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

NCT ID: NCT04073927

Last Updated: 2019-09-03

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-05
• Study Completion Date: 2020-08-05

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.

Conditions

Diabetes Mellitus, Type 1; Albuminuria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Sodium butyrate

3.6 g sodium butyrate. 6 capsules twice daily for 12 weeks.

Group Type: ACTIVE_COMPARATOR

Sodium butyrate

Intervention Type: DIETARY_SUPPLEMENT

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

Placebo. 6 capsules twice daily for 12 weeks.

Group Type: PLACEBO_COMPARATOR

Sodium butyrate

Intervention Type: DIETARY_SUPPLEMENT

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.

Interventions

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.

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Folkhälsan Researech Center

OTHER

Sponsor Role: collaborator

Steno Diabetes Center Copenhagen

OTHER

Sponsor Role: lead

Responsible Party

Peter Rossing

Professor, MD, DMsc

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Peter Rossing, Professor

Role: PRINCIPAL_INVESTIGATOR

Steno Diabetes Center Copenhagen

Locations

Steno Diabetes Center Copenhagen

Gentofte Municipality, , Denmark

Site Status: RECRUITING

Folkhälsan Research Center, FinnDiane

Helsinki, , Finland

Site Status: NOT_YET_RECRUITING

Countries

Denmark; Finland

Central Contacts

Peter Rossing, Professor

Role: CONTACT

peter.rossing@regionh.dk

+45 30193383

Ninna Hahn Tougaard, MD

Role: CONTACT

ninna.hahn.tougaard.01@regionh.dk

+45 29399798

Facility Contacts

Peter Rossing, Professor

Role: primary

peter.rossing@regionh.dk

+45 30193383

Markku Lehto

Role: primary

markku.lehto@helsinki.fi

+358-40-7715484

Other Identifiers

H-18062027

Identifier Type: -

Identifier Source: org_study_id