- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04635670
Effects of Probiotics and Fibers on Albuminuria in Persons With Type 1 Diabetes (ProFOS)
Effects of Probiotics and Fibers on Markers of Nephropathy, Inflammation and Endothelial Dysfunction in Persons With Type 1 Diabetes and Albuminuria
Study Overview
Status
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Elisabeth Buur Stougaard, MD
- Phone Number: +45 21125957
- Email: elisabeth.buur.stougaard@regionh.dk
Study Locations
-
-
-
Gentofte, Denmark, 2820
- Steno Diabetes Center Copenhagen
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
Soluble powder for oral use twice daily
|
Soluble powder for oral use twice daily.
|
Active Comparator: Active
The investigational product is soluble powder for oral use of pre-/probiotic mix 3.0 g twice daily.
|
Soluble powder for oral use of pre-/probiotic mix 3.0 g twice daily.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
30 weeks. Samples will be collected before and after each og te two treatment periods.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
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.
|
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.
|
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.
|
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.
|
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.
|
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.
|
Biomarkers drawn from blood will include markers of endothelial dysfunction (von Willebrand factor, endothelin-1, ADMA, ICAM-1, VCAM-1 and E-selectin),
|
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.
|
Markers of oxidative stress (F2-isoprostanes and 8-oxodG) will be measured in urine by ELISA and multiplexing methods.
|
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.
|
Fecal samples will be collected for calprotectin analyses.
|
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.
|
Biomarkers drawn from blood will include markers of intestinal permeability (LPS and zonulin)
|
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.
|
Biomarkers drawn from blood will include markers of inflammation (hs-TNT, TNF-alfa, IL6, IL8, IL1-beta, SAA, sICAM1, sICAM3, suPAR)
|
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.
|
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.
|
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.
|
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).
|
30 weeks. Vagus test will be performed before and after each of the two treatment periods.
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in concentration of microbial uremic toxins in the blood; hippuric acid, kynurenic acid, indoxyl sulfate and p-cresol sulfate
Time Frame: 30 weeks. Blood tests will be performed before and after each of the two treatment periods.
|
Biomarkers will include markers of bacterial uremic toxins (hippuric acid, kynurenic acid, indoxyl sulfate and p-cresol sulfate).
|
30 weeks. Blood tests will be performed before and after each of the two treatment periods.
|
Change in Gut microbiome characterization assessed by 16S RNA sequencing
Time Frame: 30 weeks. Fecal samples will be collected before and after each of the two treatment periods.
|
Fecal samples will be collected at visit 2, 3, 4 and 5 for calprotectin and gut microbiome analyses.
Feces is collected according to current standard operation procedures in order to characterize the gut microbiome.
The fecal samples should be stored at -20 °C in the participants' freezer and be delivered to SDCC in the provided cooling bag no more than 48 hours after collection.
At SDCC the samples will be stored at -80°C.
The gut microbiome characterization is based on 16S rRNA gene sequencing.
After standardized microbial DNA extraction, the microbial DNA will be subjected to sequencing, microbial gene analyses, taxonomy analyses including enterotypes known species and unknown meta-species and functional annotation.
|
30 weeks. Fecal samples will be collected before and after each of the two treatment periods.
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Peter Rossing, Proff, MD, Steno Diabetes Center Copenhagen
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Immune System Diseases
- Autoimmune Diseases
- Urologic Diseases
- Urological Manifestations
- Endocrine System Diseases
- Diabetes Complications
- Urination Disorders
- Proteinuria
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Male Urogenital Diseases
- Diabetes Mellitus
- Kidney Diseases
- Diabetes Mellitus, Type 1
- Diabetic Nephropathies
- Albuminuria
Other Study ID Numbers
- H19070341
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Type 1 Diabetes
-
Poznan University of Medical SciencesUnknownDiabetes Mellitus Type 1 | Remission of Type 1 Diabetes | Chronic Complications of DiabetesPoland
-
Eledon PharmaceuticalsWithdrawnBrittle Type 1 Diabetes MellitusUnited States
-
National Institute of Allergy and Infectious Diseases...PPD; Rho Federal Systems Division, Inc.; Immune Tolerance Network (ITN)CompletedType 1 Diabetes Mellitus | T1DM | T1D | New-onset Type 1 Diabetes MellitusUnited States, Australia
-
Hoffmann-La RocheCompletedType 2 Diabetes, Type 1 DiabetesAustria, United Kingdom
-
Shanghai Changzheng HospitalRecruitingBrittle Type 1 Diabetes MellitusChina
-
Capillary Biomedical, Inc.TerminatedType 1 Diabetes | Type 1 Diabetes Mellitus | Diabetes Mellitus, Type I | Diabetes Mellitus, Insulin-Dependent, 1 | IDDMAustria
-
Capillary Biomedical, Inc.CompletedDiabetes Mellitus, Type 1 | Type 1 Diabetes | Type 1 Diabetes Mellitus | Diabetes Mellitus, Insulin-Dependent, 1Australia
-
AstraZenecaCompletedType 2 Diabetes Mellitus | Type 1 Diabetes MellitusUnited States
-
NYU Langone HealthNational Heart, Lung, and Blood Institute (NHLBI)Recruiting
-
Rabin Medical CenterDreaMed DiabetesTerminated
Clinical Trials on Placebo
-
SamA Pharmaceutical Co., LtdUnknownAcute Bronchitis | Acute Upper Respiratory Tract InfectionKorea, Republic of
-
National Institute on Drug Abuse (NIDA)CompletedCannabis UseUnited States
-
AstraZenecaParexel; Spandauer Damm 130; 14050; Berlin, GermanyCompletedMale Subjects With Type II Diabetes (T2DM)Germany
-
Heptares Therapeutics LimitedCompletedPharmacokinetics | Safety IssuesUnited Kingdom
-
GlaxoSmithKlineCompletedPulmonary Disease, Chronic ObstructiveUnited Kingdom, Netherlands
-
ItalfarmacoCompletedBecker Muscular DystrophyNetherlands, Italy
-
Shijiazhuang Yiling Pharmaceutical Co. LtdXuanwu Hospital, BeijingCompleted
-
GlaxoSmithKlineCompletedInfections, BacterialUnited States
-
West Penn Allegheny Health SystemCompletedAsthma | Allergic RhinitisUnited States