Fiber is the main source of energy for colonic bacteria and its consumption favorably modifies the composition of the microbiota in only a few days. Their fermentation in the colon releases short-chain fatty acids (SCFAs). Clostridiales contain many strains producing SCFAs. These SCFAs can restore the intestinal barrier and promote certain anti-inflammatory cells, including regulatory T cells (Tregs), which are essential to the mechanisms in tolerance of the self. Fibers could therefore correct the intestinal abnormalities present in patients with axial spondyloarthritis (AxSpA) and aggravated by anti-IL-17 drugs and thus improve the therapeutic response to these treatments. The hypothesis is that dietary fiber will correct the dysbiosis in AxSpA patients and increase the release of SCFAs, which favorably modulate the immune response and improve AxSpA.
Axial spondyloarthritis (AxSpA) is the second most common chronic inflammatory rheumatic disease, which develops preferentially in young subjects and results in a significant impairment of quality of life, particularly due to painful symptoms. The importance of the digestive system has long been recognized, since this disease is considered to be part of a larger group of diseases including Crohn's disease and ulcerative colitis because of their frequent association in the same patient, and because leaky gut disorders and alterations of the intestinal microbiota (dysbiosis) have been described in these patients. These abnormalities may stimulate the immune system and therefore be involved in inflammatory processes (especially Th17). The available treatments are based on non-steroidal anti-inflammatory drugs, and in the event of failure or intolerance, biomedicines targeting TNF can be used. Therapeutic monoclonal antibodies against IL-17 have recently enriched the therapeutic arsenal. Although most anti-TNF agents have a beneficial effect on the rheumatologic and digestive aspects of these diseases, anti-IL-17 agents are not expected to be effective in inflammatory bowel diseases. Indeed, a deleterious role of anti-IL-17 on the intestinal microbiota has even been demonstrated, which could result in a reduction of the systemic anti-inflammatory effect expected from these molecules, and consequently of the clinical benefit felt by the patient. In fact, anti-IL-17s lead to a significant decrease in Clostridiales, bacteria that participate in intestinal homeostasis. Fiber is the main source of energy for colonic bacteria and its consumption favorably modifies the composition of the microbiota in just a few days. Their fermentation in the colon releases short-chain fatty acids (SCFAs). Clostridiales contain many strains producing SCFAs. These SCFAs can restore the intestinal barrier and promote certain anti-inflammatory cells, including regulatory T cells (Tregs), which are essential to the mechanisms in tolerance of the self. Fibers could therefore correct the intestinal abnormalities present in AxSpA patients and aggravated by anti-IL-17 drugs and thus improve the therapeutic response to these treatments. The hypothesis is therefore that dietary fiber will correct the dysbiosis in AxSpA patients and increase the release of SCFAs, which favorably modulate the immune response and thus improve AxSpA.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
76
Supplementation with 12 grams per day of Fibruline reconstituted with 60mL of water, once a day
Patients in both groups will be on anti-IL-17 therapy
Nîmes University Hospital
Nîmes, Gard, France
Montpellier University Hospital
Montpellier, Hérault, France
Tours Regional University Hospital (Bretonneau)
Tours, Indre-et-Loire, France
Clostridial changes in the Experimental group
Patients will receive fiber supplementation with inulin (Fibruline® Instant, Fagron laboratory) at a rate of 12 grams of powder per day reconstituted with approximately 60mL of water and consumed in one intake per day. To confirm the efficacy of treatment, the percentage of patients with a \>10% decrease in Clostriadiales in their stools at 3 months after initiation of anti-IL-17 will be recorded. This percentage will be based on the distribution of bacteria analyzed by 16S RNA sequencing.
Time frame: Week 0
Clostridial changes in Controls
Patients will receive a placebo consisting of Maltodextrin (Fagron laboratories), packaged in jars identical to those used for inulin, with a volumetric equivalent, an energy contribution and very similar color. Patients will consume 12 grams of powder per day reconstituted with approximately 60mL of water and consumed in one intake per day. The percentage of patients with a \>10% decrease in Clostriadiales in their stools at 3 months after initiation of anti-IL-17 will be recorded. This percentage will be based on the distribution of bacteria analyzed by 16S RNA sequencing.
Time frame: Week 0
Clostridial changes in the Experimental group
Patients will receive fiber supplementation with inulin (Fibruline® Instant, Fagron laboratory) at a rate of 12 grams of powder per day reconstituted with approximately 60mL of water and consumed in one intake per day. To confirm the efficacy of treatment, the percentage of patients with a \>10% decrease in Clostriadiales in their stools at 3 months after initiation of anti-IL-17 will be recorded. This percentage will be based on the distribution of bacteria analyzed by 16S RNA sequencing.
Time frame: Week 12
Clostridial changes in Controls
Patients will receive a placebo consisting of Maltodextrin (Fagron laboratories), packaged in jars identical to those used for inulin, with a volumetric equivalent, an energy contribution and very similar color. Patients will consume 12 grams of powder per day reconstituted with approximately 60mL of water and consumed in one intake per day. The percentage of patients with a \>10% decrease in Clostriadiales in their stools at 3 months after initiation of anti-IL-17 will be recorded. This percentage will be based on the distribution of bacteria analyzed by 16S RNA sequencing.
Time frame: Week 12
Effect of fiber supplementation on clinical therapeutic response in the experimental group: Delta BASDAI
Clinical response rates observed in patients treated with anti-IL-17 with fiber supplementation will be recorded as a percentage. The BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) will be used to measure the percentage of patients responding positively to treatment.
Time frame: Week 0
Effect of fiber supplementation on clinical therapeutic response in the experimental group: Delta BASDAI
Clinical response rates observed at 3 months in patients treated with anti-IL-17 with fiber supplementation will be recorded as a percentage. The BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) will be used to measure the percentage of patients responding positively to treatment.
Time frame: Week 12
Effect of fiber supplementation on clinical therapeutic response in the experimental group: ASAS20
Clinical response rates observed in patients treated with anti-IL-17 with fiber supplementation will be recorded as a percentage. The ASAS20 will be used to measure the percentage of patients responding positively to treatment. This tool was developed by the Assessment of SpondylArthritis international Society (ASAS). The ASAS Response Criteria (ASAS 20) is defined as an improvement in at least 20% and an absolute improvement in at least 10 units on a 0-100 scale in at least three of the following domains: Patient global assessment, Pain assessment, Function, and Inflammation (last 2 questions of BASDAI).
Time frame: Week 0
Effect of fiber supplementation on clinical therapeutic response in the experimental group: ASAS20
Clinical response rates observed at 3 months in patients treated with anti-IL-17 with fiber supplementation will be recorded as a percentage. The ASAS20 will be used to measure the percentage of patients responding positively to treatment. This tool was developed by the Assessment of SpondylArthritis international Society (ASAS). The ASAS Response Criteria (ASAS 20) is defined as an improvement in at least 20% and an absolute improvement in at least 10 units on a 0-100 scale in at least three of the following domains: Patient global assessment, Pain assessment, Function, and Inflammation (last 2 questions of BASDAI).
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: Week 12
Effect of fiber supplementation on clinical therapeutic response in the experimental group: ASAS40
Clinical response rates observed in patients treated with anti-IL-17 with fiber supplementation will be recorded as a percentage. The ASAS40 will be used to measure the percentage of patients responding positively to treatment. This tool was developed by the Assessment of SpondylArthritis international Society (ASAS). The ASAS Response Criteria (ASAS 40) is defined as an improvement in at least 40% and an absolute improvement in at least 10 units on a 0-100 scale in at least three of the following domains: Patient global assessment, Pain assessment, Function, and Inflammation (last 2 questions of BASDAI).
Time frame: Week 0
Effect of fiber supplementation on clinical therapeutic response in the experimental group: ASAS40
Clinical response rates observed at 3 months in patients treated with anti-IL-17 with fiber supplementation will be recorded as a percentage. The ASAS40 will be used to measure the percentage of patients responding positively to treatment. This tool was developed by the Assessment of SpondylArthritis international Society (ASAS). The ASAS Response Criteria (ASAS 40) is defined as an improvement in at least 40% and an absolute improvement in at least 10 units on a 0-100 scale in at least three of the following domains: Patient global assessment, Pain assessment, Function, and Inflammation (last 2 questions of BASDAI).
Time frame: Week 12
Effect of fiber supplementation on clinical therapeutic response in the experimental group: ASDAS
Clinical response rates observed at 3 months in patients treated with anti-IL-17 with fiber supplementation will be recorded as a percentage. The ASDAS (Ankylosing Spondylitis Disease Activity Score) will be used to measure the percentage of patients responding positively to treatment. This tool is an index to assess disease activity in Ankylosing Spondylitis. The preferred score uses CRP (C-reactive protein) rather than ESR (erythrocyte sedimentation rate).
Time frame: Week 0
Effect of fiber supplementation on clinical therapeutic response in the experimental group: ASDAS
Clinical response rates observed at 3 months in patients treated with anti-IL-17 with fiber supplementation will be recorded as a percentage. The ASDAS (Ankylosing Spondylitis Disease Activity Score) will be used to measure the percentage of patients responding positively to treatment. This tool is an index to assess disease activity in Ankylosing Spondylitis. The preferred score uses CRP (C-reactive protein) rather than ESR (erythrocyte sedimentation rate).
Time frame: Week 12
Effect of fiber supplementation on clinical therapeutic response: GIQLI
Clinical response rates in patients treated with anti-IL-17 with fiber supplementation will be recorded as a percentage. Digestive symptoms will be assessed using the Gastrointestinal Quality of Life Index (GIQLI) questionnaire at Week 0 and Week 12. The GIQLI is a measure of the subjective perception of well-being by a patient, which may vary unexpectedly between diagnostic groups. The GIQLI was initiated in Germany and includes 36 items asking about symptoms, physical status, emotions, social dysfunction, and effects of medical treatment. The Questions cover the following 5 dimensions : symptoms, physical condition, emotions, social integration and medical treatment.
Time frame: Week 0
Effect of fiber supplmentation on clinical therapeutic response: GIQLI
Clinical response rates observed at 3 months in patients treated with anti-IL-17 with fiber supplementation will be recorded as a percentage. Digestive symptoms will be assessed using the Gastrointestinal Quality of Life Index (GIQLI) questionnaire at Week 0 and Week 12. The GIQLI is a measure of the subjective perception of well-being by a patient, which may vary unexpectedly between diagnostic groups. The GIQLI was initiated in Germany and includes 36 items asking about symptoms, physical status, emotions, social dysfunction, and effects of medical treatment. The Questions cover the following 5 dimensions : symptoms, physical condition, emotions, social integration and medical treatment.
Time frame: Week 12
Effect at 12 weeks of placebo on clinical therapeutic response: Delta BASDAI
Clinical response rates observed in patients treated with anti-IL-17 without fiber supplementation will be recorded as a percentage. The BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) will be used to measure the percentage of patients responding positively to treatment.
Time frame: Week 0
Effect at 12 weeks of placebo on clinical therapeutic response: Delta BASDAI
Clinical response rates observed at 3 months in patients treated with anti-IL-17 without fiber supplementation will be recorded as a percentage. The BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) will be used to measure the percentage of patients responding positively to treatment.
Time frame: Week 12
Effect at 12 weeks of placebo on clinical therapeutic response: ASA20
Clinical response rates observed in patients treated with anti-IL-17 without fiber supplementation will be recorded as a percentage. The ASAS20 will be used to measure the percentage of patients responding positively to treatment.This tool was developed by the Assessment of SpondylArthritis international Society (ASAS). The ASAS Response Criteria (ASAS 20) is defined as an improvement in at least 20% and an absolute improvement in at least 10 units on a 0-100 scale in at least three of the following domains: Patient global assessment, Pain assessment, Function, and Inflammation (last 2 questions of BASDAI).
Time frame: Week 0
Effect at 12 weeks of placebo on clinical therapeutic response: ASA20
Clinical response rates observed at 3 months in patients treated with anti-IL-17 without fiber supplementation will be recorded as a percentage. The ASAS20 will be used to measure the percentage of patients responding positively to treatment.This tool was developed by the Assessment of SpondylArthritis international Society (ASAS). The ASAS Response Criteria (ASAS 20) is defined as an improvement in at least 20% and an absolute improvement in at least 10 units on a 0-100 scale in at least three of the following domains: Patient global assessment, Pain assessment, Function, and Inflammation (last 2 questions of BASDAI).
Time frame: Week 12
Effect at 12 weeks of placebo on clinical therapeutic response: ASA40
Clinical response rates observed in patients treated with anti-IL-17 without fiber supplementation will be recorded as a percentage. The ASAS40 will be used to measure the percentage of patients responding positively to treatment.This tool was developed by the Assessment of SpondylArthritis international Society (ASAS). The ASAS Response Criteria (ASAS 40) is defined as an improvement in at least 40% and an absolute improvement in at least 10 units on a 0-100 scale in at least three of the following domains: Patient global assessment, Pain assessment, Function, and Inflammation (last 2 questions of BASDAI).
Time frame: Week 0
Effect at 12 weeks of placebo on clinical therapeutic response: ASA40
Clinical response rates observed at 3 months in patients treated with anti-IL-17 without fiber supplementation will be recorded as a percentage. The ASAS40 will be used to measure the percentage of patients responding positively to treatment.This tool was developed by the Assessment of SpondylArthritis international Society (ASAS). The ASAS Response Criteria (ASAS 40) is defined as an improvement in at least 40% and an absolute improvement in at least 10 units on a 0-100 scale in at least three of the following domains: Patient global assessment, Pain assessment, Function, and Inflammation (last 2 questions of BASDAI).
Time frame: Week 12
Effect at 12 weeks of placebo on clinical therapeutic response: ASDAS
Clinical response rates observed at 3 months in patients treated with anti-IL-17 without fiber supplementation will be recorded as a percentage. The ASDAS (Ankylosing Spondylitis Disease Activity Score) will be used to measure the percentage of patients responding positively to treatment. This tool is an index to assess disease activity in Ankylosing Spondylitis. The preferred score uses CRP (C-reactive protein) rather than ESR (erythrocyte sedimentation rate).
Time frame: Week 0
Effect at 12 weeks of placebo on clinical therapeutic response: ASDAS
Clinical response rates observed at 3 months in patients treated with anti-IL-17 without fiber supplementation will be recorded as a percentage. The ASDAS (Ankylosing Spondylitis Disease Activity Score) will be used to measure the percentage of patients responding positively to treatment. This tool is an index to assess disease activity in Ankylosing Spondylitis. The preferred score uses CRP (C-reactive protein) rather than ESR (erythrocyte sedimentation rate).
Time frame: Week 12
Effect of placebo on clinical therapeutic response: GIQLI
Clinical response rates observed in patients treated with anti-IL-17 without fiber supplementation will be recorded as a percentage. Digestive symptoms will be assessed using the Gastrointestinal Quality of Life Index (GIQLI) questionnaire at Week 0 and Week 12. The GIQLI is a measure of the subjective perception of well-being by a patient, which may vary unexpectedly between diagnostic groups. The GIQLI was initiated in Germany and includes 36 items asking about symptoms, physical status, emotions, social dysfunction, and effects of medical treatment. The Questions cover the following 5 dimensions : symptoms, physical condition, emotions, social integration and medical treatment.
Time frame: Week 0
Effect of placebo on clinical therapeutic response: GIQLI
Clinical response rates observed at 3 months in patients treated with anti-IL-17 without fiber supplementation will be recorded as a percentage. Digestive symptoms will be assessed using the Gastrointestinal Quality of Life Index (GIQLI) questionnaire at Week 0 and Week 12. The GIQLI is a measure of the subjective perception of well-being by a patient, which may vary unexpectedly between diagnostic groups. The GIQLI was initiated in Germany and includes 36 items asking about symptoms, physical status, emotions, social dysfunction, and effects of medical treatment. The Questions cover the following 5 dimensions : symptoms, physical condition, emotions, social integration and medical treatment.
Time frame: Week 12
Tolerance of anti-IL17 intervention and treatment in the experimental group: Permeability
Changes in serum concentrations of intestinal permeability markers (zonulin, claudin-3, iFABP); and endotoxemia (LBP, CD14s) will be measured by ELISA in ng/ml
Time frame: Month 0
Tolerance of anti-IL17 intervention and treatment in controls: Permeability
Changes in serum concentrations of intestinal permeability markers (zonulin, claudin-3, iFABP); and endotoxemia (LBP, CD14s) will be measured by ELISA in ng/ml
Time frame: Month 3
Tolerance of anti-IL17 intervention and treatment in the experimental group
The distribution and diversity of different germs will be measured by 16S RNA sequencing. Quantitative
Time frame: Month 3
Tolerance of anti-IL17 intervention and treatment in controls
The distribution and diversity of different germs will be measured by 16S RNA sequencing. Quantitative
Time frame: Month 3
Presence of candida in patients in the experimental group
YES/NO
Time frame: Month 3
Presence of candida in patients in the control group
YES/NO
Time frame: Month 3
Tolerance of treatment in the experimental group
All adverse events related or not to anti-IL17 treatment and potentially associated with the consumption of high doses of fiber (bloating, flatulence, diarrhea, abdominal pain) will be recorded
Time frame: Month 3
Tolerance of treatment in the control group
All adverse events related or not to anti-IL17 treatment and potentially associated with the consumption of high doses of fiber (bloating, flatulence, diarrhea, abdominal pain) will be recorded
Time frame: Month 3
Complete blood count: Red blood cells in the experimental group
Red blood cells will be measured in millions/mm3
Time frame: Month 0
Complete blood count: Red blood cells in the control group
Red blood cells will be measured in millions/mm3
Time frame: Month 0
Complete blood count: Red blood cells in the experimental group
Red blood cells will be measured in millions/mm3
Time frame: Month 3
Complete blood count: Red blood cells in the control group
Red blood cells will be measured in millions/mm3
Time frame: Month 3
Complete blood count: White blood cells in the experimental group
White blood cells will be measured in millions/mm3
Time frame: Month 0
Complete blood count: White blood cells in the control group
White blood cells will be measured in millions/mm3
Time frame: Month 0
Complete blood count: White blood cells in the experimental group
White blood cells will be measured in millions/mm3
Time frame: Month 3
Complete blood count: White blood cells in the control group
White blood cells will be measured in millions/mm3
Time frame: Month 3
Complete blood count: Hemoglobin in the experimental group
Hemoglobin will be measured in g/L
Time frame: Month 0
Complete blood count: Hemoglobin in the control group
Hemoglobin will be measured in g/L
Time frame: Month 0
Complete blood count: Hemoglobin in the experimental group
Hemoglobin will be measured in g/L
Time frame: Month 3
Complete blood count: Hemoglobin in the control group
Hemoglobin will be measured in g/L
Time frame: Month 3
Complete blood count: Hematocrit in the experimental group
Hematocrit will be measured as a % of whole blood
Time frame: Month 0
Complete blood count: Hematocrit in the control group
Hematocrit will be measured as a % of whole blood
Time frame: Month 0
Complete blood count: Hematocrit in the experimental group
Hematocrit will be measured as a % of whole blood
Time frame: Month 3
Complete blood count: Hematocrit in the control group
Hematocrit will be measured as a % of whole blood
Time frame: Month 3
Complete blood count: Platelets in the experimental group
Platelets will be measured in K/µL
Time frame: Month 0
Complete blood count: Platelets in the control group
Platelets will be measured in K/µL
Time frame: Month 0
Complete blood count: Platelets in the experimental group
Platelets will be measured in K/µL
Time frame: Month 3
Complete blood count: Platelets in the control group
Platelets will be measured in K/µL
Time frame: Month 3
T-lymphocytes in the experimental group
The phenotype of T-lymphocytes (Treg, Thelpers) will be measured as % of total white blood cells
Time frame: Month 0
T-lymphocytes in the control group
The phenotype of T-lymphocytes (Treg, Thelpers) will be measured as % of total white blood cells
Time frame: Month 0
T-lymphocytes in the experimental group
The phenotype of T-lymphocytes (Treg, Thelpers) will be measured as % of total white blood cells
Time frame: Month 3
T-lymphocytes in the control group
The phenotype of T-lymphocytes (Treg, Thelpers) will be measured as % of total white blood cells
Time frame: Month 3
Monocytes in the experimental group
Monocytes will be measured by flow cytometry (CD25, CD127, CXCR3, CCR6, CD294, CD14, CD16, TNF, IL-6) as % of total white blood cells
Time frame: Month 0
Monocytes in the control group
Monocytes will be measured by flow cytometry (CD25, CD127, CXCR3, CCR6, CD294, CD14, CD16, TNF, IL-6) as % of total white blood cells
Time frame: Month 0
Monocytes in the experimental group
Monocytes will be measured by flow cytometry (CD25, CD127, CXCR3, CCR6, CD294, CD14, CD16, TNF, IL-6) as % of total white blood cells
Time frame: Month 3
Monocytes in the control group
Monocytes will be measured by flow cytometry (CD25, CD127, CXCR3, CCR6, CD294, CD14, CD16, TNF, IL-6) as % of total white blood cells
Time frame: Month 3
Aspartate aminotransferase (ASAT) in the experimental group
Aspartate aminotransferase (or ASAT) will be measured in international units per liter
Time frame: Month 0
Aspartate aminotransferase (ASAT) in the experimental group
Aspartate aminotransferase (or ASAT) will be measured in international units per liter
Time frame: Month 3
Aspartate aminotransferase (ASAT) in the control group
Aspartate aminotransferase (or ASAT) will be measured in international units per liter
Time frame: Month 0
Aspartate aminotransferase (ASAT) in the control group
Aspartate aminotransferase (or ASAT) will be measured in international units per liter
Time frame: Month 3
Alanine aminotransferase (ALAT) in the experimental group
Alanine aminotransferase (ALAT) will be measured in international units per liter
Time frame: Month 0
Alanine aminotransferase (ALAT) in the experimental group
Alanine aminotransferase (ALAT) will be measured in international units per liter
Time frame: Month 3
Alanine aminotransferase (ALAT) in the control group
Alanine aminotransferase (ALAT) will be measured in international units per liter
Time frame: Month 0
Alanine aminotransferase (ALAT) in the control group
Alanine aminotransferase (ALAT) will be measured in international units per liter
Time frame: Month 3
Alkaline phosphatase in the experimental group
Alkaline phosphatase (ALP) will be measured in units per liter
Time frame: Month 0
Alkaline phosphatase in the experimental group
Alkaline phosphatase (ALP) will be measured in units per liter
Time frame: Month 3
Alkaline phosphatase in the control group
Alkaline phosphatase (ALP) will be measured in units per liter
Time frame: Month 0
Alkaline phosphatase in the control group
Alkaline phosphatase (ALP) will be measured in units per liter
Time frame: Month 3
Calcium in the experimental group
Calcium will be measured in mmol/L
Time frame: Month 0
Calcium in the experimental group
Calcium will be measured in mmol/L
Time frame: Month 3
Calcium in the control group
Calcium will be measured in mmol/L
Time frame: Month 0
Calcium in the control group
Calcium will be measured in mmol/L
Time frame: Month 3
Creatinine in the experimental group
Calcium will be measured in μmol/L
Time frame: Month 0
Creatinine in the experimental group
Calcium will be measured in μmol/L
Time frame: Month 12
Creatinine in the control group
Calcium will be measured in μmol/L
Time frame: Month 0
Creatinine in the control group
Calcium will be measured in μmol/L
Time frame: Month 12
Albumin in the experimental group
Albumin will be measured in g/liter
Time frame: Month 0
Albumin in the experimental group
Albumin will be measured in g/liter
Time frame: Month 12
Albumin in the control group
Albumin will be measured in g/liter
Time frame: Month 0
Albumin in the control group
Albumin will be measured in g/liter
Time frame: Month 12
Urea in the experimental group
Urea will be measured in mmol/L
Time frame: Month 0
Urea in the experimental group
Urea will be measured in mmol/L
Time frame: Month 12
Urea in the control group
Urea will be measured in mmol/L
Time frame: Month 0
Urea in the control group
Urea will be measured in mmol/L
Time frame: Month 12
Bilirubin in the experimental group
Bilirubin will be measured in µmol/L
Time frame: Month 0
Bilirubin in the experimental group
Bilirubin will be measured in µmol/L
Time frame: Month 12
Bilirubin in the control group
Bilirubin will be measured in µmol/L
Time frame: Month 0
Bilirubin in the control group
Bilirubin will be measured in µmol/L
Time frame: Month 12
C-Reactive Protein in the experimental group
C-Reactive Protein will be measured in mg/L
Time frame: Month 0
C-Reactive Protein in the experimental group
C-Reactive Protein will be measured in mg/L
Time frame: Month 12
C-Reactive Protein in the control group
C-Reactive Protein will be measured in mg/L
Time frame: Month 0
C-Reactive Protein in the control group
C-Reactive Protein will be measured in mg/L
Time frame: Month 12