Evaluation of the Effect of the Mediterranean Diet on Disease Activity and Treatment Response in Patients With Axial Spondyloarthritis Receiving Biologic Therapy
Phase: NA
Conditions: Axial Spondyloarthritis (Ankylosing Spondylitis)
Sponsor: Sinem Kübra Beke

Study Protocol
Official
Title:
Evaluation of the Effect of the Mediterranean Diet on Disease Activity and Treatment Response
in Patients With Axial Spondyloarthritis Receiving Biologic Therapy
Protocol Number: AS01
Sponsor/Institution:
Erciyes University, Faculty of Medicine, Department of Physical Medicine and Rehabilitation,
Division of Rheumatology
Principal
Investigator:
Assoc. Prof. Gizem Cengiz
Date:
24 January 2025
Aim
This study aims to investigate the effects of the Mediterranean diet on disease activity, quality
of life, inflammation levels, pain scores, and the frequency of biologic DMARD (bDMARD)
use in patients with ankylosing spondylitis (AS) receiving biologic therapy.
Potential Risks
There are no anticipated risks associated with this study.
Background
Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown etiology that
typically begins with inflammation in the sacroiliac joints in the early stages and later affects
the axial spine.¹ It can lead to significant reductions in quality of life due to inflammatory back
pain, structural, and functional impairments. Genetic factors, gut microbiota, mechanical effects
on the spine and peripheral joints, innate immunity, oxidative stress, lifestyle, and
environmental factors are thought to play an important role in AS pathogenesis.² Accordingly,
diet has increasingly been investigated as a potential factor influencing the pathogenesis and
progression of AS.
Both
pharmacological
and
non-pharmacological
approaches
should
be
used
in
AS
management.³ The main goals of treatment are to control symptoms and inflammation, prevent

structural damage progression, and maximize quality of life.⁴ However, there is limited
evidence supporting the impact of lifestyle modifications. Among environmental factors, diet
stands out as a modifiable factor with potential to reduce inflammation.⁵ Inflammation can alter
metabolism, potentially modifying dietary habits and directly influencing disease activity.⁶
While some foods may trigger inflammatory processes, nutrients such as antioxidants and
omega-3 fatty acids demonstrate anti-inflammatory properties.
A study on axial spondyloarthritis (axSpA) patients suggested that diet could have beneficial
effects; however, this study also included axSpA patients beyond AS.⁷ Diets rich in fiber and
antioxidants may provide protective effects in gastrointestinal and inflammatory processes.⁸
The Mediterranean diet (MD), with its anti-inflammatory and antioxidant potential, is thought
to delay the onset and progression of chronic inflammation.⁹ This diet has also been linked to
the prevention and management of cardiovascular diseases.¹⁰ The MD includes high intake of
olive oil, unrefined carbohydrates, fresh and dried fruits, vegetables, and fish; low intake of
dairy products and red meat; and moderate consumption of red wine. It is particularly rich in
antioxidants and polyunsaturated fats.
In AS, these nutritional components may reduce inflammation, pain, and structural damage,
and potentially lower disease prevalence.⁷ However, to date, no study has compared the effects
of the Mediterranean diet in AS patients receiving bDMARDs with a control group. Therefore,
our study aims to evaluate the efficacy of the Mediterranean diet in this patient group,
contributing to disease management and supporting a therapeutic approach that improves
quality of life.
Hypothesis:
The Mediterranean diet will reduce disease activity, improve quality of life, and decrease
inflammation in AS patients.
Methods
Study Design and Participants
This is a prospective, single-blind, randomized controlled trial.

Sample size calculation determined that 51 participants per group were required. With an
additional 10% dropout allowance, the total target enrollment is 55 participants per group (110
total). Eligible participants will be adults over 18 years old, diagnosed with AS according to
ASAS criteria, and providing written informed consent.
Inclusion Criteria:
1. Diagnosis of AS according to ASAS criteria
2. Age ≥18 years
3. No recent dietary changes in the past 3 months
4. Stable treatment with NSAIDs or DMARDs in the past 4 months
5. Voluntary participation with signed informed consent
Exclusion Criteria:
1. Pregnancy or breastfeeding
2. Dietary restrictions preventing adherence to the Mediterranean diet (e.g., severe food
allergies)
3. Participation in another diet or exercise-based intervention within the past 6 months
4. History of another rheumatologic or neurological disorder
Randomization
Participants will be randomized into intervention and control groups using stratified
randomization by age, body mass index, and disease activity (ASDAS-CRP). Randomization
will be conducted through https://www.randomizer.org/ by an independent researcher not
involved in the study.
Outcome assessors will be blinded to group allocation. The physiotherapist implementing the
intervention will not be blinded, but will not participate in outcome assessments.
Interventions


Control Group (Standard Care): Patients will continue their standard medical
treatment and receive general healthy nutrition recommendations.

Mediterranean Diet Group: Patients will follow a Mediterranean diet plan supervised
by a dietitian. Compliance will be monitored via phone calls every 10 days.
Assessments will be performed at baseline and at 3 months.
Outcomes
Primary Outcome Measure:

Change in Ankylosing Spondylitis Disease Activity Score with C-reactive protein
(ASDAS-CRP) from baseline to 3 months.¹³
Secondary Outcome Measures:

Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)¹¹ ¹²

Bath Ankylosing Spondylitis Functional Index (BASFI)

Bath Ankylosing Spondylitis Metrology Index (BASMI)

Hospital Anxiety and Depression Scale (HADS)¹⁴ ¹⁵

Short Form-36 (SF-36)¹⁶

International Physical Activity Questionnaire (IPAQ)¹⁷

Pittsburgh Sleep Quality Index (PSQI)¹⁸

FACIT-Fatigue Scale¹⁹

Health Assessment Questionnaire (HAQ)²⁰

Morisky Medication Adherence Scale-8 (MMAS-8)²¹ ²²

PREDIMED Mediterranean Diet Adherence Questionnaire²³ ²⁴

Handgrip strength (Jamar Hydraulic Hand Dynamometer)

Body composition (InBody270 Analyzer)

Statistical Analysis
Sample size was calculated using G*Power version 3.1.9.7 with 80% power and a 5% type I
error, yielding 51 participants per group. With a 10% dropout rate, 55 participants per group
will be recruited.
All analyses will be conducted using SPSS version 22.0. Normality will be tested with Shapiro-
Wilk. Baseline group comparisons will be done using independent t-tests or Mann-Whitney U
tests. Repeated measures will be analyzed with mixed-model ANOVA, with Bonferroni
correction for multiple comparisons. Categorical variables will be analyzed using Chi-square
or Fisher’s exact tests. A p-value <0.05 will be considered statistically significant.
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