Effect of Butyrate on Inflammation and Albuminuria in Patients With Albuminuria, Type 1 Diabetes and Intestinal Inflammation
Effect of Butyrate on Inflammation and Albuminuria in Patients With Albuminuria, Type 1 Diabetes and Intestinal Inflammation
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.
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.
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