Type 1 DiabetesProFOSNCT04635670
Effects of Probiotics and Fibers on Albuminuria in Persons With Type 1 Diabetes
A study testing Pro-/prebiotic Mix in people with Type 1 Diabetes and Nephropathy, run by Steno Diabetes Center Copenhagen at 1 site in Denmark.
Trial summary
The primary objective is to assess the impact of three months' treatment with pre-/probiotic mix on markers of nephropathy and other comorbidity related to diabetes. A double blinded, randomized, placebo-controlled crossover, single-centre study including 46 patients with type 1 diabetes and albuminuria. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Type 1 Diabetes, Nephropathy, Albuminuria
- What is being tested?
- Pro-/prebiotic Mix
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 41 participants
- Where
- 1 siteDenmark
- Study dates
- 29 Jun 2020to 8 Nov 2022
- 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 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Persons ≥ 18 years of age with a diagnosis of type 1 diabetes (age at onset <40 years; permanent insulin treatment initiated within 1 year of diagnosis)
- Albuminuria: UACR > 30 mg/g (in ≥2 out 3 morning spot urine collections prior to randomization)
- Participants must be on stable renin-angiotensin system blocking treatment 4 weeks before start of study drug and throughout study duration.
- Able to understand the written participant information and give informed consent
Who cannot join
- 1. Non-diabetic kidney disease indicated by medical history and/or laboratory findings 2. Known inflammatory bowel disease (IBD) 3. IBD symptoms due to investigator's opinion 4. Known celiac disease 5. Existing ostomy, malabsorption, history of bowel resection or bariatric surgery.
- 6. Heart valve replacement or history of endocarditis 7. Known rheumatic disorders treated with anti-inflammatory agents 8. Known hyperthyroidism or hypothyroidism 9. Active immunosuppressant therapy with systemic effect due to investigator's opinion 10. Current cancer treatment or within five years from baseline (except basal cell skin cancer or squamous cell skin cancer) 11. eGFR<15 ml/min/1.73m2, dialysis or kidney transplantation 12. Active antibiotic therapy until 30 days ahead of screening 13. Dietary supplements containing fibers (e.g. psyllium), probiotics or carotenoids until 30 days ahead of screening 14. The receipt of any investigational product 90 days prior to this trial 15. Unable to participate in study procedures 16. Any clinically significant disorder, except for conditions associated with type 1 diabetes, which in the Investigators opinion could interfere with the results of the trial 17. Pregnancy or lactation 18. Participation in another intervention study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Probiotics and Fibers on Markers of Nephropathy, Inflammation and Endothelial Dysfunction in Persons With Type 1 Diabetes and Albuminuria
The primary objective is to assess the impact of three months' treatment with pre-/probiotic mix on markers of nephropathy and other comorbidity related to diabetes. A double blinded, randomized, placebo-controlled crossover, single-centre study including 46 patients with type 1 diabetes and albuminuria. The treatment period is 2 x 12 weeks with 6 weeks washout. The primary outcome is to evaluate the effect of pre-/probiotic mix on albuminuria.
Read the detailed description
Recent data has pointed towards a link between gut microbiota and chronic kidney disease (CKD). It is hypothesized that defects in the intestinal barrier due to intestinal dysbiosis, a microbial imbalance in the intestines, allow bacterial toxins and other proinflammatory substances to pass and cause systemic inflammation that damages the endothelium. To reestablish the microbial symbiosis and thereby strengthening the gut barrier different treatments have been investigated. Fibers serve as substrate for the beneficial bacterial strains and probiotics are selected bacteria that exert a beneficial effect on the gut environment. It is hypothesized that a supplement of fructo-oligosaccharides and probiotics (Pre-/probiotic mix) will strengthen the gut barrier and thereby protect the endothelium and kidneys.
The aim of this study is to test whether af Pre-/probiotic mix, will have a beneficial impact on albuminuria in persons with type 1 diabetes and albuminuria.
46 patients with type 1 diabetes and albuminuria will be recruited from Steno Diabetes Center Copenhagen (SDCC) in accordance with the study in- and exclusion criteria.
- Conditions
- Type 1 Diabetes, Nephropathy, Albuminuria, Diabetic Kidney Disease
- Being tested
- Pro-/prebiotic Mix, Placebo
- Keywords
- probiotics, dietary fibers
- Medical subject headings
- Diabetes Mellitus, Type 1, Kidney Diseases, Albuminuria, Diabetic Nephropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pro-/prebiotic MixDietary supplement
Soluble powder for oral use of pre-/probiotic mix 3.0 g twice daily.
PlaceboDietary supplement
Soluble powder for oral use twice daily.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Soluble powder for oral use twice daily Receives: Dietary Supplement: Placebo |
| Active | Active comparator | The investigational product is soluble powder for oral use of pre-/probiotic mix 3.0 g twice daily. Receives: Dietary Supplement: Pro-/prebiotic Mix |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in albuminuria based on urinary albumin-creatinine ratio (UACR)
Three morning urine samples will be collected for assessment of UACR. The geometric mean of the 3 samples will be calculated.
Measured: 30 weeks. Samples will be collected before and after each og te two treatment periods.
Secondary outcomes (10)
Change in kidney function (GFR as plasma clearance of 99mTc-DTPA)
Renal function (GFR) and extracellular volume (ECV) will be assessed during 4 hours with the measurement plasma clearance of 99mTc-DTPA to provide accurate GFR measurement. A bolus of 0.5 mL Technetium-99m DTPA (approximately 10 MBq) is injected and blood samples are drawn at 0, 180, 200, 220 and 240 minutes after the injection. Urine is collected during the investigation. Plasma concentrations of 99mTc-DTPA at these time points are measured and used to calculate the plasma clearance of 99mTc-DTPA which approximates GFR.
Measured: 30 weeks. 99mTc-DTPA GFR will be performed after each of the two treatment periods.
Change in 24-hour blood pressure
24-hours blood pressure will be measured using a standard cuff-based device (boso TM-2430 PC2) that measures the blood pressure every 15 minutes between 07 in the morning and 23 in the evening and every 30 minutes during the night.
Measured: 30 weeks. 24h BP will be performed after each of the two treatment periods.
Change in microcirculation evaluated by the GlycoCheck device
GlycoCheck is a handheld video capillary microscope that measure glycocalyx thickness and sublingual capillary density under the tongue. The measurement will be performed by investigator and is a measure of the microcirculation damage. The distribution of the red blood cell column width at each capillary segment is used to calculate the perfused boundary region, which is the distance between the median and the outer edge of the red blood cell perfused lumen. The perfused boundary region reflects the thickness of the endothelial glycocalyx, based on the idea that loss of its integrity allows deeper penetration of the red blood cells into the gel-like layer covering the endothelial lining. Higher perfused boundary region, therefore, indicates thinner glycocalyx. The software also returns total and perfused capillary density in segments per millimeter square.
Measured: 30 weeks. GlycoCheck will be performed before and after each of the two treatment periods.
Change in endothelial dysfunction (von Willebrand factor, endothelin-1, ADMA, ICAM-1, VCAM-1 and E-selectin)
Biomarkers drawn from blood will include markers of endothelial dysfunction (von Willebrand factor, endothelin-1, ADMA, ICAM-1, VCAM-1 and E-selectin),
Measured: 30 weeks. Blood tests will be performed before and after each of the two treatment periods.
Change in urinary markers of oxidative stress F2-isoprostanes and 8-oxodG
Markers of oxidative stress (F2-isoprostanes and 8-oxodG) will be measured in urine by ELISA and multiplexing methods.
Measured: 30 weeks. Urine samples will be collected before and after each of the two treatment periods.
Change in intestinal inflammation measured by fecal calprotectin
Fecal samples will be collected for calprotectin analyses.
Measured: 30 weeks. Fecal samples will be collected before and after each of the two treatment periods.
Change in biomarkers of intestinal permeability (LPS and zonulin)
Biomarkers drawn from blood will include markers of intestinal permeability (LPS and zonulin)
Measured: 30 weeks. Blood tests will be performed before and after each of the two treatment periods.
Change in systemic inflammation (hs-TNT, TNF-alfa, IL6, IL8, IL1-beta, SAA, sICAM1, sICAM3 and suPAR)
Biomarkers drawn from blood will include markers of inflammation (hs-TNT, TNF-alfa, IL6, IL8, IL1-beta, SAA, sICAM1, sICAM3, suPAR)
Measured: 30 weeks. Blood tests will be performed before and after each of the two treatment periods.
Change in tubular function (NGAL, KIM-1, Beta2microglobulin, hepatocellular growth factor and adiponectin)
Markers of tubular kidney injury (NGAL, KIM-1, Beta2microglobulin, hepatocellular growth factor (HGF) and adiponectin) will be measured in urine by ELISA and multiplexing methods.
Measured: 30 weeks. Urine samples will be collected before and after each of the two treatment periods.
Change in autonomous neuropathy evaluated by VagusTM
Autonomic nervous system function will be evaluated with the VagusTM device. The heart rate will be measured by 5-minute resting measures and in response to deep breathing, position change from lying to standing position and by exhaling through a mouthpiece against 40 mmHg of pressure (Valsalva maneuver).
Measured: 30 weeks. Vagus test will be performed before and after each of the two treatment periods.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2020
- Study start29 Jun 2020
- Primary completion8 Nov 2022
- Study completion8 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 1 DiabetesStudies 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
- Crossover
- Model description
- Randomised, double blinded, placebo controlled, crossover, single-centre study. A total of 46 participants will be randomly assigned into two groups of 23 to a sequence of treatment (active followed by placebo or vice versa). Allocation will be masked for both participants and investigators.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Steno Diabetes Center Copenhagen
- Sponsor type
- University, hospital or other
- Collaborators
- dsm-firmenich Switzerland AG
- Responsible party
- Sponsor
- Investigators
- Peter Rossing, Proff, MD, Principal investigator, Steno Diabetes Center Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04635670
- Sponsor's protocol ID
- H19070341
- Acronym
- ProFOS
- Status last verified
- Feb 2022
- First submitted
- 20 Oct 2020
- Last updated
- 30 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Probiotics and Fibers on Markers of Nephropathy, Inflammation and Endothelial Dysfunction in Persons With Type 1 Diabetes and Albuminuria
- ClinicalTrials.gov ID
- NCT04635670
- Acronym / sponsor ID
- ProFOS / H19070341
- Conditions
- Type 1 Diabetes, Nephropathy, Albuminuria, Diabetic Kidney Disease
- Keywords
- probiotics, dietary fibers
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Steno Diabetes Center CopenhagenUniversity, hospital or other
- Collaborators
- dsm-firmenich Switzerland AG
- Study start
- 29 Jun 2020 (actual)
- Primary completion
- 8 Nov 2022 (actual)
- Study completion
- 8 Nov 2022 (actual)
- First posted
- 19 Nov 2020 (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.
The primary objective is to assess the impact of three months' treatment with pre-/probiotic mix on markers of nephropathy and other comorbidity related to diabetes. A double blinded, randomized, placebo-controlled crossover, single-centre study including 46 patients with type 1 diabetes and albuminuria. The treatment period is 2 x 12 weeks with 6 weeks washout. The primary outcome is to evaluate the effect of pre-/probiotic mix on albuminuria.
Detailed description
Recent data has pointed towards a link between gut microbiota and chronic kidney disease (CKD). It is hypothesized that defects in the intestinal barrier due to intestinal dysbiosis, a microbial imbalance in the intestines, allow bacterial toxins and other proinflammatory substances to pass and cause systemic inflammation that damages the endothelium. To reestablish the microbial symbiosis and thereby strengthening the gut barrier different treatments have been investigated. Fibers serve as substrate for the beneficial bacterial strains and probiotics are selected bacteria that exert a beneficial effect on the gut environment. It is hypothesized that a supplement of fructo-oligosaccharides and probiotics (Pre-/probiotic mix) will strengthen the gut barrier and thereby protect the endothelium and kidneys.
The aim of this study is to test whether af Pre-/probiotic mix, will have a beneficial impact on albuminuria in persons with type 1 diabetes and albuminuria.
46 patients with type 1 diabetes and albuminuria will be recruited from Steno Diabetes Center Copenhagen (SDCC) in accordance with the study in- and exclusion criteria.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomised, double blinded, placebo controlled, crossover, single-centre study. A total of 46 participants will be randomly assigned into two groups of 23 to a sequence of treatment (active followed by placebo or vice versa). Allocation will be masked for both participants and investigators.
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Dietary Supplement: PlaceboSoluble powder for oral use twice daily |
| Active | Active comparator | Dietary Supplement: Pro-/prebiotic MixThe investigational product is soluble powder for oral use of pre-/probiotic mix 3.0 g twice daily. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Persons ≥ 18 years of age with a diagnosis of type 1 diabetes (age at onset <40 years; permanent insulin treatment initiated within 1 year of diagnosis)
- Albuminuria: UACR > 30 mg/g (in ≥2 out 3 morning spot urine collections prior to randomization)
- Participants must be on stable renin-angiotensin system blocking treatment 4 weeks before start of study drug and throughout study duration.
- Able to understand the written participant information and give informed consent
Key exclusion criteria (2 listed)
- 1. Non-diabetic kidney disease indicated by medical history and/or laboratory findings 2. Known inflammatory bowel disease (IBD) 3. IBD symptoms due to investigator's opinion 4. Known celiac disease 5. Existing ostomy, malabsorption, history of bowel resection or bariatric surgery.
- 6. Heart valve replacement or history of endocarditis 7. Known rheumatic disorders treated with anti-inflammatory agents 8. Known hyperthyroidism or hypothyroidism 9. Active immunosuppressant therapy with systemic effect due to investigator's opinion 10. Current cancer treatment or within five years from baseline (except basal cell skin cancer or squamous cell skin cancer) 11. eGFR<15 ml/min/1.73m2, dialysis or kidney transplantation 12. Active antibiotic therapy until 30 days ahead of screening 13. Dietary supplements containing fibers (e.g. psyllium), probiotics or carotenoids until 30 days ahead of screening 14. The receipt of any investigational product 90 days prior to this trial 15. Unable to participate in study procedures 16. Any clinically significant disorder, except for conditions associated with type 1 diabetes, which in the Investigators opinion could interfere with the results of the trial 17. Pregnancy or lactation 18. Participation in another intervention study
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 |
|---|---|---|
| Pro-/prebiotic MixSoluble powder for oral use of pre-/probiotic mix 3.0 g twice daily. | Dietary supplement | Active |
| PlaceboSoluble powder for oral use twice daily. | Dietary supplement | Placebo |
Primary outcome
Change in albuminuria based on urinary albumin-creatinine ratio (UACR)
Time frame: 30 weeks. Samples will be collected before and after each og te two treatment periods.
Three morning urine samples will be collected for assessment of UACR. The geometric mean of the 3 samples will be calculated.
10 secondary outcomes
Change in kidney function (GFR as plasma clearance of 99mTc-DTPA)
Time frame: 30 weeks. 99mTc-DTPA GFR will be performed after each of the two treatment periods.
Change in 24-hour blood pressure
Time frame: 30 weeks. 24h BP will be performed after each of the two treatment periods.
Change in microcirculation evaluated by the GlycoCheck device
Time frame: 30 weeks. GlycoCheck will be performed before and after each of the two treatment periods.
Change in endothelial dysfunction (von Willebrand factor, endothelin-1, ADMA, ICAM-1, VCAM-1 and E-selectin)
Time frame: 30 weeks. Blood tests will be performed before and after each of the two treatment periods.
Change in urinary markers of oxidative stress F2-isoprostanes and 8-oxodG
Time frame: 30 weeks. Urine samples will be collected before and after each of the two treatment periods.
Change in intestinal inflammation measured by fecal calprotectin
Time frame: 30 weeks. Fecal samples will be collected before and after each of the two treatment periods.
Change in biomarkers of intestinal permeability (LPS and zonulin)
Time frame: 30 weeks. Blood tests will be performed before and after each of the two treatment periods.
Change in systemic inflammation (hs-TNT, TNF-alfa, IL6, IL8, IL1-beta, SAA, sICAM1, sICAM3 and suPAR)
Time frame: 30 weeks. Blood tests will be performed before and after each of the two treatment periods.
Change in tubular function (NGAL, KIM-1, Beta2microglobulin, hepatocellular growth factor and adiponectin)
Time frame: 30 weeks. Urine samples will be collected before and after each of the two treatment periods.
Change in autonomous neuropathy evaluated by VagusTM
Time frame: 30 weeks. Vagus test will be performed before and after each of the two treatment periods.
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 30 Oct 2023.
- Individual participant dataSharing planned: No
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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.
Peter Rossing, Proff, MD principal investigator
Steno Diabetes Center Copenhagen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Pro-/prebiotic Mix in people with Type 1 Diabetes and Nephropathy, run by Steno Diabetes Center Copenhagen at 1 site in Denmark.
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 4 inclusion and 2 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 30 Oct 2023. 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 Denmark. 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 in albuminuria based on urinary albumin-creatinine ratio (UACR) (time frame: 30 weeks. Samples will be collected before and after each og te two treatment periods.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Oct 2023.