Clinical trial NCT03173144: Chronic Inflammatory Disease, Lifestyle and Treatment Response
Official title: Impact of Red and Processed Meat and Fibre Intake on Treatment Outcome Among Patients With Chronic Inflammatory Diseases: Protocol for a Prospective Cohort Study on Prognostic Factors and Personalised Medicine
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Autoimmune Diseases
Inflammatory Bowel Diseases
Crohn Disease (CD)
Colitis, Ulcerative (UC)
Arthritis, Rheumatoid (RA)
Spondylarthropathies
Arthritis, Psoriatic (PsA)
Psoriasis
Hidradenitis Suppurativa (HS)
Uveitis
Keywords: Life Style
Diet
Food
Exercise
Treatment Outcome
Biomarkers
Smoking
Lead sponsor: University of Southern Denmark
Sponsor class: OTHER
Collaborators: name: Hospital of Southern Jutland
name: University Hospital Bispebjerg and Frederiksberg
name: University of Copenhagen
name: Odense University Hospital
name: University of Aarhus
name: Aalborg University Hospital
name: Herning Hospital
name: Esbjerg Hospital - University Hospital of Southern Denmark
name: Sygehus Lillebaelt
name: Aalborg University
name: University of Kiel
name: Colitis-Crohn Foreningen
name: Herlev Hospital
name: Regionshospitalet Silkeborg
name: Aarhus University Hospital
name: The Danish Psoriasis Association
First posted: 2017-06-01
Enrollment: 233
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: targeted therapy and able to read and understand Danish.

Brief summary: Chronic inflammatory diseases (CID) - including inflammatory bowel diseases (Crohn's disease and ulcerative colitis), rheumatic conditions (rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis), inflammatory skin diseases (psoriasis, hidradenitis suppurativa) and non-infectious uveitis are treated with biologics targeting the pro-inflammatory molecule tumour necrosis factor-α (TNF), i.e. TNF inhibitors. Up to one third of the patients do, however, not respond to biologics and lifestyle is assumed to affect the treatment outcome. However, little is known on the effects of lifestyle as a prognostic factor (possibly enabling personalised medicine). The aims of this multidisciplinary collaboration are to identify lifestyle factors that support individualised forecasting of optimised treatment outcome on these costly drugs.

This prospective cohort study will enrol CID patients assigned for biologic treatment. At baseline (Pre-treatment), patient characteristics are assessed using patient-reported outcome measures and clinical assessments on disease activity, quality of life, and lifestyle together with registry data on comorbidity and medication. Follow-up will be conducted at week 14-16 after treatment initiation (according to the current Danish standards). Evaluation of a successful treatment outcome response will - for each disease - be based on most frequently used primary endpoints; the major outcome of the analyses will be to detect differences in treatment outcome between patients with specific lifestyle characteristics.

The overarching goal of this project is to improve the lives of patients suffering from CID, by providing evidence to support dietary recommendations likely to improve the clinical outcome.

The study is approved by the local Ethics Committee (S-20160124) and the local Data Agency (2008-58-035). The study findings will be disseminated in peer-reviewed journals, via patient associations, and presented at national and international conferences.

Detailed description: Chronic inflammatory diseases (CID), including inflammatory bowel diseases (IBD) (of which Crohn's disease \[CD\] and ulcerative colitis \[UC\] are the two most prevailed entities), rheumatic conditions (rheumatoid arthritis \[RA\], axial spondyloarthropathy \[axSpA\], psoriatic arthritis \[PsA\]), skin diseases (psoriasis \[PsO\], hidradenitis suppurativa \[HS\]), and eye disease (non-infectious uveitis \[NiU\]), are diseases of the immune system that are managed with biological agents targeting the pro-inflammatory cytokine tumour necrosis factor-α (TNF), i.e. TNF inhibitors.

Design In this prospective cohort study disease activity prior to and after (14-16 weeks) initiation of biologic treatment will be assessed. The endpoint is the treatment outcome defined as A: Responder according to the specific criteria described below (incl. drug-continuation) or B: Non-responder (incl. drug-discontinuation due to unacceptable side effects). Whether a patient will discontinue therapy is assumed to be based on a certain degree of shared decision making between the patient and physician supported by principles from national guidelines for each CID as recommended in the respective national guidelines and laboratory data.

Setting All patients assigned for initiation of biologic treatment at 1) Department of Gastroenterology and Hepatology, Aalborg University Hospital; 2) Department of Hepatology and Gastroenterology, Aarhus University Hospital; 3) Diagnostic Centre, Silkeborg Regional Hospital; 4) Department of Internal Medicine, Herning Regional Hospital; 5) Department of Gastroenterology, Herlev Hospital; 6) Organ Centre, Hospital of Southern Jutland; 7) Department of Gastroenterology Hospital of South West Jutland; 8) Department of Medical Gastroenterology, Department of Rheumatology, Department of Dermatology and Allergy Centre, and Department of Ophthalmology, Odense University Hospital from 1st of April 2017 and until 31th of Marts 2019 or until a minimum of 100 patients with IBD, 100 patients with RA, and 120 patients with axSpA, PsA, PsO, HS and NiU are achieved.

Clinical data consist of personal data, data on health and disease, lifestyle, laboratory measure, and disease activity scores including using patient-reported outcome measures (PROMs), clinical assessments, and laboratory data. Each participant will fill out validated questionnaires on disease activity, quality of life, and lifestyle using an electronic link. Studies have found electronic questionnaires to be equivalent to paper-based in relation to PROMs.

Data management The electronic questionnaire is in Danish language and the participants will have access to the questionnaire by an electronic link sent to their personal, electronic mailbox. All data will be stored in a secure research storage facility. Information registered by clinicians and technicians will be transferred from paper format to electronic format using either double entry of data or automated forms processing.

Statistical methods The investigators will use this rigorously designed, prospective cohort study to explore the ability to predict clinical response across the conditions included (Y=primary endpoint), and explore whether patients who are on a diet high in fibre AND low in red and processed meat (X=assessed at baseline) is an informative prognostic factor. Per default, the statistical model will include condition (any of the CID conditions included), and clinical centre (site #1 to #8) as fixed effects.

Sample size considerations: It is a well-known difficulty for exploratory prognostic factor research studies like this, to formalize how many participants (i.e. with events) to include. In order to consider an adequate number of outcome events, the investigators apply "the rule of thumb" that dictates that 10 outcome events are needed for each independent variable (possible predictors); the investigators plan to enrol 320 patients in total, and anticipate that 50% of these will experience a clinical response during the 14-16 week period after therapy is initiated. With this in mind: Anticipating that at least 160 will achieve clinical responses (among the 320 patients), this study will have a reasonable power to explore the impact of as many as 16 independent (predictor) variables (including condition and clinical centre).

Focusing on the contrast between groups, for a comparison of two independent binomial proportions (those with high fibre AND low meat intake vs other) using Pearson's Chi-square statistic with a Chi-square approximation with a two-sided significance level of 0.05 (P\<0.05), a total sample size of 318 assuming an allocation ratio of 1 to 2 has an approximate power of 0.924 (i.e. \>90% statistical power) when the proportions responding are 60% and 40%, respectively.

All the statistical programming will be done in SAS (Statistical Analysis Software), STATA or R, transparently reporting the source code used to analyse the data. All computational details will be available in the pre-specified Statistical Analysis Plan (will be finalised before data collection is complete).

Project organisation The project is organised with a Clinical Research Group and an Analytical Research Group. The clinical group includes specialists from the medical, gastroenterological, rheumatological, dermatological and ophthalmological departments that are sampling the cohort. The analytical group will perform the analyses on the biological material.

Eligibility criteria: Inclusion Criteria:

* diagnosed with chronic inflammatory disease
* initiation of targeted therapy
* able to read and understand Danish

Exclusion Criteria:

• not mentally able to reply the questionnaire

Primary outcomes:
measure: Clinical response to therapy depending on condition
timeFrame: week 14-16
Secondary outcomes:
measure: Crohns disease: Disease-specific core outcome sets-1
timeFrame: week 14-16
measure: Crohns disease: Disease-specific core outcome sets-2
timeFrame: week 14-16
measure: Crohns disease: Disease-specific core outcome sets-3
timeFrame: week 14-16
measure: Crohns disease: Disease-specific core outcome sets-4
timeFrame: week 14-16
measure: Crohns disease: Disease-specific core outcome sets-5
timeFrame: week 14-16
measure: Crohns disease: Disease-specific core outcome sets-6
timeFrame: week 14-16
measure: Ulcerative Colitis: Disease-specific core outcome sets-1
timeFrame: week 14-16
measure: Ulcerative Colitis: Disease-specific core outcome sets-2
timeFrame: week 14-16
measure: Ulcerative Colitis: Disease-specific core outcome sets-3
timeFrame: week 14-16
measure: Ulcerative Colitis: Disease-specific core outcome sets-4
timeFrame: week 14-16
measure: Ulcerative Colitis: Disease-specific core outcome sets-5
timeFrame: week 14-16
measure: Ulcerative Colitis: Disease-specific core outcome sets-6
timeFrame: week 14-16
measure: Ulcerative Colitis: Disease-specific core outcome sets-7
timeFrame: week 14-16
measure: Rheumatoid Arthritis: Disease-specific core outcome sets-1
timeFrame: week 14-16
measure: Rheumatoid Arthritis: Disease-specific core outcome sets-2
timeFrame: week 14-16
measure: Rheumatoid Arthritis: Disease-specific core outcome sets-3
timeFrame: week 14-16
measure: Rheumatoid Arthritis: Disease-specific core outcome sets-4
timeFrame: week 14-16
measure: Rheumatoid Arthritis: Disease-specific core outcome sets-5
timeFrame: week 14-16
measure: Rheumatoid Arthritis: Disease-specific core outcome sets-6
timeFrame: week 14-16
measure: Rheumatoid Arthritis: Disease-specific core outcome sets-7
timeFrame: week 14-16
measure: Rheumatoid Arthritis: Disease-specific core outcome sets-8
timeFrame: week 14-16
measure: Rheumatoid Arthritis: Disease-specific core outcome sets-9
timeFrame: week 14-16
measure: Axial Spondyloarthropathy: Disease-specific core outcome sets-1
timeFrame: week 14-16
measure: Axial Spondyloarthropathy: Disease-specific core outcome sets-2
timeFrame: week 14-16
measure: Axial Spondyloarthropathy: Disease-specific core outcome sets-3
timeFrame: week 14-16
measure: Axial Spondyloarthropathy: Disease-specific core outcome sets-4
timeFrame: week 14-16
measure: Axial Spondyloarthropathy: Disease-specific core outcome sets-5
timeFrame: week 14-16
measure: Axial Spondyloarthropathy: Disease-specific core outcome sets-6
timeFrame: week 14-16
measure: Axial Spondyloarthropathy: Disease-specific core outcome sets-7
timeFrame: week 14-16
measure: Psoriatic Arthritis: Disease-specific core outcome sets-1
timeFrame: week 14-16
measure: Psoriatic Arthritis: Disease-specific core outcome sets-2
timeFrame: week 14-16
measure: Psoriatic Arthritis: Disease-specific core outcome sets-3
timeFrame: week 14-16
measure: Psoriatic Arthritis: Disease-specific core outcome sets-4
timeFrame: week 14-16
measure: Psoriatic Arthritis: Disease-specific core outcome sets-5
timeFrame: week 14-16
measure: Psoriatic Arthritis: Disease-specific core outcome sets-6
timeFrame: week 14-16
measure: Psoriatic Arthritis: Disease-specific core outcome sets-7
timeFrame: week 14-16
measure: Psoriatic Arthritis: Disease-specific core outcome sets-8
timeFrame: week 14-16
measure: Psoriatic Arthritis: Disease-specific core outcome sets-9
timeFrame: week 14-16
measure: Psoriatic Arthritis: Disease-specific core outcome sets-10
timeFrame: week 14-16
measure: Psoriasis: Disease-specific core outcome sets-1
timeFrame: week 14-16
measure: Psoriasis: Disease-specific core outcome sets-2
timeFrame: week 14-16
measure: Psoriasis: Disease-specific core outcome sets-3
timeFrame: week 14-16
measure: Psoriasis: Disease-specific core outcome sets-4
timeFrame: week 14-16
measure: Hidradenitis Suppurativa: Disease-specific core outcome sets-1
timeFrame: week 14-16
measure: Hidradenitis Suppurativa: Disease-specific core outcome sets-2
timeFrame: week 14-16
measure: Hidradenitis Suppurativa: Disease-specific core outcome sets-3
timeFrame: week 14-16
measure: Non-Infectious Uveitis: Disease-specific core outcome sets-1
timeFrame: week 14-16
measure: Non-Infectious Uveitis: Disease-specific core outcome sets-2
timeFrame: week 14-16
measure: Non-Infectious Uveitis: Disease-specific core outcome sets-3
timeFrame: week 14-16
measure: Health-related quality of life-1
timeFrame: week 14-16
measure: Health-related quality of life and disability-2
timeFrame: week 14-16
measure: Health-related quality of life-2
timeFrame: week 14-16
measure: Global assessment-1
timeFrame: week 14-16
measure: Global assessment-2
timeFrame: week 14-16
Other outcomes:
measure: Exploratory outcome measure - Serious adverse events
timeFrame: week 14-16
measure: Biological response
timeFrame: week 14-16
Locations:
city: Aabenraa
country: Denmark
facility: Hospital of Southern Jutland
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
Study officials:
affiliation: University of Southern Denmark
name: Vibeke Andersen, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Overgaard SH, Sorensen SB, Munk HL, Nexoe AB, Glerup H, Henriksen RH, Guldmann T, Pedersen N, Saboori S, Hvid L, Dahlerup JF, Hvas CL, Jawhara M, Andersen KW, Pedersen AK, Nielsen OH, Bergenheim F, Brodersen JB, Heitmann BL, Halldorsson TI, Holmskov U, Bygum A, Christensen R, Kjeldsen J, Ellingsen T, Andersen V. Impact of fibre and red/processed meat intake on treatment outcomes among patients with chronic inflammatory diseases initiating biological therapy: A prospective cohort study. Front Nutr. 2022 Oct 13;9:985732. doi: 10.3389/fnut.2022.985732. eCollection 2022.
citation: Christensen R, Heitmann BL, Andersen KW, Nielsen OH, Sorensen SB, Jawhara M, Bygum A, Hvid L, Grauslund J, Wied J, Glerup H, Fredberg U, Villadsen JA, Kjaer SG, Fallingborg J, Moghadd SAGR, Knudsen T, Brodersen J, Frojk J, Dahlerup JF, Bojesen AB, Sorensen GL, Thiel S, Faergeman NJ, Brandslund I, Bennike TB, Stensballe A, Schmidt EB, Franke A, Ellinghaus D, Rosenstiel P, Raes J, Boye M, Werner L, Nielsen CL, Munk HL, Nexoe AB, Ellingsen T, Holmskov U, Kjeldsen J, Andersen V. Impact of red and processed meat and fibre intake on treatment outcomes among patients with chronic inflammatory diseases: protocol for a prospective cohort study of prognostic factors and personalised medicine. BMJ Open. 2018 Feb 8;8(2):e018166. doi: 10.1136/bmjopen-2017-018166.