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

NCT04979130 | Completed Phase 4 FDA Drug

• 1 other identifier: 21-2774
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Type 2 Diabetes; Chronic Inflammation; Intestinal Permeability

Keywords

T2D; Type 2 diabetes; Type 2 diabetes mellitus; obesity; intestinal permeability; chronic inflammation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Differences between treatment groups in plasma LBP

  Week 8 (visit 4), Week 16 (visit 6)

• Differences between treatment groups in Serum zonulin

  Week 8 (visit 4), Week 16 (visit 6)

• Differences between treatment groups in Fecal Calprotectin

  Week 8 (visit 4), Week 16 (visit 6)

• Differences between treatment groups in plasma IL-6

  Week 8 (visit 4), Week 16 (visit 6)

• Differences between treatment groups in plasma IL-8

  Week 8 (visit 4), Week 16 (visit 6)

Other Outcomes (1)

• Exploratory: determine the effect of semaglutide as compared to placebo on intestinal microbiota in relation to changes in intestinal permeability and inflammatory markers

  Visit 6 (week 16)

Study Arms (2)

SC semaglutide

EXPERIMENTAL

Participants receive a once weekly, subcutaneous, Semaglutide injection for 16 weeks in addition to the participants background metformin monotherapy. The participants in this arm will begin at a 0.25 mg dose during the randomization visit, at week 4 this will be escalated to a 0.5 mg dose and at week 8 it will be escalated again to a 1.0 mg dose if tolerable by the participant. If the participant cannot tolerate the 0.25 mg dose at randomization or the 0.5 mg dose at week 4 they will be withdrawn from the study.

Drug: Semaglutide

Placebo

PLACEBO COMPARATOR

Participants in this arm will be given a once weekly, subcutaneous, placebo injection matching the Semaglutide experimental arm in addition to their background metformin monotherapy.

Drug: Placebo

Interventions

Semaglutide DRUG

Semaglutide 1.34 mg/mL solution for injection in 1.5 mL pre-filled PDS290 pen-injector provided by Novo Nordisk.

Also known as: Ozempic, PDS290 pen-injector

SC semaglutide

Placebo DRUG

Semaglutide placebo, solution for injection, 1.5 mL pre-filled PDS290 pen-injector provided by Novo Nordisk.

Also known as: PDS290 pen-injector

Placebo

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Male or female, age above or equal to 18 years at the time of signing informed consent.
• Diagnosed with type 2 diabetes mellitus on metformin monotherapy
• Hemoglobin A1c \<8.0% (\<64 mmol/mol) on screening day
• Body mass index (BMI) ≥28 kg/m2
• 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).

You may not qualify if:

• Known or suspected hypersensitivity to trial product or related products.
• 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.
• Participation in any clinical trial of an approved or non-approved investigational medicinal product within 30 days before screening.
• Any disorder, which in the investigator's opinion might jeopardize patient's safety or compliance with the protocol.
• 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.
• Second anti-diabetic agent use within 3 months of screening.
• Chronic kidney disease defined as eGFR \< 30 mL/min/1.73 m2.
• C-reactive protein (hs-CRP \>10.0 mg/L) to eliminate patients with acute inflammatory process at the time of screening.
• Any recent infection or antibiotic use within 3 weeks
• Regular use (more than a week duration) of anti-inflammatory medication (steroid or NSAIDs) within 3 months of screening.
• Regular use (more than a week duration) of any digestive health supplements, such as probiotics or prebiotics within 3 months screening.
• Diagnosis of chronic intestinal inflammatory disease such as Crohn's disease, ulcerative colitis or irritable bowel syndrome.
• Prior bariatric or bowel surgery
• Heart failure presently classified as being in New York Heart Association (NYHA) Class IV.
• 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.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Novo Nordisk A/S: collaborator

Study Sites (1)

University of Colorado Anschutz

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Obesity

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Neda Rasouli, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

• Joseph Onyiah, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2021
• First Posted: July 28, 2021
• Study Start: January 1, 2022
• Primary Completion: October 16, 2024
• Study Completion: October 16, 2024
• Last Updated: March 20, 2025

Record last verified: 2025-03

Locations

US (1)