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

Diabetes Mellitus, Type 1 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04073927
• Other study ID #: H-18062027
• Status: Recruiting
• Phase: N/A
• Start date: August 5, 2019
• Est. completion date: August 5, 2020

Study information

• Verified date: August 2019
• Source: Steno Diabetes Center Copenhagen
• Contact: Peter Rossing, Professor
• Phone: +45 30193383
• Email: peter.rossing[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: August 5, 2020
• Est. primary completion date: August 5, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Albuminuria
• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Inflammation

Intervention

Dietary Supplement:
• Sodium 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.

Locations

Country	Name	City	State
Denmark	Steno Diabetes Center Copenhagen	Gentofte
Finland	Folkhälsan Research Center, FinnDiane	Helsinki

Sponsors (2)

Lead Sponsor	Collaborator
Steno Diabetes Center Copenhagen	Folkhälsan Researech Center

Countries where clinical trial is conducted

Denmark,  Finland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Intestinal inflammation	Change in concentration of fecal calprotectin determined by ELISA	Baseline to week 12
Secondary	Fecal intestinal alkaline phosphatase (IAP)	Change in IAP activity in feces assessed by colorimetric assay	Baseline to week 12
Secondary	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
Secondary	Albuminuria	Change in urinary albumin-creatinine ratio (UACR)	Baseline to week 12
Secondary	Kidney function	Change in eGFR	Baseline to week 12