Comparing Semaglutide Versus Placebo on Intestinal Barrier Function in Type 2 Diabetes Mellitus (SIB)

Type 2 Diabetes Clinical Trial

— SIB  

Official title:

A Randomized Parallel Comparison of Semaglutide Versus Placebo on Intestinal Barrier Function in Type 2 Diabetes Mellitus (SIB)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04979130
• Other study ID #: 21-2774
• Status: Recruiting
• Phase: Phase 4
• Start date: January 1, 2022
• Est. completion date: December 31, 2023

Study information

• Verified date: June 2023
• Source: University of Colorado, Denver
• Contact: Neda Rasouli, MD
• Phone: 303-724-4651
• Email: neda.rasouli[@]cuanschutz.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study plans to learn more about the effect of semaglutide once weekly on intestinal permeability in individuals with type 2 diabetes.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 89 Years

Eligibility

Inclusion Criteria:

1. Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial, except for protocol described pre-screening activities, which require a separate informed consent.

2. Male or female, age above or equal to 18 years at the time of signing informed consent.

3. Diagnosed with type 2 diabetes mellitus on metformin monotherapy

4. Hemoglobin A1c <8.0% (<64 mmol/mol) on screening day

5. Body mass index (BMI) =28 kg/m2

6. Low-grade inflammation, defined as elevated high sensitivity C-reactive protein (hs- CRP >1.0 and =10 mg/L). Impaired intestinal barrier function results in activation of inflammatory pathway; therefore, excluding subjects with no evidence of inflammation (hs-CRP = 1 mg/L) will help to enrich our study population. Similar threshold for hs-CRP as a marker of "residual inflammatory risk" (29) has been previously used as an independent predictor of future vascular events (26, 30).

Exclusion Criteria:

1. Known or suspected hypersensitivity to trial product or related products.

2. Female who is pregnant, breast-feeding or intends to become pregnant or is of child- bearing potential and not using a highly effective contraceptive method.

3. Participation in any clinical trial of an approved or non-approved investigational medicinal product within 30 days before screening.

4. Any disorder, which in the investigator's opinion might jeopardize patient's safety or compliance with the protocol.

5. Any of the following: myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischemic attack (TIA) within the past 60 days prior to the day of screening.

6. Second anti-diabetic agent use within 3 months of screening.

7. Chronic kidney disease defined as eGFR < 30 mL/min/1.73 m2.

8. C-reactive protein (hs-CRP >10.0 mg/L) to eliminate patients with acute inflammatory process at the time of screening.

9. Any recent infection or antibiotic use within 3 weeks

10. Regular use (more than a week duration) of anti-inflammatory medication (steroid or NSAIDs) within 3 months of screening.

11. Regular use (more than a week duration) of any digestive health supplements, such as probiotics or prebiotics within 3 months screening.

12. Diagnosis of chronic intestinal inflammatory disease such as Crohn's disease, ulcerative colitis or irritable bowel syndrome.

13. Prior bariatric or bowel surgery

14. Heart failure presently classified as being in New York Heart Association (NYHA) Class IV.

15. Presence or history of malignant neoplasm within 5 years prior to the day of screening. Basal and squamous cell skin cancer and any carcinoma in-situ is allowed.

16. Personal or family history of multiple endocrine neoplasia type 2 (MEN2) or medullary thyroid carcinoma (MTC).

17. History of chronic pancreatitis or history of acute pancreatitis within 6 months of screening.

18. Chronic consumption of > 2 alcoholic standard drinks per day as defined by:

• 12 ounces of beer (5% alcohol content).
• 8 ounces of malt liquor (7% alcohol content).
• 5 ounces of wine (12% alcohol content).
• 1.5 ounces or a "shot" of 80-proof (40% alcohol content) distilled spirits or liquor (e.g., gin, rum, vodka, whiskey).

Related Conditions & MeSH terms

• Chronic Inflammation
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Inflammation
• Intestinal Permeability
• Type 2 Diabetes

Intervention

Drug:
• Semaglutide
Semaglutide 1.34 mg/mL solution for injection in 1.5 mL pre-filled PDS290 pen-injector provided by Novo Nordisk.
• Placebo
Semaglutide placebo, solution for injection, 1.5 mL pre-filled PDS290 pen-injector provided by Novo Nordisk.

Locations

Country	Name	City	State
United States	University of Colorado Anschutz	Aurora	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
University of Colorado, Denver	Novo Nordisk A/S

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory: determine the effect of semaglutide as compared to placebo on intestinal microbiota in relation to changes in intestinal permeability and inflammatory markers	Microbiome study	Visit 6 (week 16)
Primary	Differences in lactulose mannitol ratio (LMR) test as a measure of intestinal permeability between treatment groups	The ratio of lactulose to mannitol will be measured in urine collected within 6 hours after ingestion of dual sugar. This ratio predominantly reflects small intestine permeability.	Week 16 (visit 6)
Secondary	Differences between treatment groups in plasma LBP	Marker of intestinal permeability	Week 8 (visit 4), Week 16 (visit 6)
Secondary	Differences between treatment groups in Serum zonulin	Marker of intestinal permeability	Week 8 (visit 4), Week 16 (visit 6)
Secondary	Differences between treatment groups in Fecal Calprotectin	Marker of intestinal inflammation	Week 8 (visit 4), Week 16 (visit 6)
Secondary	Differences between treatment groups in plasma IL-6	Marker of chronic inflammation	Week 8 (visit 4), Week 16 (visit 6)
Secondary	Differences between treatment groups in plasma IL-8	Marker of chronic inflammation	Week 8 (visit 4), Week 16 (visit 6)
Secondary	Differences between treatment groups in plasma TNFa	Marker of chronic inflammation	Week 8 (visit 4), Week 16 (visit 6)
Secondary	Differences between treatment groups in plasma hs-CRP	Marker of chronic inflammation	Week 8 (visit 4), Week 16 (visit 6)