Clinical trial NCT04979130: Comparing Semaglutide Versus Placebo on Intestinal Barrier Function in Type 2 Diabetes Mellitus (SIB)
Official title: A Randomized Parallel Comparison of Semaglutide Versus Placebo on Intestinal Barrier Function in Type 2 Diabetes Mellitus (SIB)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes
Chronic Inflammation
Intestinal Permeability
Keywords: T2D
Type 2 diabetes
Type 2 diabetes mellitus
obesity
intestinal permeability
chronic inflammation
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: Novo Nordisk A/S
First posted: 2021-07-28
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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


Eligibility criteria: 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).

Primary outcomes:
measure: Differences in lactulose mannitol ratio (LMR) test as a measure of intestinal permeability between treatment groups
timeFrame: Week 16 (visit 6)
Secondary outcomes:
measure: Differences between treatment groups in plasma LBP
timeFrame: Week 8 (visit 4), Week 16 (visit 6)
measure: Differences between treatment groups in Serum zonulin
timeFrame: Week 8 (visit 4), Week 16 (visit 6)
measure: Differences between treatment groups in Fecal Calprotectin
timeFrame: Week 8 (visit 4), Week 16 (visit 6)
measure: Differences between treatment groups in plasma IL-6
timeFrame: Week 8 (visit 4), Week 16 (visit 6)
measure: Differences between treatment groups in plasma IL-8
timeFrame: Week 8 (visit 4), Week 16 (visit 6)
measure: Differences between treatment groups in plasma TNFα
timeFrame: Week 8 (visit 4), Week 16 (visit 6)
measure: Differences between treatment groups in plasma hs-CRP
timeFrame: Week 8 (visit 4), Week 16 (visit 6)
Other outcomes:
measure: Exploratory: determine the effect of semaglutide as compared to placebo on intestinal microbiota in relation to changes in intestinal permeability and inflammatory markers
timeFrame: Visit 6 (week 16)
Locations:
city: Aurora
country: United States
facility: University of Colorado Anschutz
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Neda Rasouli, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Colorado, Denver
name: Joseph Onyiah, MD
role: PRINCIPAL_INVESTIGATOR
References: