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Symbiotics and Systemic Inflammation in Chronic Kidney Disease (SISMIC)

Primary Purpose

Chronic Renal Failure, Diabete Type 2, Systemic Inflammation

Status
Recruiting
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
probiotic Vivomixx®
prebiotic Orafti®Synergy1
Placebo
Sponsored by
Centre Hospitalier Universitaire de Besancon
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Renal Failure focused on measuring Inflammation, Chronic renal failure, Symbiotic

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • CHU de BesançonRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Symbiotic Treatment : probiotic Vivomixx® + prebiotic Orafti®Synergy1

Placebo

Arm Description

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.

Outcomes

Primary Outcome Measures

inflammation
change in inflammation estimated by the serum CRP concentration <6 mg / L

Secondary Outcome Measures

inflammatory cytokines 1
variation of IL-6
inflammatory cytokines 2
variation of IL-1β
inflammatory cytokines 3
variation of TNF-α
inflammatory cytokines 4
variation of IL-10
inflammatory cytokines 5
variation of IL-8
inflammatory cytokines 6
variation of IFNγ
inflammatory circulating monocytes
variation
intestinal microbial metabolome
modification of the intestinal microbial metabolome (Nuclear magnetic resonance)
intestinal membrane permeability
modification of LPS
bacterial translocation 1
modification of CD14s
bacterial translocation 2
modification of iFABP
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.
fragility
fragility (= 3 of the following 5 criteria: undernutrition, grip strength and walking speed, assessed exhaustion and physical activity)

Full Information

First Posted
September 4, 2020
Last Updated
August 1, 2022
Sponsor
Centre Hospitalier Universitaire de Besancon
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1. Study Identification

Unique Protocol Identification Number
NCT04769687
Brief Title
Symbiotics and Systemic Inflammation in Chronic Kidney Disease
Acronym
SISMIC
Official Title
Symbiotics and Systemic Inflammation in Chronic Kidney Disease
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 21, 2020 (Actual)
Primary Completion Date
May 1, 2023 (Anticipated)
Study Completion Date
November 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Hospitalier Universitaire de Besancon

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Renal Failure, Diabete Type 2, Systemic Inflammation
Keywords
Inflammation, Chronic renal failure, Symbiotic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Randomized, non-comparative 2: 1 phase 2 study (symbiotic vs placebo) aimed at evaluating the efficacy of the use of symbiotics in reducing chronic inflammation observed in chronic renal failure.
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
62 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Symbiotic Treatment : probiotic Vivomixx® + prebiotic Orafti®Synergy1
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Biological
Intervention Name(s)
probiotic Vivomixx®
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
prebiotic Orafti®Synergy1
Intervention Description
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).
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
inflammation
Description
change in inflammation estimated by the serum CRP concentration <6 mg / L
Time Frame
4 months
Secondary Outcome Measure Information:
Title
inflammatory cytokines 1
Description
variation of IL-6
Time Frame
At 2, 4 and 6 months after the start of treatment.
Title
inflammatory cytokines 2
Description
variation of IL-1β
Time Frame
At 2, 4 and 6 months after the start of treatment.
Title
inflammatory cytokines 3
Description
variation of TNF-α
Time Frame
At 2, 4 and 6 months after the start of treatment.
Title
inflammatory cytokines 4
Description
variation of IL-10
Time Frame
At 2, 4 and 6 months after the start of treatment.
Title
inflammatory cytokines 5
Description
variation of IL-8
Time Frame
At 2, 4 and 6 months after the start of treatment.
Title
inflammatory cytokines 6
Description
variation of IFNγ
Time Frame
At 2, 4 and 6 months after the start of treatment.
Title
inflammatory circulating monocytes
Description
variation
Time Frame
At 2, 4 and 6 months after the start of treatment.
Title
intestinal microbial metabolome
Description
modification of the intestinal microbial metabolome (Nuclear magnetic resonance)
Time Frame
At 2, 4 and 6 months after the start of treatment.
Title
intestinal membrane permeability
Description
modification of LPS
Time Frame
At 2, 4 and 6 months after the start of treatment.
Title
bacterial translocation 1
Description
modification of CD14s
Time Frame
At 2, 4 and 6 months after the start of treatment.
Title
bacterial translocation 2
Description
modification of iFABP
Time Frame
At 2, 4 and 6 months after the start of treatment.
Title
health-related quality of life
Description
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.
Time Frame
At 2, 4 and 6 months after the start of treatment.
Title
fragility
Description
fragility (= 3 of the following 5 criteria: undernutrition, grip strength and walking speed, assessed exhaustion and physical activity)
Time Frame
At 2, 4 and 6 months after the start of treatment.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
CHU de Besançon
City
Besançon
ZIP/Postal Code
25000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
GAIFFE Emilie
Phone
03 81 66 81 66
Ext
+33
Email
egaiffe@chu-besancon.fr

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Individual data can be provided on request after validation by the competent regulatory authorities.

Learn more about this trial

Symbiotics and Systemic Inflammation in Chronic Kidney Disease

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