Effect of a Low Starch Diet in Patients With Ankylosing Spondylitis

Study Overview
=================
Brief Summary
-----------------
The aim of this study is to explore the effect of a low starch diet (reduction of at least 40%) in the gut bacteria modulation, especially Klebsiella pneumoniae, and its relation to disease activity, functional impairment and quality of life in patients with Ankylosing Spondylitis (AS).

Detailed Description
-----------------
Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease characterized by axial inflammation and with unknown aetiology. The immune system dysregulation is known, where genetic factors play a key role, in particular, the susceptibility associated to the HLA-B27 allele. The presence of this genetic marker, seems to trigger an abnormal response of the individual, under the action of determine microorganisms, and probably, the combination of these two factors may contribute to the manifestation of the disease, through the induction of an immune and cytolytic response, leading to tissue injury and promoting the inflammation. Intestinal microbiota involvement in spondylarthritis is a controversial issue, however, was observed an increased concentration of Klebsiella pneumoniae bacteria in the faeces of AS patients. It has been suggested that an intervention aiming these bacteria's starving could benefit the reduction of the inflammatory processes and be a part of AS treatment. The bowel microflora depends on dietary intake, like undigested starch, for their growth. Some studies have highlighted the relation between the intake of starch and the disease activity. The modulation of the microbiota, particularly, the reduction of Klebsiella, may be beneficial as a complementary approach to AS therapy. A sample of 300 patients with AS, followed-up at Portuguese Institute of Rheumatology in Lisbon, will be randomly assigned in two groups. The group A will adopt a balanced diet based on the general recommendations for healthy eating by the World Health Organization, for a period of 6 weeks. In Group B will be implemented an individual balanced low starch diet, which is characterized by the significant reduction of starchy food, of at least 40% of the total daily ingested starch. The change in biometric data, body composition, intestinal Klebsiella will be related to food intake, disease activity and quality of life assessments. These data will be compared between the 2 groups (diet A versus diet B), obtaining measures on the effect of each diet on the analyzed variables.

Official Title
-----------------
Effect of a Low Starch Diet in the Gut Microbiome Modulation, Disease Activity and Quality of Life in Patients With Ankylosing Spondylitis

Conditions
-----------------
Spondyloarthritis, Ankylosing Spondylitis

Intervention / Treatment
-----------------
* Behavioral: Low Starch Diet (LSD)
* Behavioral: General healthy eating


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age between 18 and 75 years old Available to comply with study protocol Ability to read and sign the Informed Consent Diagnosis of Ankylosing Spondylitis performed by the rheumatologist, according to the ASAS classification criteria, revised in 2016 Positive HLA-B27allele Stable dose therapy within 3 months before selection Exclusion Criteria: Pregnant, breastfeeding or planning to become pregnant within the study period Prior or current clinical history of drug or other substances abuse Subjects with uncontrolled clinical conditions, like neoplastic diseases, renal failure, liver impairment, uncompensated cardiac disease Dietetic restrictions due to religious believes or others incompatible with the study protocol Impossibility to attend to the mandatory personal clinical evaluation Presence of pacemaker, making impossible to perform the impedance body composition analysis Change in therapy during the intervention period

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Starch Diet (LSD)<br>Participants will receive the low starch diet program: restricts the daily amount of ingested rich starch food, to a reduction of at least 40% compared to usual daily individual starch intake. | Behavioral: Low Starch Diet (LSD)<br>* 6-week balanced diet program, adapted to individual energetic needs, with significant reduction of high content starchy food, naturally present in plant cells, roots, tubers, seeds, beans, legumes, fruits, and highly present in most farinaceous grains, especially in potatoes, corn, rice, pasta, bread, cookies and cakes.<br>|
| Active Comparator: Control<br>Participants will receive dietary counselling based on general recommendations for healthy eating. | Behavioral: General healthy eating<br>* 6-week balanced healthy eating counseling program, according to the World Health Organization recommendations.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in intestinal Klebsiella | To compare the mean change of Klebsiella bacteria in faecal samples between the LSD group and the control. | 6 weeks (at baseline and the end of follow-up between the two groups) | 
| Change in mean erythrocyte sedimentation rate (ESR) | Plasma concentrations will be assessed to evaluate ESR, a marker of systemic inflammation that provided insights into the overall anti-inflammatory effect of rheumatologic therapies. Data are presented as mean ESR value in millimeters per hour (mm/hr) ± standard deviation. | 6 weeks (at baseline and the end of follow-up) | 
| Change in mean C-reactive protein (CRP) | Plasma concentrations will be assessed to evaluate CRP, a marker of systemic inflammation that provided insights into the overall anti-inflammatory effect of rheumatologic therapies. Data are presented as mean CRP value in milligrams per liter (mg/L) ± standard deviation. | 6 weeks (at baseline and the end of follow-up) | 
| Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) | The BASDAI is a six question, participant-reported measure of overall disease activity that probed the level of fatigue, neck/back/hip pain, peripheral joint swelling and pain, localized tenderness, as well as morning stiffness severity and duration. The mean measurement (score) of questions 5 and 6 is added to the scores from questions 1 to 4 and divided by 5 to calculate the total BASDAI score. It is scored on a numerical rating scale that ranges from 0 (no symptoms) to 10 (severe symptoms), higher scores indicating severe disability due to AS disease. Data are presented as mean total BASDAI score +/- standard deviation. | 6 weeks (at baseline and the end of follow-up) | 
| Bath Ankylosing Spondylitis Function Index (BASFI) | The BASFI is a self-assessment instrument used to assess function. It comprises 8 specific questions regarding function in AS and 2 questions to identify participant's ability to cope up with everyday life. Each question is answered on a 100 millimeter (mm) horizontal VAS. The mean VAS score gives BASFI score between 0 to 100 where 0=easy to 100=impossible. | 6 weeks (at baseline and the end of follow-up) | 
| Ankylosing Spondylitis Disease Activity Score (ASDAS) | ASDAS includes CRP mg/L; four additional self-reported items (rated on 0-10cm VAS or 0-10 numerical rating scale [NRS]) included are total back pain (TBP), duration of morning stiffness (DMS), peripheral pain/swelling and patient global assessment (PGA). ASDAS scores calculated as: ASDAS(CRP) = (0.121*total back pain) + (0.110*participant global) + (0.073*peripheral pain/swelling) + (0.058* duration of morning stiffness) + (0.579*Ln(CRP+1). The disease activity, TBP, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and DMS on a numeric rating scale (0 to 10, with 0 being none and 10 representing a duration of =>2 hours). Inactive disease is defined as an ASDAS score <1.3. | 6 weeks (at baseline and the end of follow-up) | 
| Bath Ankylosing Spondylitis Patient Global Score (BAS-G) | The self-administered Bath Ankylosing Spondylitis Global (BAS-G) measures global consequences of axial spondyloarthritis, indicating the effect of disease on participant's well-being. This scale is composed of 2 items ranging from 0 = very good to 10 =very bad. Total score ranges from 0 to 10: the higher the BAS-G score, the worse the participant's health status. | 6 weeks (at baseline and the end of follow-up) | 
| Ankylosing Spondylitis Quality of Life (ASQoL) | The Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire is a disease-specific instrument designed to measure the health related quality of life (HRQOL) in participants with AS. Participants answer yes/no to 18 items assessing the current impact of AS on their quality of life status. The total score ranges from 0 to 18, with lower scores representing better AS-specific quality of life. Negative numbers indicate improvement from baseline. | 6 weeks (at baseline and the end of follow-up) | 
| Euro Quality of Life-5D (EQ-5D) | The EQ-5D is a standardized, generic measure of health outcome, designed for self-completion by participants. The EQ-5D includes a descriptive section with 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that are combined into an overall health utilities index, and an NRS (100 mm VAS) that measures perception of overall health, with 0 indicating worst health and 100 representing best imaginable health. | 6 weeks (at baseline, 2-weeks, 4-weeks, end of follow-up) | 
| Change in Short Form (36) Health Survey (SF-36) | SF-36 is a generic 36-item questionnaire measuring health-related quality of life (HRQL) covering 2 summary measures: physical component summary (PCS) and mental component summary (MCS). The SF-36 consists of 8 subscales. The PCS had 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS had 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). Summations of item scores of the same subscale give the subscale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Higher scores indicate better health and well-being. | 6 weeks (at baseline and the end of follow-up) | 
| Change in ASAS response criteria | The Assessment in SpondyloArthritis international Society (ASAS) 20 response is defined as an improvement of >= 20% and absolute improvement of >= 1 unit (on a scale of 0 to 10) from Baseline in at least three of the following four domains, with no deterioration (where deterioration is defined as a worsening of >= 20% and a net worsening of >= 1 units [on a scale of 0 to 10]) in the remaining domains: Patient's Global Assessment, Pain, Function, Inflammation. | 6 weeks (at baseline and the end of follow-up) | 
| Change in pain, fatigue and stiffness by patient's Visual analogue scale (VAS) | The VAS score assessed by participants, is used to determine the symptom (pain, fatigue and stiffness) impact due to AS in the past week. The level is measured in millimeters (mm) on a 100 mm horizontal line. The score ranges from 0 (no pain) to 100 (severe pain). Data are presented as mean VAS score +/- standard deviation. | 6 weeks (at baseline, 2-weeks, 4-weeks, end of follow-up) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Individual evolution of intestinal Klebsiella | To compare the average change of Klebsiella bacteria, quantified in colony-forming unit per gram of feces (cfu/gr) in faecal samples among each participant. | 6 weeks (at baseline, 2-weeks, 4-weeks, end of follow-up) | 
| Change in Weight | To compare the average change in weight (kilograms) between LSD group and the controls, before and after the intervention. | 6 weeks (at baseline and the end of follow-up) | 
| Change in body mass index (BMI) | To compare the average change in BMI (kg/m2), calculated by weight/(height^2), between LSD group and the controls, before and after the intervention. | 6 weeks (at baseline and the end of follow-up) | 
| Change in body composition | To compare the average change in percentage of the evaluation of the body fat mass between LSD group and the controls, before and after the intervention. | 6 weeks (at baseline and the end of follow-up) | 
| Quantification of the average starch intake through 24h dietary recall | To quantify the average starch dietetic content (in grams per day), determined through the 24h dietetic recall applied for 3 days, to calculate the ingested starch during the intervention and determine the respective individual percentage of average reduction. | 6 weeks (3 days of each week till the end of follow-up) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Low Starch Diet (LSD), Klebsiella, Ankylosing Spondylitis, Disease activity, Quality of life, Nutrition, Diet therapy, Spondyloarthritis, Rheumatic Diseases, Spondylitis