Subclinical intestinal inflammation and intestinal permeability have been reported in patients with ankylosing spondylitis. Gluten is one of the main triggers of zonulin releaseand gluten intake may contribute to the development of the disease by increasing intestinal permeability. This study aims to determine the impacts of a gluten-freediet on intestinal permeability, sub-clinical intestinal inflammation, disease activity, functional status and quality of life in patients with ankylosing spondylitis. The main questions it aims to answer are: Does a gluten-free diet have an effect on disease activity and functional status in patients with ankylosing spondylitis? Does a gluten-free diet have an effect on intestinal permeability and subclinical intestinal inflammation in patients with ankylosing spondylitis? The investigators will evaluate the effects of the gluten-free diet compared to a control group.
Ankylosing Spondylitis (AS) is a chronic, progressive, inflammatory rheumatic disease that severely impairs patients' quality of life and functional capacity. The gut-joint axis theory in the pathogenesis of AS is gaining increasing support. Specifically, the increase in intestinal permeability mediated by zonulin, and the subsequent leakage of bacterial products (e.g., LPS) into the circulation, is recognized as a central mechanism in many diseases, including AS. Gluten has been proven to be one of the most potent dietary triggers of zonulin release, independent of genetic predisposition. Despite this, the clinical effects of a gluten-free diet (GFD) on this specific mechanism and its potential in AS patients have not yet been fully elucidated. Although indirect evidence suggesting that a GFD may provide clinical improvement in AS patients is accumulating, there are no studies in the literature that directly test the underlying biological mechanism (zonulin → LPS → systemic inflammation). This represents a critical knowledge gap that prevents clinicians from providing evidence-based dietary recommendations to patients. Therefore, investigators basically propose two hypotheses. Hypothesis 1: An 8-week gluten-free diet in patients with Ankylosing Spondylitis will improve intestinal barrier integrity by reducing gliadin-induced zonulin release. Hypothesis 2: The reduction in intestinal permeability will decrease the amount of lipopolysaccharide (LPS) translocating into the circulation and the subsequent pro-inflammatory cytokine response (TNF-α, IL-6). Consequently, this mechanism will lead to a measurable clinical improvement in disease activity (BASDAI) and quality of life (ASQoL). To this end, an 8-week, randomized controlled prospective intervention study has been designed, which will include 60 AS patients aged 18-64. The intervention group (Gluten-Free Diet Group, n=30) will follow a gluten-free diet for 8 weeks in addition to their current treatments. The daily energy requirement for patients in this group will be calculated (using the Harris-Benedict equation for basal metabolic rate, adjusted for physical activity levels), and a gluten-free diet will be planned accordingly. In the initial face-to-face meeting, a dietitian will explain how to properly adhere to participants the gluten-free diet.Compliance will be monitored by the dietitian at weeks 2, 4, and 6 using a 1-day food record. Patients who do not adhere to the gluten-free diet will be excluded from the study. The control group (n=30) will continue with their current standard clinical follow-up without any dietary intervention. Disease activity, functional status, gastrointestinal symptoms, and quality of life will be assessed using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), the Gastrointestinal Symptom Rating Scale (GSRS), and the Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire. All biochemical measurements will be performed at baseline and at the end of the 8th week. This design will allow us to evaluate whether a GFD provides an additional benefit to standard care in real-world clinical practice. The primary objective of the study is to measure the effect of a GFD on markers of intestinal permeability (serum zonulin) and microbial translocation (serum LPS). The secondary objectives are to evaluate the reflections of this mechanistic change on systemic inflammation markers (CRP, TNF-α, IL-6) and clinical disease activity scores (BASDAI, ASQoL). Measurements will be performed using validated ELISA methods and standard clinical questionnaires. The primary novelty of this project is that it will be one of the first studies to explain the efficacy of a GFD in AS patients by targeting the underlying biological mechanism (zonulin → LPS → inflammation). The findings obtained at the end of the project will contribute to the development of evidence-based dietary recommendations for the management of AS.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
NONE
Enrollment
60
Patients in the experimental arm will received a gluten-free diet for 8 weeks.
Bakırköy Dr. Sadi Konuk Training and Research hospital
Istanbul, Turkey (Türkiye)
RECRUITINGİstanbul Medeniyet University
Istanbul, Turkey (Türkiye)
ACTIVE_NOT_RECRUITINGİstanbul Sağlık Bilimleri University
Istanbul, Turkey (Türkiye)
ACTIVE_NOT_RECRUITINGMarmara University
Istanbul, Turkey (Türkiye)
ACTIVE_NOT_RECRUITINGeffects of a 8-week Gluten Free Diet versus placebo diet on fasting serum zonulin levels
Serum zonulin will be evaluated as a biomarker of intestinal permeability. It will be measured by ELISA(enzyme-linked immunosorbent assay) method.
Time frame: Change from baseline serum zonulin at 8 weeks
effects of a 8-week Gluten Free Diet versus placebo diet on fasting serum LPS levels
Serum LPS will be evaluated as a biomarker of intestinal permeability. It will be measured by ELISA(enzyme-linked immunosorbent assay) method.
Time frame: Change from baseline serum LPS at 8 weeks
effects of a 8 week Gluten Free Diet versus placebo diet on the activity of Ankylosing Spondylitis evaluated by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI).
The BASDAI consists of a 0 - 10 scale measuring discomfort, pain, and fatigue (0 being no problem and 10 being the worst problem) in response to six questions. The resulting 0 to 50 score is divided by 5 to give a final 0 - 10 BASDAI score. Scores of 4 or greater suggest suboptimal control of disease,
Time frame: Change from baseline BASDAI score at 8 weeks
effects of a 8-week Gluten Free Diet versus placebo diet on functional disability asssessed by Bath Ankylosing Spondylitis Functionnal Index (BASFI) questionnaire
Functional disability index consisting of 10 questions. After taking the answer of each question out of 10, the total of the points was calculated by dividing the number of questions. The higher the score, the greater the handicap.
Time frame: Change from baseline BASFI score at 8 weeks
effects of a 8 week Gluten Free Diet versus placebo diet on the quality of life of Ankylosing Spondylitis evaluated by the Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL).
It evaluates quality of life. Each statement on the ASQoL (18-item) is given a score of "1" or "0". A score of "1" is given where the item is affirmed, indicating adverse QoL. All item scores are summed to give a total score or index. Scores can range from 0 (good QoL) to 18 (poor QoL).
Time frame: Change from baseline ASQoL score at 8 weeks
effects of a 8-week Gluten Free Diet versus placebo diet on CRP levels
A c-reactive protein test measures the level of c-reactive protein (CRP) in your blood. CRP is a protein made by your liver. It's sent into your bloodstream in response to inflammation. Normally, you have low levels of c-reactive protein in your blood. High levels may be sign of a serious infection or other disorder.
Time frame: Change from baseline CRP at 8 weeks
effects of a 8-week Gluten Free Diet versus placebo diet on ESR levels
An ESR is a type of blood test that measures how quickly erythrocytes settle at the bottom of a test tube that contains a blood sample. Normally, red blood cells settle relatively slowly. A faster-than-normal rate may indicate inflammation in the body.
Time frame: Change from baseline ESR at 8 weeks
effects of a 8 week gluten free diet versus placebo diet on the gastrointestinal symptoms
Validated seven point questionnaire that assesses gastrointestinal symptoms for five symptom areas, including abdominal pain, reflux, indigestion, diarrhea, and constipation. Individual scores are calculated for each symptom area and the mean of the scores is used to derive an overall GSRS score. Scores range from 0-7, with higher scores indicating gastrointestinal discomfort.
Time frame: Change from baseline GSRS score at 8 weeks
change in body weight
Body weight will be measured with a bathroom scale.
Time frame: Change from baseline body weight at 8 weeks
change in Body Mass Index
The BMI will be calculated by the formula (height/weight²).
Time frame: Change from baseline BMI at 8 weeks
effects of a 8-week Gluten Free Diet versus placebo diet on fasting glucose levels
Glucose level testing will be done after an overnight fast.
Time frame: Change from baseline fasting glucose at 8 weeks
effects of a 8-week Gluten Free Diet versus placebo diet on fasting insulin levels
Insuline level testing will be done after an overnight fast.
Time frame: Change from baseline fasting insulin at 8 weeks
effects of a 8-week Gluten Free Diet versus placebo diet on fasting serum calprotectin levels
Serum calprotectin will be evaluated as a biomarker of subclinical intestinal inflammation. It will be measured by ELISA(enzyme-linked immunosorbent assay) method.
Time frame: Change from baseline serum calprotektin at 8 weeks
effects of a 8-week Gluten Free Diet versus placebo diet on fasting serum haptoglobin levels
Haptoglobin is an acute phase reactant. Serum haptoglobin will be evaluated as a biomarker of inflammation. It will be measured by ELISA(enzyme-linked immunosorbent assay) method.
Time frame: Change from baseline serum haptoglobin at 8 weeks
effects of a 8-week Gluten Free Diet versus placebo diet on fasting serum TNF-alpha levels
Serum TNF-alpha will be evaluated as a biomarker of inflammation. It will be measured by ELISA(enzyme-linked immunosorbent assay) method.
Time frame: Change from baseline serum TNF-alpha at 8 weeks
effects of a 8-week Gluten Free Diet versus placebo diet on fasting serum IL-6 levels
Serum IL-6 will be evaluated as a biomarker of inflammation. It will be measured by ELISA(enzyme-linked immunosorbent assay) method.
Time frame: Change from baseline serum IL-6 at 8 weeks
effects of a 8-week Gluten Free Diet versus placebo diet on fasting serum IL-10 levels
Serum IL-10 will be evaluated as a biomarker of inflammation. It will be measured by ELISA(enzyme-linked immunosorbent assay) method.
Time frame: Change from baseline serum IL-10 at 8 weeks
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