Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000150145
Ethics application status
Approved
Date submitted
24/01/2019
Date registered
1/02/2019
Date last updated
29/04/2019
Date data sharing statement initially provided
1/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
COLONiC: Consequences of OLive Oil replacemenNt on ulcerative Colitis
Scientific title
Influence of Extra Virgin Olive Oil intake on Disease Activity and Gut Microbiota Profile of Community Dwelling Adults with Ulcerative Colitis in Comparison to Healthy Subjects
Secondary ID [1] 295027 0
None
Universal Trial Number (UTN)
U1111-1214-7786
Trial acronym
COLONiC: Consequences of OLive Oil replacemenNt on ulcerative Colitis
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ulcerative Colitis
 308044 0
Condition category
Condition code
Oral and Gastrointestinal 307095 307095 0 0
Inflammatory bowel disease
Inflammatory and Immune System 307096 307096 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The COLONIC Study aims to investigate the impact of replacing a portion of dietary fats with extra virgin olive oil (EVOO) in the diet of community dwelling healthy subjects in comparison to those living with Ulcerative Colitis.

For both subject groups (those with UC and those without IBD), we will randomize participants into 1 of 2 diet groups; 1) total replacement of all free dietary fats with EVOO and 2) usual care, no dietary replacement. As such; participant groups would be divided into 4 groups:
1) Participants with UC - intervention (replace all free fats with EVOO)
2) Participants with UC - usual care
3) Participants without UC - intervention (replace all free fats with EVOO)
4) Participants without UC - usual care

Free dietary fats will be defined as fats added into home made meal preparations. Examples of this includes but is not limited to cooking oil, butter, fat based spreads (e.g., margarine), and oils added into sauces and/or dressings. Fats which are an inseparable component to a food product (e.g., fat in milk, cheese, meats, nuts) will not be included in the amount calculated to be replaced. Similarly, meals not prepared at home such as restaurant foods, commercial baked goods and meals prepared by other individuals will not be included in the calculation.

Calculation of the replacement will be obtained from three day weighted food diaries to be completed by all participants at baseline. The free fats from these diaries will be identified, and the research team will calculate the average daily energy contribution in kJ provided by these food items. The dose of EVOO provided for each participant on a daily basis will be based on the average daily energy contribution of their free fat intake. We will use both nutrition reference databases (AUSNUT2011-13) and EVOO manufacturer's nutrition information as a reference point for the conversion of calories contributed by EVOO into grams.

The EVOO used for this study will be a commercially available product in accordance with Food Standards Australia New Zealand (FSANZ) regulations, and not a specially prepared product. Participants will be provided with the replacement EVOO by the research team for home use and will be instructed to only use the replacement oil during the intervention phase.

We will aim for participant to use the replacement oil daily over a four week intervention period. All other aspects of the diet will need to be maintained during the study period. Participants will also be requested to maintain all other lifestyle factors including physical activity, intake of food supplements and any medication or therapies. In the event that any changes occur during the study period, this will be captured during a weekly follow up session over the phone.

To ensure adherence during the intervention, a session with the study dietitian will be organized prior to commencement of the intervention and at 2 weeks post intervention. The session will focus on coaching, strategies to replace the free fats with the study oil, and identify practical areas where the study fat can be incorporated. Support will be provided in the form of weekly teleconferences and a fortnight face to face session. A study log will also be provided to allow for daily logging of the study oil consumption, identify areas of concern, and record any new clinical symptoms. Pre-filled and measured bottles of EVOO will also be provided to ensure accurate daily dosing during the study period.

At the end of the four week intervention, participants will complete an in person assessment at the University of Sydney which will include physical assessments, collection of biospecimens (blood, stool), and completion of a 3 day weighted food diary. After completion of this mid-point assessment, all the EVOO bottles including any unused batches will be collected from the participant's household.

At this point participants in the intervention group will undergo a four week washout period. Participants will be requested to resume using their preferred oil and fats for daily use as outlined in their 3 day weighted food diary at baseline. Participants will also be instructed to maintain usual intake and avoid changing their dietary patterns during this time period. The researchers will also have information of the usual diet collected at baseline prior to intervention as a general reference. Weekly teleconferences with the participants will continue during the washout period to identify any changes to behavior or medical therapy.
Intervention code [1] 301357 0
Lifestyle
Intervention code [2] 301358 0
Behaviour
Intervention code [3] 301359 0
Treatment: Other
Comparator / control treatment
Participants will receive usual care as documented at baseline. Participants will be requested to continue with their current lifestyle (diet and physical activity levels) over an 8 week period. Any changes to the medical therapy received by the participant including new treatments, surgery, and other pharmacological or non-pharmacological interventions to improve IBD symptoms and quality of life will be recorded (e.g. counselling, Cognitive Behaviour Therapy, mindfulness, massage therapy). Participants will have the opportunity to report these changes during a weekly teleconference.
Control group
Active

Outcomes
Primary outcome [1] 306076 0
Ulcerative Colitis disease activity as determined via the partial Mayo scoring Index
Timepoint [1] 306076 0
Weekly from baseline to 8 weeks
Primary outcome [2] 306209 0
Gut microbiota variety and richness via faecal samples (composite outcome based on gut bacteria profiles)
Timepoint [2] 306209 0
Baseline, 4 weeks, 8 weeks
Secondary outcome [1] 347486 0
Diet quality (including energy intake, macronutrient profile) and variety of the 3 day weighted food record submitted and Food Frequency Questionnaire (FFQ)
Timepoint [1] 347486 0
Baseline, 4 weeks and 8 weeks
Secondary outcome [2] 347824 0
Malnutrition risk via the Mini Nutritional Assessment (MNA)
Timepoint [2] 347824 0
Baseline, 4 weeks, and 8 weeks
Secondary outcome [3] 347825 0
Food Frequency Questionnaire (FFQ) over a 1 month period
Timepoint [3] 347825 0
Baseline, 4 weeks and 8 weeks
Secondary outcome [4] 347826 0
Participant's current intake of medications (including probiotics and nutraceuticals). via a questionnaire specifically developed for this study
Timepoint [4] 347826 0
Baseline and revisited in weekly status checks for any changes
Secondary outcome [5] 347829 0
Fatty acid profile of the 3 day food diary as determined by FoodWorks
Timepoint [5] 347829 0
Baseline, 4 weeks, and 8 weeks
Secondary outcome [6] 347830 0
Polyphenol content of the reported diet (via 3-day food diary) as determined by FoodWorks
Timepoint [6] 347830 0
Baseline, 4 weeks, 8 weeks
Secondary outcome [7] 347831 0
Diet Inflammatory Index (DII) of participant's 3 day food diary
Timepoint [7] 347831 0
Baseline, 4 weeks, 8 weeks
Secondary outcome [8] 347832 0
Plasma Oleic Acid levels
Timepoint [8] 347832 0
Baseline, 4 weeks, 8 weeks
Secondary outcome [9] 347833 0
Faecal Short Chain Fatty Acid (SCFA) content
Timepoint [9] 347833 0
Baseline, 4 weeks, 8 weeks
Secondary outcome [10] 347834 0
Plasma Hydroxityrosol sulfate via gas chromatography–mass spectrometry (GC–MS)
Timepoint [10] 347834 0
Baseline, 4 weeks, 8 weeks
Secondary outcome [11] 347835 0
Self-reported symptoms via the weekly status check

Participants will be queried on symptoms experienced (e.g. pain, bloody diarrhea, loose stools) and and outline if any known "trigger" foods was consumed prior.
Timepoint [11] 347835 0
Baseline and revisited in weekly status checks for any changes
Secondary outcome [12] 347842 0
Bone density in the lumbar spine and hip via Dual-energy X-ray absorptiometry (DXA)
Timepoint [12] 347842 0
Baseline, 4 weeks, 8 weeks
Secondary outcome [13] 347843 0
Serum levels of Tumour Necrosis Factor Alpha via ELISA
Timepoint [13] 347843 0
Baseline, 4 weeks, 8 weeks
Secondary outcome [14] 347844 0
Blood C-Reactive Protein via C-reactive protein (CRP) test
Timepoint [14] 347844 0
Baseline, 4 weeks, 8 weeks
Secondary outcome [15] 347845 0
Erythrocyte Sedimentation Rate (ESR) via sedimentation rate test of whole blood samples
Timepoint [15] 347845 0
Baseline, 4 weeks, 8 weeks
Secondary outcome [16] 347849 0
Faecal IgA via enzyme-linked immunosorbent assays (ELISA)
Timepoint [16] 347849 0
Baseline, 4 weeks, 8 weeks
Secondary outcome [17] 347852 0
Blood Lipopolysaccharides (LPS)
Timepoint [17] 347852 0
Baseline, 4 weeks, 8 weeks
Secondary outcome [18] 347853 0
Serum levels of Folate
Timepoint [18] 347853 0
Baseline, 4 weeks, 8 weeks
Secondary outcome [19] 347854 0
Serum levels of Calcium
Timepoint [19] 347854 0
Baseline, 4 weeks, 8 weeks
Secondary outcome [20] 347855 0
Serum levels of vitamin D
Timepoint [20] 347855 0
Baseline, 4 weeks, 8 weeks
Secondary outcome [21] 347858 0
Inflammatory Bowel Disease (IBD) Questionnaire
Timepoint [21] 347858 0
Baseline, 4 weeks, 8 weeks
Secondary outcome [22] 347859 0
Depressive Symptoms via patient health questionnaire (PHQ-9)
Timepoint [22] 347859 0
Baseline, 4 weeks, 8 weeks
Secondary outcome [23] 347860 0
Hospital and Anxiety Depression Index (HADS)
Timepoint [23] 347860 0
Baseline, 4 weeks, 8 weeks
Secondary outcome [24] 347861 0
Quality of life via the SF-36® Health Survey
Timepoint [24] 347861 0
Baseline, 4 weeks, 8 weeks
Secondary outcome [25] 347862 0
Fatigue via the Inflammatory Bowel Disease (IBD) Fatigue Scale
Timepoint [25] 347862 0
Baseline, 4 weeks, 8 weeks
Secondary outcome [26] 347865 0
7-day physical activtiy via an Axivity MEMS 3-axis accelerometer
Timepoint [26] 347865 0
Baseline, 4 weeks, 8 weeks
Secondary outcome [27] 347868 0
Participant reported adverse events (e.g. accident, misadventure unrelated to the study, UC flare) via the weekly status check form developed for this study
Timepoint [27] 347868 0
Weekly from baseline to 8 weeks
Secondary outcome [28] 366229 0
Plasma Tyrosol via gas chromatography–mass spectrometry (GC–MS)
Timepoint [28] 366229 0
Baseline, 4 weeks, and 8 weeks
Secondary outcome [29] 366233 0
IgA coating bacteria in stool analysis via 16S rRNA sequencing
Timepoint [29] 366233 0
Baseline, 4 weeks, 8 weeks
Secondary outcome [30] 366234 0
Fecal levels of Interleukin 1 (IL1) via ELISA
Timepoint [30] 366234 0
Baseline, 4 weeks, 8 weeks
Secondary outcome [31] 366235 0
Fecal levels of Interleukin 6 (IL6) via ELISA
Timepoint [31] 366235 0
Baseline, 4 weeks, 8 weeks
Secondary outcome [32] 366236 0
Fecal levels of Interleukin 10 (IL10) via ELISA
Timepoint [32] 366236 0
Baseline, 4 weeks, 8 weeks
Secondary outcome [33] 366237 0
Fecal levels of Interleukin 12 (IL12) via ELISA
Timepoint [33] 366237 0
Baseline, 4 weeks, 8 weeks
Secondary outcome [34] 366244 0
Fecal LPS via Pro Q Emerald 300 Gel Staining kit (Thermo Fisher Scientific)
Timepoint [34] 366244 0
Baseline, 4 weeks, 8 weeks
Secondary outcome [35] 369787 0
Food related quality of life via the FR-QoL-29
Timepoint [35] 369787 0
Baseline, Week 4, Week 8

Eligibility
Key inclusion criteria
For Individuals with Ulcerative Colitis:
1) Aged >= 18 at the time of recruitment
2) Ulcerative colitis (UC) >3 months duration of any extent .
3) Willingness to participate in the study protocol, randomization and provide informed consent

For non-IBD subjects:
1) Aged >= 18 years at the time of recruitment
2.) Willing to be randomized into one of the two study arms and participate in the intervention prescribed
3) Stable medication. All drugs to be held at constant dose during the study and no changes to medication in the preceding 4 weeks.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
For individuals with Ulcerative Colitis (UC)
1) Currently living with other Inflammatory Bowel Disease not defined as UC (e.g. Crohn's disease, non specific IBD)
2) History of fecal microbiota transplantation
3) Significant prior gastrointestinal surgery (e.g., colon resection, colectomy) or clinical evidence of any comorbid chronic disease that may interfere with the patient’s ability to enter the trial and undertake the testing
4) Planned major surgery within the first 3 months after randomization
5) Antibiotic/anti-tuberculosis treatment for any reason during the study period or in the preceding 4 weeks
6) Changes to UC medical therapy within 4 weeks of study initiation
7) Pregnant or female planning pregnancy for the first 3 months post randomisation
8) Diagnosed allergy or intolerance towards olives or olive based products, or avoidance of olive based products for any other reason
9) Daily consumption of olives or olive based products including spreads, oils, marinated olives, tapenade, or supplements such as olive leaf extract
10) Those undertaking a specialized diet in which the intervention would be deemed inappropriate (e;g;, fat reduction or low fat diet) or those whose diet is currently under the supervision of a relevant medical professional
11) Medical nutrition therapy under supervision of a healthcare professional (e.g., texture modifciation, progression to a full diet post hospitaliation, FODMAP or RPA elimination diet challenge phase)
12) Use of tube or enteral feeding, elemental diet, or parenteral nutrition within 4 weeks of study initiation.
13) Regular consumption of takeaway or restaurant meals more than 3 days a week or 9 meals a week..
14) Participation in another clinical trial for with concurrent participation is deemed inappropriate.

For participants in the non-IBD group:
1) History of Inflammatory Bowel Disease of any description (including remission)
2) History of fecal microbiota transplantation
3) Significant prior gastrointestinal surgery (e.g., colon resection, colectomy) or clinical evidence of any comorbid chronic disease that may interfere with the patient’s ability to enter the trial and undertake the testing
4) Planned major surgery within the first 3 months after randomization
5) Antibiotic/anti-tuberculosis treatment for any reason during the study period or in the preceding 4 weeks
6) Changes to UC medical therapy within 4 weeks of study initiation
7) Pregnant or female planning pregnancy for the first 3 months post randomisation
8) Diagnosed allergy or intolerance towards olives or olive based products, or avoidance of olive based products for any other reason
9) Daily consumption of olives or olive based products including spreads, oils, marinated olives, tapenade, or supplements such as olive leaf extract
10) Those undertaking a specialized diet in which the intervention would be deemed inappropriate (e;g;, fat reduction or low fat diet) or those whose diet is currently under the supervision of a relevant medical professional
11) Medical nutrition therapy under supervision of a healthcare professional (e.g., texture modifciation, progression to a full diet post hospitaliation, FODMAP or RPA elimination diet challenge phase)
12) Use of tube or enteral feeding, elemental diet, or parenteral nutrition within 4 weeks of study initiation.
13) Regular consumption of takeaway or restaurant meals more than 3 days a week or 9 meals a week..
14) Participation in another clinical trial for with concurrent participation is deemed inappropriate.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation will be concealed using sealed opaque envelopes given to eligible participants after completion of all baseline testing. There are 4 groups in total, which comprise of 2 study groups (Individuals with UC and non-IBD participants) subjected to randomization into 2 diet groups (usual care group and fat replacement group) following completion of baseline assessments.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will involve a concealed, computer-generated sequence of randomly permuted variable blocks of four, stratified for concomitant corticosteroid use. The randomisation sequence will be generated by an online program created by a statistician not otherwise involved in the study.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Intention-to-treat analysis regardless of dropout or study adherence; Primary and secondary continuous outcomes analyzed via linear repeated measures mixed models for testing of Group X Time interaction, with covariate adjustment over the intervention duration. Categorical outcomes analyzed as Risk Ratios and logistic regression models adjusted for covariates will be calculated. Covariates selected a priori include age, sex, appendicular skeletal muscle mass, macronutrient, energy and probiotic intake, habitual physical activity level; other potential confounders identified at baseline may be added. Mediation analysis will be conducted via the PROCESS macro for SPSS version 2.13.2 will be used to determine the indirect effect of the diet on objective and subjective responses mediated by hypothesised beneficial alterations in the gut biome, while accounting for any direct effects of diet change.

Power Calculations:
At the time of writing, there were limited published papers identifying the effects of diet on active Ulcerative Colitis. We identified three studies on dietary intervention; 1 randomized controlled trial of a single food component (2) and two uncontrolled trials of a comprehensive diet intervention (2, 3). Only the two uncontrolled studies had enough information to allow for the calculation of an effect size. Hedges’ bias corrected effect sizes were calculated from published means and standard deviations of a single group, pre-post study involving a dietary intervention over 8 weeks (2) and 6 weeks (3)

The effect size of a dietary intervention in active Ulcerative Colitis calculated from these studies were 0.917 (2) and 2.638 (3) respectively. With consideration to the current study design which includes adult populations and the use of the same scoring tool, we have selected the paper by Konijeti, et. al (3) to estimate sample size.

Based on the available evidence, we hypothesize that EVOO consumption would elicit a similar reduction to average Mayo Score in the intervention group compared to those randomized into the usual care group. Due to the single dietary intervention used in this study and accounting for the uncontrolled study cited, a conservative approach to estimate effect size was implemented.

We calculated effect size based on a 2 point (22%) reduction in the Partial Mayo Score (less than half of the mean difference cited in literature), with alpha 0.05 and beta 0.8. Effect size was calculated to be 1.25, with a sample size of 12 participants per group (24 individuals with Ulcerative Colitis randomized to either the intervention or usual care) required to determine changes in disease activity post intervention. Accounting for a 16% dropout rate which occurred in both studies selected, we will aim to recruit 28 participants with Ulcerative Colitis.

With consideration to those without a history of Inflammatory Bowel Disease, we will also aim to recruit an equal number of participants. Due to the limited evidence available on the effects of EVOO consumption on the gut microbiome and inflammatory markers in apparently healthy individuals, the recruitment number of apparently healthy controls are not based on any hypotheses on the differences between those living with UC and non-IBD cohorts subjected to EVOO consumption or dietary intervention. In total, we will aim to recruit 56 participants for this study; 28 individuals with UC and 28 individuals without a history of IBD.

References:
1. Kanauchi O, Suga T, Tochihara M, Hibi T, Naganuma M, Homma T, et al. Treatment of ulcerative colitis by feeding with germinated barley foodstuff: first report of a multicenter open control trial. J Gastroenterol. 2002;37 Suppl 14:67-72.
2. Suskind DL, Cohen SA, Brittnacher MJ, Wahbeh G, Lee D, Shaffer ML, et al. Clinical and Fecal Microbial Changes With Diet Therapy in Active Inflammatory Bowel Disease. J Clin Gastroenterol. 2016.
3. Konijeti GG, Sanchez C, Caroline D, Singh E, Lewis JD, Kim N, et al. Efficacy and tolerability of the autoimmune protocol diet for inflammatory bowel disease. Gastroenterology. 2017;152 (5 Supplement 1):S401-S2.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
30/04/2019
Actual
Date of last participant enrolment
Anticipated
6/01/2020
Actual
Date of last data collection
Anticipated
30/04/2020
Actual
Sample size
Target
56
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 299607 0
University
Name [1] 299607 0
The University of Sydney
Country [1] 299607 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
Faculty of Health Sciences
75 East St,
Lidcombe NSW 2141
Country
Australia
Secondary sponsor category [1] 298928 0
None
Name [1] 298928 0
Address [1] 298928 0
Country [1] 298928 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300510 0
The University of Sydney Human Research Ethics Committee
Ethics committee address [1] 300510 0
Margaret Telfer Building (K07)
University of Sydney NSW 2006
Ethics committee country [1] 300510 0
Australia
Date submitted for ethics approval [1] 300510 0
29/06/2018
Approval date [1] 300510 0
24/04/2019
Ethics approval number [1] 300510 0

Summary
Brief summary
Ulcerative Colitis (UC) is an inflammatory bowel disease (IBD) mainly affecting the lining of the large intestine (colon) and rectum. It is a chronic, progressive condition characterised by periods of acute inflammation and remission. Symptoms may include abdominal pain, bloating, fatigue, frequency, urgency, and bloody stools. Although treatment options have improved in recent years, there exist a need for non-pharmacological options to support medical therapy and improve outcomes. Recent studies demonstrate the positive effects of extra virgin olive oil supplementation in animal models, and it is associated with prevention of the disease in Mediterrannean populations.. Separate lines of research has further demonstrated potential anti inflammatory properties of olive oil in the diet for other chronic inflammatory processes. .
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 83890 0
Prof Maria A. Fiatarone Singh, MD, FRACP
Address 83890 0
University of Sydney Cumberland Campus
Building K, Room K221
75 East Street,
Lidcombe, 2141 NSW
Australia
Country 83890 0
Australia
Phone 83890 0
+61 2 9351 9755
Fax 83890 0
+61 2 9351-9204
Email 83890 0
[email protected]
Contact person for public queries
Name 83891 0
Mr Kenneth Daniel
Address 83891 0
University of Sydney Cumberland Campus
Building K, Room K220
75 East Street,
Lidcombe, 2141 NSW
Australia
Country 83891 0
Australia
Phone 83891 0
+61 2 9351-9138
Fax 83891 0
+61 2 9351-9204
Email 83891 0
[email protected]
Contact person for scientific queries
Name 83892 0
Prof Maria A. Fiatarone Singh, MD, FRACP
Address 83892 0
University of Sydney Cumberland Campus
Building K, Room K221
75 East Street,
Lidcombe, 2141 NSW
Australia
Country 83892 0
Australia
Phone 83892 0
+61 2 9351 9755
Fax 83892 0
+61 2 9351-9204
Email 83892 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
All data collected from this study will be presented in aggregate form for the purposes of publication and dissemination. In the event that individual data is selected to be presented (e.g. outliers, specific case studies), steps will be taken to ensure that participant's privacy is ensured (e.g. using labels or study codes) in line with the study's Research Data Management Plan (RDMP) and HREC requirements.


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Results publications and other study-related documents

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