Comparing Semaglutide Versus Placebo on Intestinal Barrier Function in Type 2 Diabetes Mellitus (SIB)
- Conditions
- Chronic InflammationType 2 DiabetesIntestinal Permeability
- Interventions
- Drug: Placebo
- Registration Number
- NCT04979130
- Lead Sponsor
- University of Colorado, Denver
- Brief Summary
This study plans to learn more about the effect of semaglutide once weekly on intestinal permeability in individuals with type 2 diabetes.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 69
- 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).
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Known or suspected hypersensitivity to trial product or related products.
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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.
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Participation in any clinical trial of an approved or non-approved investigational medicinal product within 30 days before screening.
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Any disorder, which in the investigator's opinion might jeopardize patient's safety or compliance with the protocol.
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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.
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Second anti-diabetic agent use within 3 months of screening.
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Chronic kidney disease defined as eGFR < 30 mL/min/1.73 m2.
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C-reactive protein (hs-CRP >10.0 mg/L) to eliminate patients with acute inflammatory process at the time of screening.
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Any recent infection or antibiotic use within 3 weeks
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Regular use (more than a week duration) of anti-inflammatory medication (steroid or NSAIDs) within 3 months of screening.
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Regular use (more than a week duration) of any digestive health supplements, such as probiotics or prebiotics within 3 months screening.
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Diagnosis of chronic intestinal inflammatory disease such as Crohn's disease, ulcerative colitis or irritable bowel syndrome.
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Prior bariatric or bowel surgery
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Heart failure presently classified as being in New York Heart Association (NYHA) Class IV.
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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.
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Personal or family history of multiple endocrine neoplasia type 2 (MEN2) or medullary thyroid carcinoma (MTC).
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History of chronic pancreatitis or history of acute pancreatitis within 6 months of screening.
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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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo 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. SC semaglutide Semaglutide 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.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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 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-6 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
Trial Locations
- Locations (1)
University of Colorado Anschutz
🇺🇸Aurora, Colorado, United States