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

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

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.

Study Overview

• Status: Unknown
• Conditions: Diabetes Mellitus, Type 1; Albuminuria
• Intervention / Treatment: Dietary supplement: Sodium butyrate

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.

• Study Type: Interventional
• Enrollment (Anticipated): 48
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Peter Rossing, Professor; Phone Number: +45 30193383; Email: peter.rossing@regionh.dk

Study Locations

• Denmark
  • Gentofte, Denmark, 2820
    • Recruiting
    • Steno Diabetes Center Copenhagen
    • Contact: Peter Rossing, Professor; Phone Number: +45 30193383; Email: peter.rossing@regionh.dk
• Finland
  • Helsinki, Finland, FIN-00290
    • Not yet recruiting
    • Folkhälsan Research Center, FinnDiane
    • Contact: Markku Lehto; Phone Number: +358-40-7715484; Email: markku.lehto@helsinki.fi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sodium butyrate; 3.6 g sodium butyrate. 6 capsules twice daily for 12 weeks.	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.
Placebo Comparator: Placebo; Placebo. 6 capsules twice daily for 12 weeks.	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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Steno Diabetes Center Copenhagen
• Collaborators: Folkhälsan Researech Center
• Investigators: Principal Investigator: Peter Rossing, Professor, Steno Diabetes Center Copenhagen

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2019
• Primary Completion (Anticipated): August 5, 2020
• Study Completion (Anticipated): August 5, 2020

Study Registration Dates

• First Submitted: August 16, 2019
• First Submitted That Met QC Criteria: August 28, 2019
• First Posted (Actual): August 29, 2019

Study Record Updates

• Last Update Posted (Actual): September 3, 2019
• Last Update Submitted That Met QC Criteria: August 29, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Urological Manifestations; Endocrine System Diseases; Urination Disorders; Proteinuria; Diabetes Mellitus; Diabetes Mellitus, Type 1; Inflammation; Albuminuria; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Histamine Antagonists; Histamine Agents; Butyric Acid
• Other Study ID Numbers: H-18062027

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No