Chronic Inflammatory Disease, Lifestyle and Treatment Response

Psoriasis Clinical Trial

— BELIEVE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03173144
• Other study ID #: MOK1
• Secondary ID: 733100KBF nr. 20
• Status: Completed
• Start date: September 21, 2017
• Est. completion date: April 30, 2021

Study information

• Verified date: June 2021
• Source: University of Southern Denmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 233
• Est. completion date: April 30, 2021
• Est. primary completion date: July 22, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Psoriatic
• Arthritis, Psoriatic (PsA)
• Arthritis, Rheumatoid
• Arthritis, Rheumatoid (RA)
• Autoimmune Diseases
• Colitis, Ulcerative
• Colitis, Ulcerative (UC)
• Crohn Disease
• Crohn Disease (CD)
• Hidradenitis
• Hidradenitis Suppurativa
• Hidradenitis Suppurativa (HS)
• Inflammatory Bowel Diseases
• Psoriasis
• Spondylarthropathies
• Uveitis

Intervention

Other:
• Primary exposure variable
Upper tertile (33.3% of the total sample) based on the ratio: fibre/meat intake is associated with better treatment outcome Low intake of red and processed meat (defined as below the lower tertile [33.3% of the total sample]) and high intake of dietary fibres (defined as those above the upper tertile [33.3% of the total sample]) are independently associated with better treatment outcome, and their synergy (interaction between the factors meat and fibres) gives the best treatment outcome
• Other (exploratory) exposure variables
Lifestyle factors independently or combined (red and processed meat, vegetable, dietary fibre, cereals, gluten, legumes, red wine, dairy products, physical activity, smoking, total protein/ fat, protein/ fat from red and processed meat, glucemic index) Pretreatment lifestyle-associated biomarkers Combinations of lifestyle factors and lifestyle-associated biomarkers Gene-environment interaction analyses Pretreatment levels of inflammatory molecules

Locations

Country	Name	City	State
Denmark	Hospital of Southern Jutland	Aabenraa
Denmark	Herlev Hospital	Herlev
Denmark	Odense University Hospital	Odense

Sponsors (17)

Lead Sponsor

Collaborator

University of Southern Denmark

Aalborg University, Aalborg University Hospital, Aarhus University Hospital, Colitis-Crohn Foreningen, Herlev Hospital, Herning Hospital, Hospital of South West Jutland, Hospital of Southern Jutland, Odense University Hospital, Regionshospitalet Silkeborg, Sygehus Lillebaelt, The Danish Psoriasis Association, University Hospital Bispebjerg and Frederiksberg, University of Aarhus, University of Copenhagen, University of Kiel

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory outcome measure - Serious adverse events	• Serious adverse events (y/n)	week 14-16
Other	Biological response	• CRP (mg/l)	week 14-16
Primary	Clinical response to therapy depending on condition	The predefined primary endpoint will be the proportion of patients with clinical response to therapy at first clinical follow-up.; Crohn's disease: HBI of 4 or less; Ulcerative colitis: Mayo Clinic Score of 2 or less (with no individual subscore of >1); Rheumatoid arthritis: ACR20; Axial spondyloarthritis: ASAS20; Psoriatic arthritis: ACR20; Psoriasis: PASI75; Hidradenitis suppurativa: HiSCR; Uveitis: those who did not have a treatment failure	week 14-16
Secondary	Crohns disease: Disease-specific core outcome sets-1	• STRIDE (y/n)	week 14-16
Secondary	Crohns disease: Disease-specific core outcome sets-2	• HBI (score)	week 14-16
Secondary	Crohns disease: Disease-specific core outcome sets-3	• Physician global assessment (score)	week 14-16
Secondary	Crohns disease: Disease-specific core outcome sets-4	• Number of draining fistulas (only fistulising CD) (number)	week 14-16
Secondary	Crohns disease: Disease-specific core outcome sets-5	• Corticosteroid-Free Remission (y/n)	week 14-16
Secondary	Crohns disease: Disease-specific core outcome sets-6	• Supplemental medication (y/n)	week 14-16
Secondary	Ulcerative Colitis: Disease-specific core outcome sets-1	• STRIDE criteria (y/n)	week 14-16
Secondary	Ulcerative Colitis: Disease-specific core outcome sets-2	• Mayo Clinical Score (score)	week 14-16
Secondary	Ulcerative Colitis: Disease-specific core outcome sets-3	• Mayo "normal mucosal appearance" (y/n)	week 14-16
Secondary	Ulcerative Colitis: Disease-specific core outcome sets-4	• Mayo clinical response (y/n)	week 14-16
Secondary	Ulcerative Colitis: Disease-specific core outcome sets-5	• SCCAI (score)	week 14-16
Secondary	Ulcerative Colitis: Disease-specific core outcome sets-6	• Corticosteroid-Free Remission (y/n)	week 14-16
Secondary	Ulcerative Colitis: Disease-specific core outcome sets-7	• Supplemental medication (y/n)	week 14-16
Secondary	Rheumatoid Arthritis: Disease-specific core outcome sets-1	• Tender joints (number)	week 14-16
Secondary	Rheumatoid Arthritis: Disease-specific core outcome sets-2	• Swollen joints (number)	week 14-16
Secondary	Rheumatoid Arthritis: Disease-specific core outcome sets-3	• Pain (0-100 mm VAS)	week 14-16
Secondary	Rheumatoid Arthritis: Disease-specific core outcome sets-4	• Physician global assessment (0-100 mm VAS)	week 14-16
Secondary	Rheumatoid Arthritis: Disease-specific core outcome sets-5	• Patient global assessment (0-100 mm VAS)	week 14-16
Secondary	Rheumatoid Arthritis: Disease-specific core outcome sets-6	• HAQ-DI (score)	week 14-16
Secondary	Rheumatoid Arthritis: Disease-specific core outcome sets-7	• C-Reactive protein (mg/l)	week 14-16
Secondary	Rheumatoid Arthritis: Disease-specific core outcome sets-8	• DAS28-CRP (score)	week 14-16
Secondary	Rheumatoid Arthritis: Disease-specific core outcome sets-9	• Simplified Disease Activity Index (SDAI) (index)	week 14-16
Secondary	Axial Spondyloarthropathy: Disease-specific core outcome sets-1	• BASFI (score)	week 14-16
Secondary	Axial Spondyloarthropathy: Disease-specific core outcome sets-2	• BASDAI (score)	week 14-16
Secondary	Axial Spondyloarthropathy: Disease-specific core outcome sets-3	• BASMI (score)	week 14-16
Secondary	Axial Spondyloarthropathy: Disease-specific core outcome sets-4	• Total score for back pain (0-100 mm VAS)	week 14-16
Secondary	Axial Spondyloarthropathy: Disease-specific core outcome sets-5	• Physician global assessment (0-100 mm VAS)	week 14-16
Secondary	Axial Spondyloarthropathy: Disease-specific core outcome sets-6	• Patient global assessment (0-100 mm VAS)	week 14-16
Secondary	Axial Spondyloarthropathy: Disease-specific core outcome sets-7	• C-Reactive protein (mg/l)	week 14-16
Secondary	Psoriatic Arthritis: Disease-specific core outcome sets-1	• Tender joints (number)	week 14-16
Secondary	Psoriatic Arthritis: Disease-specific core outcome sets-2	• Swollen joints (number)	week 14-16
Secondary	Psoriatic Arthritis: Disease-specific core outcome sets-3	• Psoriatic Arthritis Pain VAS (0-100 mm VAS)	week 14-16
Secondary	Psoriatic Arthritis: Disease-specific core outcome sets-4	• Physician global assessment (0-100 mm VAS)	week 14-16
Secondary	Psoriatic Arthritis: Disease-specific core outcome sets-5	• Patient global assessment (0-100 mm VAS)	week 14-16
Secondary	Psoriatic Arthritis: Disease-specific core outcome sets-6	• HAQ-DI (score)	week 14-16
Secondary	Psoriatic Arthritis: Disease-specific core outcome sets-7	• C-Reactive protein (mg/l)	week 14-16
Secondary	Psoriatic Arthritis: Disease-specific core outcome sets-8	• DAS28-CRP (score)	week 14-16
Secondary	Psoriatic Arthritis: Disease-specific core outcome sets-9	• Simplified Disease Activity Index (SDAI)(score)	week 14-16
Secondary	Psoriatic Arthritis: Disease-specific core outcome sets-10	• PASI (score)	week 14-16
Secondary	Psoriasis: Disease-specific core outcome sets-1	• PASI (score)	week 14-16
Secondary	Psoriasis: Disease-specific core outcome sets-2	• Physician global assessment (0-100 mm VAS)	week 14-16
Secondary	Psoriasis: Disease-specific core outcome sets-3	• Patient global assessment (0-100 mm VAS)	week 14-16
Secondary	Psoriasis: Disease-specific core outcome sets-4	• Dermatology Life Quality Index (DLQI) Total Score (score)	week 14-16
Secondary	Hidradenitis Suppurativa: Disease-specific core outcome sets-1	• Participants who achieve Abscess and Inflammatory Nodule (AN) Count of 0, 1, and 2, respectively (score)	week 14-16
Secondary	Hidradenitis Suppurativa: Disease-specific core outcome sets-2	• Patient's Global Assessment of Skin Pain (0-100 mm VAS)	week 14-16
Secondary	Hidradenitis Suppurativa: Disease-specific core outcome sets-3	• Modified Sartorius Score (score)	week 14-16
Secondary	Non-Infectious Uveitis: Disease-specific core outcome sets-1	• New active, inflammatory chorioretinal or retinal vascular lesions relative to Baseline (y/n)	week 14-16
Secondary	Non-Infectious Uveitis: Disease-specific core outcome sets-2	• Inability to achieve = 0.5+ or a 2-step increase relative to best state achieved at all visits in anterior chamber cell grade or vitreous haze grade (y/n)	week 14-16
Secondary	Non-Infectious Uveitis: Disease-specific core outcome sets-3	• Worsening of best corrected visual acuity by = 15 letters relative to best state achieved (y/n)	week 14-16
Secondary	Health-related quality of life-1	• SF12 (Short Form Health Survey) (score)	week 14-16
Secondary	Health-related quality of life and disability-2	• SHS (Short Health Scale) (score)	week 14-16
Secondary	Health-related quality of life-2	• SHS (Short Health Scale) (score)	week 14-16
Secondary	Global assessment-1	• Physician global assessment (0-100 mm VAS)	week 14-16
Secondary	Global assessment-2	• Patient global assessment (0-100 mm VAS)	week 14-16