Chronic Inflammation, Intestinal Permeability, Type 2 Diabetes
Conditions
Keywords
T2D, Type 2 diabetes, Type 2 diabetes mellitus, obesity, intestinal permeability, chronic inflammation
Brief summary
This study plans to learn more about the effect of semaglutide once weekly on intestinal permeability in individuals with type 2 diabetes.
Interventions
DRUGSemaglutide
Semaglutide 1.34 mg/mL solution for injection in 1.5 mL pre-filled PDS290 pen-injector provided by Novo Nordisk.
DRUGPlacebo
Semaglutide placebo, solution for injection, 1.5 mL pre-filled PDS290 pen-injector provided by Novo Nordisk.
Sponsors
Novo Nordisk A/S
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 89 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Differences in lactulose mannitol ratio (LMR) test as a measure of intestinal permeability between treatment groups | Week 16 (visit 6) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Differences between treatment groups in plasma LBP | Week 8 (visit 4), Week 16 (visit 6) | Marker of intestinal permeability |
| Differences between treatment groups in Serum zonulin | Week 8 (visit 4), Week 16 (visit 6) | Marker of intestinal permeability |
| Differences between treatment groups in Fecal Calprotectin | Week 8 (visit 4), Week 16 (visit 6) | Marker of intestinal inflammation |
| Differences between treatment groups in plasma IL-8 | Week 8 (visit 4), Week 16 (visit 6) | Marker of chronic inflammation |
| Differences between treatment groups in plasma TNFα | Week 8 (visit 4), Week 16 (visit 6) | Marker of chronic inflammation |
| Differences between treatment groups in plasma hs-CRP | Week 8 (visit 4), Week 16 (visit 6) | Marker of chronic inflammation |
| Differences between treatment groups in plasma IL-6 | Week 8 (visit 4), Week 16 (visit 6) | Marker of chronic inflammation |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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) | Microbiome study |
Countries
United States
Outcome results
None listed