Albuminuria, Diabetes Mellitus, Type 1
Conditions
Brief summary
The objective is to assess the impact of 12 weeks supplement of sodium-butyrate twice daily or placebo on intestinal inflammation and albuminuria. A randomized, placebo-controlled, double-blind, two-site trial including 48 patients with type 1 diabetes, albuminuria and intestinal inflammation. Participants will be randomized 1:1 to active treatment or placebo for a period of 12 weeks. The primary endpoint is change from baseline to week 12 in intestinal inflammation, measured by fecal calprotectin.
Detailed description
In patients with type 1 diabetes, increased intestinal inflammation, reduced gut barrier function and resulting influx of proinflammatory molecules have been described. This might contribute to systemic inflammation and the development of diabetic complications like nephropathy and ischemic heart disease. Interestingly, the gut microbiota is altered in persons with type 1 diabetes, who have less butyrate-producing bacteria. The short-chain fatty acid butyrate improves the intestinal barrier function, and the altered bacterial composition is hypothesized to play a role in the intestinal inflammation. Treatment with butyrate has improved metabolic, colonic and renal function in animal models of chronic kidney disease. The aim of the study is to test whether orally ingested sodium butyrate can reduce intestinal inflammation in patients with type 1 diabetes and albuminuria in a randomized, placebo-controlled, double-blind, two-site trial. Persons with type 1 diabetes and albuminuria are recruited from Steno Diabetes Center Copenhagen (SDCC) and Folkhälsan Research Center, FinnDiane, Helsinki, Finland and screened for intestinal inflammation. 48 participants with intestinal inflammation (fecal calprotectin ≥50 μg/g) are randomized to receive 3.6 g sodium butyrate or placebo for 12 weeks.
Interventions
DIETARY_SUPPLEMENTSodium butyrate
Sodium butyrate Class: Fatty acids Ingredients (100 g): Na-butyrate (50 g), acylglycerol (mono- di, -triacylglycerol; 42 g), bee wax (5 g), sodium alginate E401 (2 g), emulsifier (0.5 g). The capsules contain granulated sodium butyrate and are coated with a sodium alginate membrane.
Sponsors
Folkhälsan Researech Center
Steno Diabetes Center Copenhagen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female patients ≥ 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) 2. Albuminuria: UACR \> 30 mg/g documented in medical history 3. Calprotectin quick-test result ≥ 50 μg/g (CalDetect 50/200, Preventis) between visit 1 and visit 2. 4. Able to understand the written patient information and give informed consent
Exclusion criteria
1. Known inflammatory bowel disease 2. IBD symptoms due to investigators opinion 3. Known celiac disease 4. Existing ostomy 5. Known rheumatic disorders treated with anti-inflammatory agents 6. Known hyperthyroidism or hypothyroidism Butyful Protocol - page 12 - Version 3, 25.02.2019 7. Active immunosuppressant therapy with systemic effect due to investigator's opinion 8. Current cancer treatment or within five years from baseline (except basal cell skin cancer or squamous cell skin cancer) 9. eGFR\<15, dialysis or kidney transplantation 10. Diagnosis of non-diabetic CKD 11. Active antibiotic therapy until 30 days ahead of screening 12. Unable to participate in study procedures 13. Not able to assess calprotectin by quick test in two attempts 14. Any clinically significant disorder, except for conditions associated with type 1 DM history, which in the Investigators opinion could interfere with the results of the trial 15. Pregnancy or lactation 16. Participation in another intervention study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intestinal inflammation | Baseline to week 12 | Change in concentration of fecal calprotectin determined by ELISA |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fecal intestinal alkaline phosphatase (IAP) | Baseline to week 12 | Change in IAP activity in feces assessed by colorimetric assay |
| Short-chain fatty acids (SCFAs) | Baseline to week 12 | Change in acetate, propionate, butyrate and valerate concentration in feces measured by gas chromatography-mass spectrometry |
| Albuminuria | Baseline to week 12 | Change in urinary albumin-creatinine ratio (UACR) |
| Kidney function | Baseline to week 12 | Change in eGFR |
Countries
Denmark, Finland
Contacts
Primary ContactPeter Rossing, Professor
Backup ContactNinna Hahn Tougaard, MD
Outcome results
None listed