Clinical trial NCT05812157: Optimizing Anti-IL17 Antibody Therapy by Associating Fiber Supplementation to Correct Treatment-aggravated Gut Dysbiosis in Axial Spondyloarthritis - RESPOND-IL17
Official title: Optimization of Anti-IL17 Antibody Therapy by Associating Fiber Supplementation to Correct Treatment-aggravated Gut Dysbiosis in Axial Spondyloarthritis - RESPOND-IL17
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Axial Spondyloarthritis
Keywords: dysbiosis
short-chain fatty acids
fiber
microbiota
Lead sponsor: Centre Hospitalier Universitaire de Nīmes
Sponsor class: OTHER
First posted: 2023-04-13
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter, double-blind, prospective, randomized controlled study
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion criteria:

* Patients with spondyloarthritis meeting the ASAS criteria
* Patient considered by the treating rheumatologist for anti-IL-17 biomedication
* Patients aged between 18 and 90 years of age
* Patients who are affiliated to a French social security system or beneficiaries of such a system
* Patients with no desire to become pregnant during the study period (Effective contraception for women of childbearing age during the study period (surgical sterilization, hormonal contraceptives, barrier method, intrauterine device))

Exclusion Criteria:

* Lack of written informed consent after a time of reflection
* Patients participating in other therapeutic research or having participated in research for which the exclusion period has not ended
* Patient under court protection, guardianship or curatorship.
* Patient unable to give consent.
* Pregnant or breastfeeding woman
* Patients with digestive disorders for which a chronic inflammatory bowel disease has not been excluded
* Patients with fructose intolerance or glucose or galactose malabsorption
* Patients with known intolerance to inulin or maltodextrin

Primary outcomes:
measure: Clostridial changes in the Experimental group
timeFrame: Week 0
measure: Clostridial changes in Controls
timeFrame: Week 0
measure: Clostridial changes in the Experimental group
timeFrame: Week 12
measure: Clostridial changes in Controls
timeFrame: Week 12
Secondary outcomes:
measure: Effect of fiber supplementation on clinical therapeutic response in the experimental group: Delta BASDAI
timeFrame: Week 0
measure: Effect of fiber supplementation on clinical therapeutic response in the experimental group: Delta BASDAI
timeFrame: Week 12
measure: Effect of fiber supplementation on clinical therapeutic response in the experimental group: ASAS20
timeFrame: Week 0
measure: Effect of fiber supplementation on clinical therapeutic response in the experimental group: ASAS20
timeFrame: Week 12
measure: Effect of fiber supplementation on clinical therapeutic response in the experimental group: ASAS40
timeFrame: Week 0
measure: Effect of fiber supplementation on clinical therapeutic response in the experimental group: ASAS40
timeFrame: Week 12
measure: Effect of fiber supplementation on clinical therapeutic response in the experimental group: ASDAS
timeFrame: Week 0
measure: Effect of fiber supplementation on clinical therapeutic response in the experimental group: ASDAS
timeFrame: Week 12
measure: Effect of fiber supplementation on clinical therapeutic response: GIQLI
timeFrame: Week 0
measure: Effect of fiber supplmentation on clinical therapeutic response: GIQLI
timeFrame: Week 12
measure: Effect at 12 weeks of placebo on clinical therapeutic response: Delta BASDAI
timeFrame: Week 0
measure: Effect at 12 weeks of placebo on clinical therapeutic response: Delta BASDAI
timeFrame: Week 12
measure: Effect at 12 weeks of placebo on clinical therapeutic response: ASA20
timeFrame: Week 0
measure: Effect at 12 weeks of placebo on clinical therapeutic response: ASA20
timeFrame: Week 12
measure: Effect at 12 weeks of placebo on clinical therapeutic response: ASA40
timeFrame: Week 0
measure: Effect at 12 weeks of placebo on clinical therapeutic response: ASA40
timeFrame: Week 12
measure: Effect at 12 weeks of placebo on clinical therapeutic response: ASDAS
timeFrame: Week 0
measure: Effect at 12 weeks of placebo on clinical therapeutic response: ASDAS
timeFrame: Week 12
measure: Effect of placebo on clinical therapeutic response: GIQLI
timeFrame: Week 0
measure: Effect of placebo on clinical therapeutic response: GIQLI
timeFrame: Week 12
measure: Tolerance of anti-IL17 intervention and treatment in the experimental group: Permeability
timeFrame: Month 0
measure: Tolerance of anti-IL17 intervention and treatment in controls: Permeability
timeFrame: Month 3
measure: Tolerance of anti-IL17 intervention and treatment in the experimental group
timeFrame: Month 3
measure: Tolerance of anti-IL17 intervention and treatment in controls
timeFrame: Month 3
measure: Presence of candida in patients in the experimental group
timeFrame: Month 3
measure: Presence of candida in patients in the control group
timeFrame: Month 3
measure: Tolerance of treatment in the experimental group
timeFrame: Month 3
measure: Tolerance of treatment in the control group
timeFrame: Month 3
measure: Complete blood count: Red blood cells in the experimental group
timeFrame: Month 0
measure: Complete blood count: Red blood cells in the control group
timeFrame: Month 0
measure: Complete blood count: Red blood cells in the experimental group
timeFrame: Month 3
measure: Complete blood count: Red blood cells in the control group
timeFrame: Month 3
measure: Complete blood count: White blood cells in the experimental group
timeFrame: Month 0
measure: Complete blood count: White blood cells in the control group
timeFrame: Month 0
measure: Complete blood count: White blood cells in the experimental group
timeFrame: Month 3
measure: Complete blood count: White blood cells in the control group
timeFrame: Month 3
measure: Complete blood count: Hemoglobin in the experimental group
timeFrame: Month 0
measure: Complete blood count: Hemoglobin in the control group
timeFrame: Month 0
measure: Complete blood count: Hemoglobin in the experimental group
timeFrame: Month 3
measure: Complete blood count: Hemoglobin in the control group
timeFrame: Month 3
measure: Complete blood count: Hematocrit in the experimental group
timeFrame: Month 0
measure: Complete blood count: Hematocrit in the control group
timeFrame: Month 0
measure: Complete blood count: Hematocrit in the experimental group
timeFrame: Month 3
measure: Complete blood count: Hematocrit in the control group
timeFrame: Month 3
measure: Complete blood count: Platelets in the experimental group
timeFrame: Month 0
measure: Complete blood count: Platelets in the control group
timeFrame: Month 0
measure: Complete blood count: Platelets in the experimental group
timeFrame: Month 3
measure: Complete blood count: Platelets in the control group
timeFrame: Month 3
measure: T-lymphocytes in the experimental group
timeFrame: Month 0
measure: T-lymphocytes in the control group
timeFrame: Month 0
measure: T-lymphocytes in the experimental group
timeFrame: Month 3
measure: T-lymphocytes in the control group
timeFrame: Month 3
measure: Monocytes in the experimental group
timeFrame: Month 0
measure: Monocytes in the control group
timeFrame: Month 0
measure: Monocytes in the experimental group
timeFrame: Month 3
measure: Monocytes in the control group
timeFrame: Month 3
measure: Aspartate aminotransferase (ASAT) in the experimental group
timeFrame: Month 0
measure: Aspartate aminotransferase (ASAT) in the experimental group
timeFrame: Month 3
measure: Aspartate aminotransferase (ASAT) in the control group
timeFrame: Month 0
measure: Aspartate aminotransferase (ASAT) in the control group
timeFrame: Month 3
measure: Alanine aminotransferase (ALAT) in the experimental group
timeFrame: Month 0
measure: Alanine aminotransferase (ALAT) in the experimental group
timeFrame: Month 3
measure: Alanine aminotransferase (ALAT) in the control group
timeFrame: Month 0
measure: Alanine aminotransferase (ALAT) in the control group
timeFrame: Month 3
measure: Alkaline phosphatase in the experimental group
timeFrame: Month 0
measure: Alkaline phosphatase in the experimental group
timeFrame: Month 3
measure: Alkaline phosphatase in the control group
timeFrame: Month 0
measure: Alkaline phosphatase in the control group
timeFrame: Month 3
measure: Calcium in the experimental group
timeFrame: Month 0
measure: Calcium in the experimental group
timeFrame: Month 3
measure: Calcium in the control group
timeFrame: Month 0
measure: Calcium in the control group
timeFrame: Month 3
measure: Creatinine in the experimental group
timeFrame: Month 0
measure: Creatinine in the experimental group
timeFrame: Month 12
measure: Creatinine in the control group
timeFrame: Month 0
measure: Creatinine in the control group
timeFrame: Month 12
measure: Albumin in the experimental group
timeFrame: Month 0
measure: Albumin in the experimental group
timeFrame: Month 12
measure: Albumin in the control group
timeFrame: Month 0
measure: Albumin in the control group
timeFrame: Month 12
measure: Urea in the experimental group
timeFrame: Month 0
measure: Urea in the experimental group
timeFrame: Month 12
measure: Urea in the control group
timeFrame: Month 0
measure: Urea in the control group
timeFrame: Month 12
measure: Bilirubin in the experimental group
timeFrame: Month 0
measure: Bilirubin in the experimental group
timeFrame: Month 12
measure: Bilirubin in the control group
timeFrame: Month 0
measure: Bilirubin in the control group
timeFrame: Month 12
measure: C-Reactive Protein in the experimental group
timeFrame: Month 0
measure: C-Reactive Protein in the experimental group
timeFrame: Month 12
measure: C-Reactive Protein in the control group
timeFrame: Month 0
measure: C-Reactive Protein in the control group
timeFrame: Month 12
Other outcomes:
Locations:
city: Nîmes
country: France
facility: Nîmes University Hospital
state: Gard
city: Montpellier
country: France
facility: Montpellier University Hospital
state: Hérault
city: Tours
country: France
facility: Tours Regional University Hospital (Bretonneau)
state: Indre-et-Loire
Study officials:
affiliation: Montpellier University Hospital
name: Cédric LUKAS, Professor
role: STUDY_DIRECTOR
affiliation: Montpellier University Hospital
name: Jacques MOREL, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Montpellier University Hospital
name: Claire DAIEN, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Montpellier University Hospital
name: Gaël MOUTERDE, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Nîmes University Hospital
name: Cécile GAUJOUX-VIALA, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Tours University Hospital
name: Denis MULLEMAN, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Tours University Hospital
name: Guillermo CARVAJAL, Doctor
role: PRINCIPAL_INVESTIGATOR
References: