic supplements, vegan or macrobiotic diet before and during the trial
* Any malignancy in the year prior to screening; CVD; peptic ulcer
* Pregnancy, lactation

Eligibility criteria for patients in remission

Inclusion criteria:

* Age 18-67 years
* Inactive disease (\>3 months), CD defined by Harvey \& Bradshaw (\<6 Index) and UC defined by Partial Mayo Clinic (0-1 Mayo Scoring Index)
* Biochemical remission
* Childbearing age with a negative pregnancy test at eligibility and baseline assessment
* Stable treatment with azathioprine or mesalamine and mesalamine analogues
* Stable medication during the whole period of the 6-month intervention

Exclusion criteria:

* Positive stool culture for enteric pathogens or Clostridium difficile toxin
* Antibiotic treatment during and 2 months prior to screening
* Bowel surgery ≤3 months prior to screening; a planned elective surgery or hospitalisation during the study; clinically significant short bowel syndrome; presence of an intra-abdominal abscess or a fistula with clinical or radiological evidence of an associated abscess; ileostomy; colostomy
* Enteral or parenteral nutrition; Alcohol or drug abuse
* Vitamin or inorganic supplements, vegan or macrobiotic diet before and during the trial
* Any malignancy in the year prior to screening; CVD; peptic ulcer
* Pregnancy, lactation

Primary outcomes:
measure: Inflammatory Bowel Disease Questionnaire (IBDQ)
timeFrame: Change in IBDQ will be assessed at 3 months from baseline in active IBD patients and at 6 months in inactive IBD patients. Data will be presented through study completion, an average of 1 year.
Secondary outcomes:
measure: Objective symptoms questionnaire (rectal bleeding and stool frequency, visible blood in faeces and urgency).
timeFrame: Change in objective symptoms will be assessed at 3 months from baseline in active IBD patients and at 6 months in inactive IBD patients. Data will be presented through study completion, an average of 1 year.
measure: C-reactive protein (CRP)
timeFrame: Change in CRP will be assessed at 3 months from baseline in active IBD patients and at 6 months in inactive IBD patients. Data will be presented through study completion, an average of 1 year.
measure: Lab inflammatory biomarkers through sandwich Elisa assays.
timeFrame: Change in lab inflammatory biomarkers will be assessed at 3 months from baseline in active IBD patients and at 6 months in inactive IBD patients. Data will be presented through study completion, an average of 1 year.
measure: Subjective symptoms questionnaire (physician rating of disease activity)
timeFrame: Change in subjective symptoms will be assessed at 3 months from baseline in active IBD patients and at 6 months in inactive IBD patients. Data will be presented through study completion, an average of 1 year.
Other outcomes:
Locations:
city: Athens
country: Greece
facility: Harokopio University
Study officials:
affiliation: ASS.PROFESSOR
name: ANDRIANA KALIORA, AS.PROFESSOR
role: PRINCIPAL_INVESTIGATOR
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