Renal Insufficiency, ChronicNCT02179229
Effect of Pre- and Probiotics on P-cresol Plasma Levels in Patients Bearing a Kidney Allograft
A study testing SYNBIOTIC in people with Renal Insufficiency, Chronic, run by Federico II University at 1 site in Italy.
Trial summary
The purpose of this study is to establish whether a short treatment with the synbiotic combination Probinul neutro® may decrease the plasma concentration of the uremic toxin p-cresol in patients bearing a kidney allograft. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Renal Insufficiency, Chronic
- What is being tested?
- SYNBIOTIC
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteItaly
- Study dates
- Jun 2014to Aug 2015
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Previous renal allograft transplantation
Who cannot join
- severe infections
- diabetes
- malignancy
- history of food intolerance
- autoimmune disorders
- severe malnutrition or clinical conditions requiring artificial feeding
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Nutrition Unit of the Federico II University of Naples
Naples, 80131
Bruna Guida, MD, 0039-081-7462102, bguida@unina.it
Rossella Trio, BSci, rostrio@unina.it
About this study
The purpose of this study is to establish whether a short treatment with the synbiotic combination Probinul neutro® may decrease the plasma concentration of the uremic toxin p-cresol in patients bearing a kidney allograft. The effect of this treatment on plasma levels of immunosuppressant drugs will be evaluated as well.
Read the detailed description
Marked alterations in the gut microbiome take place in patients with chronic kidney disease (CKD) that show an overgrowth of aerobic bacteria such as Enterobacteriaceae, Halomonadaceae, Moraxellaceae, and Pseudomonadaceae and a decrease of anaerobic bacteria such as Lactobacillaceae and Prevotellaceae. These changes also occur after kidney transplantation. The dysbiotic microflora produces toxic compounds such as phenols, indoles, and amines that are absorbed through the intestinal mucosa and cause systemic toxicity. Compelling evidence showed the association of one of these compounds, p-cresol and of its main metabolite p-cresylsulfate, to cardiovascular risk and mortality in CKD. Therefore, new therapeutic strategies decreasing the generation or absorption of this uremic toxin are expected to have a favorable impact on the clinical course of the disease. In the present study, the effect of the synbiotic Probinul neutro® on p-cresol concentration in patients bearing a kidney allograft will be evaluated. Synbiotics are associations of prebiotics and probiotics. Probiotics are living microorganisms such as Bifidobacterium and Lactobacillus species that are administered to repopulate the gut with a "normal" microflora. Prebiotics are non-digestible food adjuncts that can be selectively fermented by probiotics or by normal intestinal microflora. In synbiotics the prebiotic and probiotic components synergize to restore the normal gut microflora. Indeed, the probiotic and prebiotic components of the synbiotic may both affect the gut microbiome through with different mechanisms. Probiotics contain bacteria that are part of the normal microbiome and are lowered in CKD such as anaerobes of Bifidobacterium sp. and facultative anaerobes of Lactobacillus sp. These bacterial species, unable to convert aromatic aminoacids into p-cresol, may replace by competition the p-cresol-producing bacteria of the dysbiotic microflora because of their ability to release substances toxic for the dysbiotic microflora such as the bacteriocins, and to activate innate and adaptive immunity. Prebiotics, instead, promote the growth of non-p-cresol producing commensal flora, including lactobacilli and bifidobacteria that selectively metabolize the oligosaccharides contained in prebiotic. The combined activity of pre- and probiotic is expected to reduce the production of p-cresol in the gut by decreasing the bacterial species generationg this compound. We recently showed that a short term treatment with Probinul neutro® causes, indeed, a decrease in p-cresol plasma levels in patients with satge III/IV CKD.
- Conditions
- Renal Insufficiency, Chronic
- Being tested
- CONTROL, SYNBIOTIC
- Keywords
- Kidney transplantation, pCresol, Immunosuppressant drugs
- Medical subject headings
- Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CONTROLDietary supplement
Also called PLACEBO
Placebo will be taken at home for four weeks as 5 g powder packets to be dissolved in water three times a day far from meals.
SYNBIOTICDietary supplement
Also called Probinul Neutro®
Probinul Neutro® will be taken at home for four weeks as 5 g powder packets to be dissolved in water three times a day far from meals.
| Study group | Role | What they receive |
|---|---|---|
| CONTROL | Placebo comparator | Patient in the CONTROL arm will receive a powder containing only tapioca-resistant starch comparable in colour, texture and taste to the synbiotic. Receives: Dietary Supplement: CONTROL |
| SYNBIOTIC | Experimental | Patients in this group will receive Probinul neutro® a synbiotic preparation containing (perpacket): lyophilised bacteria (5×109 Lactobacillus plantarum, 2×109 Lactobacillus casei subsp. rhamnosus and 2×109 Lactobacillus gasseri, 1×109 Bifidobacterium infantis and 1×109 Bifidobacterium longum, 1×109 Lactobacillus acidophilus, 1×109 Lactobacillus salivarius and 1×109 Lactobacillus sporogenes and 5×109 Streptococcus thermophilus), prebiotic inulin (2.2 g; VB Beneo Synergy 1) and 1.3 g of tapioca-resistant starch. Receives: Dietary Supplement: SYNBIOTIC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in p-cresol plasma concentration
Total p-cresol (free and glucurono- or sulpho-conjugates) plasma concentration will be assessed by reverse phase HPLC at baseline, 15 and 30 days after starting synbiotic treatment.
Measured: one month
Secondary outcomes (2)
Change in bowel habits
Defecation frequency or ease, stool shape, upper or lower abdominal pain, frequency of borborygms or flatus will be assessed by asking the patients to fill a a form for the scored evaluation of GI symptoms and stool characteristics
Measured: one month
Change in plasma immunosuppressant drug concentration
Plasma concentration of the different immunosuppressant assumed by the patient (mycophenolate mofetil, cyclosporin, tacrolimus, everolimus or sirolimus) will be assessed at baseline, 15 and 30 days after the beginning of the study.
Measured: one month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2014 (estimated)
- Study startJun 2014
- Primary completionJun 2015 (estimated)
- Study completionAug 2015 (estimated)
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 Renal Insufficiency, ChronicStudies of the same condition, open and under way.
- More trials run by Federico II UniversityThe sponsor's other registered studies.
- 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
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Federico II University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Bruna Guida, Federico II University
- Investigators
- Bruna Guida, MD, Principal investigator, Federico II University of Naples
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02179229
- Sponsor's protocol ID
- Syn-Graft Study
- Status last verified
- Jun 2014
- First submitted
- 27 Jun 2014
- Last updated
- 2 Jul 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Cooper TE, Scholes-Robertson N, Craig JC, Hawley CM, Howell M, Johnson DW, Teixeira-Pinto A, Jaure A, Wong G. Synbiotics, prebiotics and probiotics for solid organ transplant recipients. Cochrane Database Syst Rev. 2022 Sep 20;9(9):CD014804. doi: 10.1002/14651858.CD014804.pub2.
PubMed 36126902
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Pre- and Probiotics on P-cresol Plasma Levels in Patients Bearing a Kidney Allograft
- ClinicalTrials.gov ID
- NCT02179229
- Acronym / sponsor ID
- Syn-Graft Study
- Conditions
- Renal Insufficiency, Chronic
- Keywords
- Kidney transplantation, pCresol, Immunosuppressant drugs
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Federico II UniversityUniversity, hospital or other
- Study start
- Jun 2014
- Primary completion
- Jun 2015 (estimated)
- Study completion
- Aug 2015 (estimated)
- First posted
- 1 Jul 2014 (estimated)
- 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.
The purpose of this study is to establish whether a short treatment with the synbiotic combination Probinul neutro® may decrease the plasma concentration of the uremic toxin p-cresol in patients bearing a kidney allograft. The effect of this treatment on plasma levels of immunosuppressant drugs will be evaluated as well.
Detailed description
Marked alterations in the gut microbiome take place in patients with chronic kidney disease (CKD) that show an overgrowth of aerobic bacteria such as Enterobacteriaceae, Halomonadaceae, Moraxellaceae, and Pseudomonadaceae and a decrease of anaerobic bacteria such as Lactobacillaceae and Prevotellaceae. These changes also occur after kidney transplantation. The dysbiotic microflora produces toxic compounds such as phenols, indoles, and amines that are absorbed through the intestinal mucosa and cause systemic toxicity. Compelling evidence showed the association of one of these compounds, p-cresol and of its main metabolite p-cresylsulfate, to cardiovascular risk and mortality in CKD. Therefore, new therapeutic strategies decreasing the generation or absorption of this uremic toxin are expected to have a favorable impact on the clinical course of the disease. In the present study, the effect of the synbiotic Probinul neutro® on p-cresol concentration in patients bearing a kidney allograft will be evaluated. Synbiotics are associations of prebiotics and probiotics. Probiotics are living microorganisms such as Bifidobacterium and Lactobacillus species that are administered to repopulate the gut with a "normal" microflora. Prebiotics are non-digestible food adjuncts that can be selectively fermented by probiotics or by normal intestinal microflora. In synbiotics the prebiotic and probiotic components synergize to restore the normal gut microflora. Indeed, the probiotic and prebiotic components of the synbiotic may both affect the gut microbiome through with different mechanisms. Probiotics contain bacteria that are part of the normal microbiome and are lowered in CKD such as anaerobes of Bifidobacterium sp. and facultative anaerobes of Lactobacillus sp. These bacterial species, unable to convert aromatic aminoacids into p-cresol, may replace by competition the p-cresol-producing bacteria of the dysbiotic microflora because of their ability to release substances toxic for the dysbiotic microflora such as the bacteriocins, and to activate innate and adaptive immunity. Prebiotics, instead, promote the growth of non-p-cresol producing commensal flora, including lactobacilli and bifidobacteria that selectively metabolize the oligosaccharides contained in prebiotic. The combined activity of pre- and probiotic is expected to reduce the production of p-cresol in the gut by decreasing the bacterial species generationg this compound. We recently showed that a short term treatment with Probinul neutro® causes, indeed, a decrease in p-cresol plasma levels in patients with satge III/IV CKD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CONTROL | Placebo comparator | Dietary Supplement: CONTROLPatient in the CONTROL arm will receive a powder containing only tapioca-resistant starch comparable in colour, texture and taste to the synbiotic. |
| SYNBIOTIC | Experimental | Dietary Supplement: SYNBIOTICPatients in this group will receive Probinul neutro® a synbiotic preparation containing (perpacket): lyophilised bacteria (5×109 Lactobacillus plantarum, 2×109 Lactobacillus casei subsp. rhamnosus and 2×109 Lactobacillus gasseri, 1×109 Bifidobacterium infantis and 1×109 Bifidobacterium longum, 1×109 Lactobacillus acidophilus, 1×109 Lactobacillus salivarius and 1×109 Lactobacillus sporogenes and 5×109 Streptococcus thermophilus), prebiotic inulin (2.2 g; VB Beneo Synergy 1) and 1.3 g of tapioca-resistant starch. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Previous renal allograft transplantation
Key exclusion criteria (6 listed)
- severe infections
- diabetes
- malignancy
- history of food intolerance
- autoimmune disorders
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 |
|---|---|---|
| CONTROLAlso: PLACEBOPlacebo will be taken at home for four weeks as 5 g powder packets to be dissolved in water three times a day far from meals. | Dietary supplement | CONTROL |
| SYNBIOTICAlso: Probinul Neutro®Probinul Neutro® will be taken at home for four weeks as 5 g powder packets to be dissolved in water three times a day far from meals. | Dietary supplement | SYNBIOTIC |
Primary outcome
Change in p-cresol plasma concentration
Time frame: one month
Total p-cresol (free and glucurono- or sulpho-conjugates) plasma concentration will be assessed by reverse phase HPLC at baseline, 15 and 30 days after starting synbiotic treatment.
2 secondary outcomes
Change in bowel habits
Time frame: one month
Change in plasma immunosuppressant drug concentration
Time frame: one month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2014.
- Derived from this study: PubMed 36126902Cooper TE, Scholes-Robertson N, Craig JC, Hawley CM, Howell M, Johnson DW, Teixeira-Pinto A, Jaure A, Wong G. Synbiotics, prebiotics and probiotics for solid organ transplant recipients. Cochrane Database Syst Rev. 2022 Sep 20;9(9):CD014804. doi: 10.1002/14651858.CD014804.pub2.
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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.
Bruna Guida, MD principal investigator
Federico II University of Naples
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing SYNBIOTIC in people with Renal Insufficiency, Chronic, run by Federico II University at 1 site in Italy.
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 1 inclusion and 6 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: status not confirmed, as of the sponsor's last update on 2 Jul 2014. 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 Italy. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in p-cresol plasma concentration (time frame: one month). 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 NCT02179229, 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 2 Jul 2014.