Symbiotics and Systemic Inflammation in Chronic Kidney Disease (SISMIC)

Main objective: To assess the effectiveness of treatment with symbiotics on the chronic systemic inflammation observed in chronic renal failure 4 months after the start of treatment.

Study Overview

• Status: Recruiting
• Conditions: Chronic Renal Failure; Systemic Inflammation; Diabete Type 2
• Intervention / Treatment: Other: Placebo; Biological: probiotic Vivomixx®; Biological: prebiotic Orafti®Synergy1

Detailed Description

During a consultation in the nephrology departments : the study will be presented to the patient and the information leaflet will be given to him.

During a subsequent visit, after checking the level of serum CRP and obtaining the consent of the investigating physician, a blood test will be taken to assess the intestinal permeability and the inflammatory state. A health-related quality of life (SF-36) and frailty questionnaire (previous questionnaire, MNA questionnaire; Mini Nutritional Assessment - Short Form and physical activity question) will be completed by the patient. Two faecal sampling kits (one for D0 and one for M2) will be distributed to patients.

During the D0 visit, patients will be randomized into two arms. Both arms will receive the same dietary advice. The intervention group will receive symbiotics (prebiotics: Orafti®Synergy1 and probiotics: Vivomixx®) for 8 weeks against a placebo in the control group. The treatment will begin after the collection of the first stools (kit J0).

At the end of the treatment (M2 or 56 days later), a new blood sample will be taken. Two other blood samples will be taken 4 months and 6 months after the start of treatment. Patients will also provide a faecal sample and complete the various questionnaires at the end of treatment (M2), 2 months after (M4) and 4 months after (M6) treatment.

The study will have no influence on the management of the patient. It does not require any additional consultation or any particular biological assessment other than that described. Treatments should not be influenced by the study. The samples will be processed without knowledge of the initial characteristics of the patients, nor of their evolution.

• Study Type: Interventional
• Enrollment (Anticipated): 62
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Besançon, France, 25000
    • Recruiting
    • CHU de Besançon
    • Contact: GAIFFE Emilie; Phone Number: +33 03 81 66 81 66; Email: egaiffe@chu-besancon.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women aged 18 to 80 inclusive
• Women who have been menopausal for at least 24 months, surgically sterilized, or, for women of childbearing potential, use an effective method of contraception (oral contraceptives, contraceptive injections, intrauterine devices, double-barrier method, contraceptive patches)
• Signature of the informed consent to participate indicating that the subject has understood the purpose and the procedures required by the study and that he agrees to participate in the study and to comply with the requirements and restrictions inherent in this study
• Affiliation to a French social security scheme or beneficiary of such a scheme.
• Patient with type II diabetes
• Creatinine clearance less than 45 ml / min / 1.73m²
• Serum CRPus level greater than 6 mg / l, evaluated twice from 15 days to 3 months apart
• Patient not opposed to the conservation of biological samples for scientific research purposes.

Exclusion Criteria:

• Legal incapacity or limited legal capacity
• Subject unlikely to cooperate with the study and / or weak cooperation anticipated by the investigator
• Subject without health insurance
• Pregnant woman
• Subject being in the period of exclusion from another study or provided for by the "national file of volunteers".
• Infectious episode with need for hospitalization less than 1 month old.
• Active infection with hepatitis B and / or C virus.
• Active or non-progressive infection with HIV.
• Antibiotic therapy in the previous 3 months.
• Anti-inflammatory treatment.
• History of colectomy.
• All chronic digestive pathologies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Other: Placebo; Placebo
EXPERIMENTAL: Symbiotic Treatment : probiotic Vivomixx® + prebiotic Orafti®Synergy1; The prebiotic, Orafti®Synergy1, is made from a volume-to-volume mixture of oligofructoses and Raftiline HP. Orafti®Synergy1 is a slightly sweet white powder packaged in 5 g sachets that can be administered orally. The dose used is 2 sachets per day (morning and evening) for 8 weeks (56 days). The probiotic, Vivomixx®, consists of 4 strains of Lactobacillus (L. casei, L. plantarum, L. acidophilus and L. delbrueckii subsp. Bulgaricus) from 3 strains of Bifidobacterium (B. longum, B. breve, and B. infantis) and a strain of streptococcus (S. salivarius subsp thermophilus). Vivomixx® is in powder form packaged in sachets of 4.5.1011 bacteria which can be administered orally. The dose used is 2 sachets per day (morning and evening) for 8 weeks (56 days). For the study, the symbiotics will be packaged by the probiotic manufacturer in the same sachet (at the same doses as mentioned above) whether for the symbiotics or for the placebo.	Biological: probiotic Vivomixx®; Vivomixx® is in powder form packaged in sachets of 4.5.1011 bacteria. The dose used is 2 sachets per day (morning and evening) for 8 weeks (56 days). For the study, the symbiotics will be packaged in the same sachet at the same doses as mentioned above.; Biological: prebiotic Orafti®Synergy1; Orafti®Synergy1 is a slightly sweet white powder packaged in 5 g sachets. The dose used is 2 sachets per day (morning and evening) for 8 weeks (56 days).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
inflammation	change in inflammation estimated by the serum CRP concentration <6 mg / L	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
inflammatory cytokines 1	variation of IL-6	At 2, 4 and 6 months after the start of treatment.
inflammatory cytokines 2	variation of IL-1β	At 2, 4 and 6 months after the start of treatment.
inflammatory cytokines 3	variation of TNF-α	At 2, 4 and 6 months after the start of treatment.
inflammatory cytokines 4	variation of IL-10	At 2, 4 and 6 months after the start of treatment.
inflammatory cytokines 5	variation of IL-8	At 2, 4 and 6 months after the start of treatment.
inflammatory cytokines 6	variation of IFNγ	At 2, 4 and 6 months after the start of treatment.
inflammatory circulating monocytes	variation	At 2, 4 and 6 months after the start of treatment.
intestinal microbial metabolome	modification of the intestinal microbial metabolome (Nuclear magnetic resonance)	At 2, 4 and 6 months after the start of treatment.
intestinal membrane permeability	modification of LPS	At 2, 4 and 6 months after the start of treatment.
bacterial translocation 1	modification of CD14s	At 2, 4 and 6 months after the start of treatment.
bacterial translocation 2	modification of iFABP	At 2, 4 and 6 months after the start of treatment.
health-related quality of life	SF-36 Health Survey (Short Form) The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability.	At 2, 4 and 6 months after the start of treatment.
fragility	fragility (= 3 of the following 5 criteria: undernutrition, grip strength and walking speed, assessed exhaustion and physical activity)	At 2, 4 and 6 months after the start of treatment.

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Besancon

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 21, 2020
• Primary Completion (ANTICIPATED): May 1, 2023
• Study Completion (ANTICIPATED): November 1, 2023

Study Registration Dates

• First Submitted: September 4, 2020
• First Submitted That Met QC Criteria: February 22, 2021
• First Posted (ACTUAL): February 24, 2021

Study Record Updates

• Last Update Posted (ACTUAL): August 3, 2022
• Last Update Submitted That Met QC Criteria: August 1, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Inflammation; Chronic renal failure; Symbiotic
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Urologic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Kidney Diseases; Renal Insufficiency, Chronic; Inflammation; Kidney Failure, Chronic; Renal Insufficiency
• Other Study ID Numbers: API/2016/76 2019-A00850-57

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual data can be provided on request after validation by the competent regulatory authorities.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No