Optimization of Anti-IL17 Antibody Therapy by Associating Fiber Supplementation to Correct Treatment-aggravated Gut Dysbiosis in Axial Spondyloarthritis - RESPOND-IL17
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 76
- 试验地点
- 6
- 主要终点
- Clostridial changes in the Experimental group
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
All treatments will be numbered. The treatment number will be assigned according to the randomization list. All participants (patient/evaluator/etc.) will be blinded to the treatment administered. Only the hospital pharmacy will know the assigned treatment and will guarantee the blinding.
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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))
排除标准
- •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
研究组 & 干预措施
Experimental group
Patients with aSp receiving fiber supplements in the form of Fibruline® Instant (Fagron laboratories)
干预措施: Daily dietary supplementation with Fibruline (Dietary Supplement)
Experimental group
Patients with aSp receiving fiber supplements in the form of Fibruline® Instant (Fagron laboratories)
干预措施: Anti-IL-17 therapy (Drug)
Control group
Patients with aSp receiving fake fiber supplements (placebo) in the form of Maltodextrine (laboratoire Fagron).
干预措施: Daily dietary supplementation with Fibruline (Dietary Supplement)
Control group
Patients with aSp receiving fake fiber supplements (placebo) in the form of Maltodextrine (laboratoire Fagron).
干预措施: Anti-IL-17 therapy (Drug)
结局指标
主要结局
Clostridial changes in the Experimental group
时间窗: Week 12
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.
Clostridial changes in Controls
时间窗: Week 12
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.
次要结局
- Urea in the experimental group(Month 12)
- Urea in the control group(Month 12)
- Effect at 12 weeks of placebo on clinical therapeutic response: Delta BASDAI(Week 12)
- Effect of placebo on clinical therapeutic response: GIQLI(Week 12)
- Tolerance of treatment in the control group(Month 3)
- Complete blood count: Red blood cells in the experimental group(Month 3)
- Bilirubin in the experimental group(Month 12)
- Bilirubin in the control group(Month 12)
- Effect of fiber supplementation on clinical therapeutic response in the experimental group: Delta BASDAI(Week 12)
- Effect of fiber supplementation on clinical therapeutic response in the experimental group: ASAS20(Week 12)
- Effect of fiber supplementation on clinical therapeutic response in the experimental group: ASAS40(Week 12)
- Effect of fiber supplementation on clinical therapeutic response in the experimental group: ASDAS(Week 12)
- Effect of fiber supplementation on clinical therapeutic response: GIQLI(Week 0)
- Effect of fiber supplmentation on clinical therapeutic response: GIQLI(Week 12)
- Effect at 12 weeks of placebo on clinical therapeutic response: ASA20(Week 12)
- Effect at 12 weeks of placebo on clinical therapeutic response: ASA40(Week 12)
- Effect at 12 weeks of placebo on clinical therapeutic response: ASDAS(Week 12)
- Tolerance of anti-IL17 intervention and treatment in the experimental group: Permeability(Month 0)
- Tolerance of anti-IL17 intervention and treatment in the experimental group(Month 3)
- Complete blood count: Hemoglobin in the experimental group(Month 3)
- Tolerance of anti-IL17 intervention and treatment in controls: Permeability(Month 3)
- Tolerance of anti-IL17 intervention and treatment in controls(Month 3)
- Presence of candida in patients in the experimental group(Month 3)
- Presence of candida in patients in the control group(Month 3)
- Tolerance of treatment in the experimental group(Month 3)
- Complete blood count: Hematocrit in the control group(Month 3)
- Complete blood count: Platelets in the experimental group(Month 3)
- Complete blood count: Red blood cells in the control group(Month 3)
- Complete blood count: White blood cells in the experimental group(Month 3)
- Complete blood count: White blood cells in the control group(Month 3)
- Complete blood count: Hemoglobin in the control group(Month 3)
- Complete blood count: Hematocrit in the experimental group(Month 3)
- Complete blood count: Platelets in the control group(Month 3)
- T-lymphocytes in the experimental group(Month 3)
- T-lymphocytes in the control group(Month 3)
- Monocytes in the experimental group(Month 3)
- Monocytes in the control group(Month 3)
- Aspartate aminotransferase (ASAT) in the experimental group(Month 3)
- Alanine aminotransferase (ALAT) in the experimental group(Month 3)
- Alanine aminotransferase (ALAT) in the control group(Month 3)
- Alkaline phosphatase in the experimental group(Month 3)
- Alkaline phosphatase in the control group(Month 3)
- Calcium in the experimental group(Month 3)
- Calcium in the control group(Month 3)
- Creatinine in the experimental group(Month 12)
- C-Reactive Protein in the experimental group(Month 12)
- Aspartate aminotransferase (ASAT) in the control group(Month 3)
- Creatinine in the control group(Month 12)
- Albumin in the experimental group(Month 12)
- Albumin in the control group(Month 12)
- C-Reactive Protein in the control group(Month 12)