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
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Diabetes Mellitus, Type 1
- Sponsor
- Steno Diabetes Center Copenhagen
- Enrollment
- 48
- Locations
- 2
- Primary Endpoint
- Intestinal inflammation
- Last Updated
- 6 years ago
Overview
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.
Investigators
Peter Rossing
Professor, MD, DMsc
Steno Diabetes Center Copenhagen
Eligibility Criteria
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
- •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
Outcomes
Primary Outcomes
Intestinal inflammation
Time Frame: Baseline to week 12
Change in concentration of fecal calprotectin determined by ELISA
Secondary Outcomes
- Kidney function(Baseline to week 12)
- Fecal intestinal alkaline phosphatase (IAP)(Baseline to week 12)
- Short-chain fatty acids (SCFAs)(Baseline to week 12)
- Albuminuria(Baseline to week 12)