End Stage Renal DiseaseNCT03066921
Evaluation Of The Efficacy of a Strain-Specific Probiotic Formulation in Hemodialysis Patients
A study testing Probiotic packet in people with End Stage Renal Disease, run by Paik Seong Lim at 1 site in Taiwan.
Trial summary
Previous studies found that lactic acid bacteria could inhibit the activity of the performance of aristolochic acids (AAs) and improve apoptosis of proximal tubular epithelial cells (NRK-52E) and renal fibrosis on rats. Read more about this study
- Who is it for?
- Ages 20 to 75 years
- Conditions the study is for
- End Stage Renal Disease
- What is being tested?
- Probiotic packet
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 52 participants
- Where
- 1 siteTaiwan
- Study dates
- Jun 2016to Dec 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Both sexes aged between 20-75 years.
- Received stable hemodialysis at least 3 months.
- Written informed consent.
Who cannot join
- patients with severe infections, severe heart disease and liver disease, malignancy, autoimmune disorders, severe malnutrition, or clinical conditions requiring oral nutrition supplements;
- Inability to follow protocol.
- patients with known gastro-intestinal disease (i.e.,inflammatory bowel disease,crohn's disease,ulcerative colitis)
- Use of antibiotics, prebiotics or probiotics and immunosuppression medications in the past 4 weeks
- Pregnancy or wishing/trying to get pregnant
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation of the Effects of a Probiotic Formulation in Hemodialysis Patients
Previous studies found that lactic acid bacteria could inhibit the activity of the performance of aristolochic acids (AAs) and improve apoptosis of proximal tubular epithelial cells (NRK-52E) and renal fibrosis on rats. The aim of this study is to assessment a novel health food of lactic acid bacteria for preventing renal dysfunction and replacing or assisting conventional drug treatment. This study in 300 hemodialysis patients with dialysis quality assessment index (KT/V, urea reduction ratio (URR), albumin, prealbumin, Hb, CRP…) screened for more than three months, and the stability of the situation in dialysis patients. They will be divided into two groups in order to conduct ergonomic assessments. One group maintains their original diet and medicine. The other group will take the novel lactic acid bacteria and placebo (1x1011 cfu/3±0.2 g/bag) in every morning and evening after their meals. The effect of 0, 6, 12, 18, 24 weeks of the novel lactic acid bacteria will be assessed after starvation for 4 weeks. Group C was the control group did not give any test samples, but continued to observe. The overall goal of the aforementioned study is to develop a novel food product of lactic acid bacteria which can improve dialysis quality for hemodialysis patients. The investigators hope that this novel product can get a patent and be commercialized.
Read the detailed description
Background:
Insulin resistance (IR) and its associated metabolic disorders are common features of chronic kidney disease (CKD)and accumulating evidence suggested they are important contributors for the cardiovascular burden of CKD patients. In recent years, the modification of the intestinal flora and activation of inflammation pathways have been implicated in the pathogenesis of IR in patients suffering from metabolic syndrome. These important discoveries have led to major advances in understanding the mechanisms of uraemia-induced IR. Furthermore, recent studies show impairment of the intestinal barrier and renal function function as well as changes in the composition of the gut microbiome can contribute to the prevailing inflammation, and gut-derived uremic toxins. Some of these uraemic toxins have been linked to the pathogenesis of IR.
Probiotics is one of the functional foods believed to mediate their health promoting activities through modulating the composition of the gut health. Ingestion of probiotics has been shown not only to influence gut microbiota composition but also the secretion of the gut hormones that ameliorate insulin resistance in animal models. Limited trials in human also showed that supplementation with probiotic not only affect glucose homeostasis, but improved other diabetes related comorbidities such as metabolic syndrome, hypertension, and hyperlipidemia. It also increasing clear that many of the multifactorial physiological functions of gut bacteria are highly strain specific, preselection of appropriate probiotic strains based on their expression of functional biomarkers is critical
Objectives and hypotheses:
To address this research gap, this randomized controlled trial is proposed to determine the efficacy of probiotic formulation to improve metabolic profile and reduction of uremic toxins through modulating gut microbiota composition and gut immune function in hemodialysis patients.The investigators hypothesized that the probiotic supplementations will improve blood glucose control as well as other related metabolic aberrations and lower the levels of gut-derived uremic toxins.
Methodology:
This is a single center, double blind randomized parallel group control trial with 6 months probiotic formulation with strain specific lactobacillus or placebo. After screening the eligible subjects will be selected. Then, after consent taking and 4 weeks of washout period, participants will be randomly assigned to either receive probiotic formulation or placebo for 6 months. Measurements of blood parameters including glycemic control related parameters, lipid profile, nutritional markers, inflammatory markers and uremic toxins. Nutritional assessments, quality of life assessment and anthropometry measurements will take place at baseline, and after 24 months.
- Conditions
- End Stage Renal Disease
- Being tested
- Probiotic packet, Placebo
- Keywords
- Lactic acid bacteria, dyslipidemia uremic toxins, Hemodialysis
- Medical subject headings
- Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Probiotic packetDietary supplement
Probiotic formulation will be given at a dose of one packet thrice daily for 24 weeks, amounting to a total of 300 billion colony forming units(CFU)/day. Each packet contains 100 billion viable lyophilized bacteria of three strains of Lactobacillus viz Lactococcus lactis subsp. Lactis LL358 (BCRC910699)、Lactobacillus salivarius LS159 (BCRC910700) and Lactobacillus pentosus and excipients.
PlaceboDietary supplement
Placebo packet will be given at a dose of one sachet thrice daily for 24 weeks; Placebo packet contain all excipients as present in packets (without the 3 strains of bacteria as mentioned above).
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo packet will be given at a dose of one sachet thrice daily for 24 weeks; Placebo packet contain all excipients as present in packets (without the 3 strains of bacteria as mentioned above). Receives: Dietary Supplement: Placebo |
| Probiotic packet | Experimental | Probiotic formulation will be given at a dose of one packet thrice daily for 24 weeks, amounting to a total of 300 billion colony forming units(CFU)/day. Each packet contains 100 billion viable lyophilized bacteria of three strains of Lactobacillus viz Lactococcus lactis subsp. Lactis LL358 (BCRC910699)、Lactobacillus salivarius LS159 (BCRC910700) and Lactobacillus pentosus and excipients. Receives: Dietary Supplement: Probiotic packet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from Baseline Triglyceride/HDL cholesterol ratio at 3 months, 6 months and 3 months after the trial
Plasma triglycerides are measured by enzymatic methods. High-density lipoprotein (HDL) cholesterol is measured in the supernatant after sodium phosphotungstate/magnesium chloride precipitation.
Measured: baseline,3 months, 6 months and 3 months after the trial
Secondary outcomes (6)
Plasma concentrations of typical gut-derived uremic toxins(Indoxyl sulfate and p-cresyl sulfate)
All uremic toxins are measured by a high performance liquid chromatography method and fluorescence detection method.
Measured: baseline,3 months, 6 months and 3 months after the trial
plasma concentrations of inflammatory biomarkers
Interleukin-6 (IL-6) level is measured by an immunoenzymatic method, and C reactive protein (CRP) levels is measured by an immunonephelometric method.
Measured: baseline,3 months, 6 months and 3 months after the trial
plasma concentrations of microbial translocation biomarkers
LBP and sCD14 are measured using an enzyme-linked immunosorbent assay (ELISA).
Measured: baseline,3 months, 6 months and 3 months after the trial
Quality of life
Assessed with the Medical Outcomes Study Short Form 36-Item Health Survey (SF-36)
Measured: baseline and 6 months
Nutritional Status
Assessment with Subjective Global Assesment(SGA) and Mini Nutritional Assessment (MNA)
Measured: baseline and 6 months
Gut function questionnaire as a measure of tolerability
Questionnaire is used to assess the tolerability of the probiotic supplementation. Questionnaire includes questions on frequency and severity of flatulence and bloating, occurrence of diarrhea, frequency of defecation, and texture of feces using a stool chart.
Measured: Symptoms during first month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2017
- Study startJun 2016
- Primary completionOct 2017
- Study completionDec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for End Stage Renal DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized placebo controlled trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Paik Seong Lim
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Paik Seong Lim, Tungs' Taichung Metroharbour Hospital
- Investigators
- Paik Seong Lim, PhD, Principal investigator, Tungs' Taichung Metroharbour Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03066921
- Sponsor's protocol ID
- 104012
- Status last verified
- Jan 2018
- First submitted
- 20 Feb 2017
- Last updated
- 11 Jan 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lim PS, Wang HF, Lee MC, Chiu LS, Wu MY, Chang WC, Wu TK. The Efficacy of Lactobacillus-Containing Probiotic Supplementation in Hemodialysis Patients: A Randomized, Double-Blind, Placebo-Controlled Trial. J Ren Nutr. 2021 Mar;31(2):189-198. doi: 10.1053/j.jrn.2020.07.002. Epub 2020 Sep 6.
PubMed 32900583
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Effects of a Probiotic Formulation in Hemodialysis Patients
- ClinicalTrials.gov ID
- NCT03066921
- Acronym / sponsor ID
- 104012
- Conditions
- End Stage Renal Disease
- Keywords
- Lactic acid bacteria, dyslipidemia uremic toxins, Hemodialysis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Paik Seong LimUniversity, hospital or other
- Study start
- Jun 2016 (actual)
- Primary completion
- Oct 2017 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 1 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Previous studies found that lactic acid bacteria could inhibit the activity of the performance of aristolochic acids (AAs) and improve apoptosis of proximal tubular epithelial cells (NRK-52E) and renal fibrosis on rats. The aim of this study is to assessment a novel health food of lactic acid bacteria for preventing renal dysfunction and replacing or assisting conventional drug treatment. This study in 300 hemodialysis patients with dialysis quality assessment index (KT/V, urea reduction ratio (URR), albumin, prealbumin, Hb, CRP…) screened for more than three months, and the stability of the situation in dialysis patients. They will be divided into two groups in order to conduct ergonomic assessments. One group maintains their original diet and medicine. The other group will take the novel lactic acid bacteria and placebo (1x1011 cfu/3±0.2 g/bag) in every morning and evening after their meals. The effect of 0, 6, 12, 18, 24 weeks of the novel lactic acid bacteria will be assessed after starvation for 4 weeks. Group C was the control group did not give any test samples, but continued to observe. The overall goal of the aforementioned study is to develop a novel food product of lactic acid bacteria which can improve dialysis quality for hemodialysis patients. The investigators hope that this novel product can get a patent and be commercialized.
Detailed description
Background:
Insulin resistance (IR) and its associated metabolic disorders are common features of chronic kidney disease (CKD)and accumulating evidence suggested they are important contributors for the cardiovascular burden of CKD patients. In recent years, the modification of the intestinal flora and activation of inflammation pathways have been implicated in the pathogenesis of IR in patients suffering from metabolic syndrome. These important discoveries have led to major advances in understanding the mechanisms of uraemia-induced IR. Furthermore, recent studies show impairment of the intestinal barrier and renal function function as well as changes in the composition of the gut microbiome can contribute to the prevailing inflammation, and gut-derived uremic toxins. Some of these uraemic toxins have been linked to the pathogenesis of IR.
Probiotics is one of the functional foods believed to mediate their health promoting activities through modulating the composition of the gut health. Ingestion of probiotics has been shown not only to influence gut microbiota composition but also the secretion of the gut hormones that ameliorate insulin resistance in animal models. Limited trials in human also showed that supplementation with probiotic not only affect glucose homeostasis, but improved other diabetes related comorbidities such as metabolic syndrome, hypertension, and hyperlipidemia. It also increasing clear that many of the multifactorial physiological functions of gut bacteria are highly strain specific, preselection of appropriate probiotic strains based on their expression of functional biomarkers is critical
Objectives and hypotheses:
To address this research gap, this randomized controlled trial is proposed to determine the efficacy of probiotic formulation to improve metabolic profile and reduction of uremic toxins through modulating gut microbiota composition and gut immune function in hemodialysis patients.The investigators hypothesized that the probiotic supplementations will improve blood glucose control as well as other related metabolic aberrations and lower the levels of gut-derived uremic toxins.
Methodology:
This is a single center, double blind randomized parallel group control trial with 6 months probiotic formulation with strain specific lactobacillus or placebo. After screening the eligible subjects will be selected. Then, after consent taking and 4 weeks of washout period, participants will be randomly assigned to either receive probiotic formulation or placebo for 6 months. Measurements of blood parameters including glycemic control related parameters, lipid profile, nutritional markers, inflammatory markers and uremic toxins. Nutritional assessments, quality of life assessment and anthropometry measurements will take place at baseline, and after 24 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized placebo controlled trial
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Dietary Supplement: PlaceboPlacebo packet will be given at a dose of one sachet thrice daily for 24 weeks; Placebo packet contain all excipients as present in packets (without the 3 strains of bacteria as mentioned above). |
| Probiotic packet | Experimental | Dietary Supplement: Probiotic packetProbiotic formulation will be given at a dose of one packet thrice daily for 24 weeks, amounting to a total of 300 billion colony forming units(CFU)/day. Each packet contains 100 billion viable lyophilized bacteria of three strains of Lactobacillus viz Lactococcus lactis subsp. Lactis LL358 (BCRC910699)、Lactobacillus salivarius LS159 (BCRC910700) and Lactobacillus pentosus and excipients. |
Who may qualify
- Ages
- 20 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Both sexes aged between 20-75 years.
- Received stable hemodialysis at least 3 months.
- Written informed consent.
Key exclusion criteria (5 listed)
- patients with severe infections, severe heart disease and liver disease, malignancy, autoimmune disorders, severe malnutrition, or clinical conditions requiring oral nutrition supplements;
- Inability to follow protocol.
- patients with known gastro-intestinal disease (i.e.,inflammatory bowel disease,crohn's disease,ulcerative colitis)
- Use of antibiotics, prebiotics or probiotics and immunosuppression medications in the past 4 weeks
- Pregnancy or wishing/trying to get pregnant
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Probiotic packetProbiotic formulation will be given at a dose of one packet thrice daily for 24 weeks, amounting to a total of 300 billion colony forming units(CFU)/day. Each packet contains 100 billion viable lyophilized bacteria of three strains of Lactobacillus viz Lactococcus lactis subsp. Lactis LL358 (BCRC910699)、Lactobacillus salivarius LS159 (BCRC910700) and Lactobacillus pentosus and excipients. | Dietary supplement | Probiotic packet |
| PlaceboPlacebo packet will be given at a dose of one sachet thrice daily for 24 weeks; Placebo packet contain all excipients as present in packets (without the 3 strains of bacteria as mentioned above). | Dietary supplement | Placebo |
Primary outcome
Change from Baseline Triglyceride/HDL cholesterol ratio at 3 months, 6 months and 3 months after the trial
Time frame: baseline,3 months, 6 months and 3 months after the trial
Plasma triglycerides are measured by enzymatic methods. High-density lipoprotein (HDL) cholesterol is measured in the supernatant after sodium phosphotungstate/magnesium chloride precipitation.
6 secondary outcomes
Plasma concentrations of typical gut-derived uremic toxins(Indoxyl sulfate and p-cresyl sulfate)
Time frame: baseline,3 months, 6 months and 3 months after the trial
plasma concentrations of inflammatory biomarkers
Time frame: baseline,3 months, 6 months and 3 months after the trial
plasma concentrations of microbial translocation biomarkers
Time frame: baseline,3 months, 6 months and 3 months after the trial
Quality of life
Time frame: baseline and 6 months
Nutritional Status
Time frame: baseline and 6 months
Gut function questionnaire as a measure of tolerability
Time frame: Symptoms during first month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2018.
- Derived from this study: PubMed 32900583Lim PS, Wang HF, Lee MC, Chiu LS, Wu MY, Chang WC, Wu TK. The Efficacy of Lactobacillus-Containing Probiotic Supplementation in Hemodialysis Patients: A Randomized, Double-Blind, Placebo-Controlled Trial. J Ren Nutr. 2021 Mar;31(2):189-198. doi: 10.1053/j.jrn.2020.07.002. Epub 2020 Sep 6.
- Individual participant dataSharing planned: No
Related trials for End Stage Renal Disease
Active, not recruitingPhase 2
Safety and Efficacy of Empagliflozin in Hemodialysis
End Stage Renal Disease
Not yet recruiting
Hypothermic Kidney Machine Perfusion With Omnisol
End Stage Renal Disease (ESRD), Kidney Transplant
Recruiting
Guiding Optimal Blood Pressure Management in Peritoneal Dialysis Pilot Trial
End Stage Kidney Disease (ESKD), Hypertension (HTN)
RecruitingObservational study
Physical Impairments in Children With Chronic Renal Failure
Chronic Kidney Failure, Chronic Kidney Diseases
RecruitingPhase 1
A Study to Test the Safety of the Study Drug Fosmanogepix and How the Body Handles It in Adults With Severe Kidney Failure on Dialysis
End Stage Renal Disease on Dialysis, Adult
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paik Seong Lim, PhD principal investigator
Tungs' Taichung Metroharbour Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Probiotic packet in people with End Stage Renal Disease, run by Paik Seong Lim at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from Baseline Triglyceride/HDL cholesterol ratio at 3 months, 6 months and 3 months after the trial (time frame: baseline,3 months, 6 months and 3 months after the trial). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03066921, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2018.