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

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Butyful Study. Effect of Butyrate on Inflammation and Albuminuria in Patients With Albuminuria, Type 1 Diabetes and Intestinal Inflammation A Randomized, Double-blind, Placebo-controlled Study

Conditions
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Diabetes Mellitus, Type 1, Albuminuria

Intervention / Treatment
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* Dietary Supplement: Sodium butyrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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) Albuminuria: UACR > 30 mg/g documented in medical history Calprotectin quick-test result ≥ 50 μg/g (CalDetect 50/200, Preventis) between visit 1 and visit 2. Able to understand the written patient information and give informed consent Exclusion Criteria: Known inflammatory bowel disease IBD symptoms due to investigators opinion Known celiac disease Existing ostomy Known rheumatic disorders treated with anti-inflammatory agents Known hyperthyroidism or hypothyroidism Butyful Protocol - page 12 - Version 3, 25.02.2019 Active immunosuppressant therapy with systemic effect due to investigator's opinion Current cancer treatment or within five years from baseline (except basal cell skin cancer or squamous cell skin cancer) eGFR<15, dialysis or kidney transplantation Diagnosis of non-diabetic CKD Active antibiotic therapy until 30 days ahead of screening Unable to participate in study procedures Not able to assess calprotectin by quick test in two attempts 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 Pregnancy or lactation Participation in another intervention study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sodium butyrate<br>3.6 g sodium butyrate. 6 capsules twice daily for 12 weeks. | Dietary Supplement: Sodium butyrate<br>* 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.<br>|
| Placebo Comparator: Placebo<br>Placebo. 6 capsules twice daily for 12 weeks. | Dietary Supplement: Sodium butyrate<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intestinal inflammation | Change in concentration of fecal calprotectin determined by ELISA | Baseline to week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fecal intestinal alkaline phosphatase (IAP) | Change in IAP activity in feces assessed by colorimetric assay | Baseline to week 12 | 
| Short-chain fatty acids (SCFAs) | Change in acetate, propionate, butyrate and valerate concentration in feces measured by gas chromatography-mass spectrometry | Baseline to week 12 | 
| Albuminuria | Change in urinary albumin-creatinine ratio (UACR) | Baseline to week 12 | 
| Kidney function | Change in eGFR | Baseline to week 12 |