Effects of Probiotics and Fibers on Albuminuria in Persons With Type 1 Diabetes

NCT04635670 | Completed DMC

• 1 other identifier: H19070341
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Type 1 Diabetes; Nephropathy; Albuminuria; Diabetic Kidney Disease

Keywords

probiotics, dietary fibers

Outcome Measures

Primary Outcomes (1)

• 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.

  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)

  30 weeks. 99mTc-DTPA GFR will be performed after each of the two treatment periods.

• Change in 24-hour blood pressure

  30 weeks. 24h BP will be performed after each of the two treatment periods.

• Change in microcirculation evaluated by the GlycoCheck device

  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)

  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

  30 weeks. Urine samples will be collected before and after each of the two treatment periods.

Other Outcomes (2)

• Change in concentration of microbial uremic toxins in the blood; 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

  30 weeks. Fecal samples will be collected before and after each of the two treatment periods.

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Soluble powder for oral use twice daily

Dietary Supplement: Placebo

Active

ACTIVE COMPARATOR

The investigational product is soluble powder for oral use of pre-/probiotic mix 3.0 g twice daily.

Dietary Supplement: Pro-/prebiotic Mix

Interventions

Pro-/prebiotic Mix DIETARY_SUPPLEMENT

Soluble powder for oral use of pre-/probiotic mix 3.0 g twice daily.

Active

Placebo DIETARY_SUPPLEMENT

Soluble powder for oral use twice daily.

Placebo

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• \. 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.
• \. 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

Sponsors & Collaborators

• Steno Diabetes Center Copenhagen: lead
• DSM Nutritional Products, Inc.: collaborator

Study Sites (1)

Steno Diabetes Center Copenhagen

Gentofte Municipality, 2820, Denmark

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Kidney Diseases; Albuminuria; Diabetic Nephropathies

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Proteinuria; Urination Disorders; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Complications

Study Officials

• Peter Rossing, Proff, MD

  Steno Diabetes Center Copenhagen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Allocation will be masked for both participants and investigators. Only after completion of all study visits by all participants and after database lock the randomization code will be opened.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 20, 2020
• First Posted: November 19, 2020
• Study Start: June 29, 2020
• Primary Completion: November 8, 2022
• Study Completion: November 8, 2022
• Last Updated: October 30, 2023

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)