Type 2 DiabetesPhase 4SIBNCT04979130
Comparing Semaglutide Versus Placebo on Intestinal Barrier Function in Type 2 Diabetes Mellitus (SIB)
A Phase 4 study testing Semaglutide in people with Type 2 Diabetes and Chronic Inflammation, run by University of Colorado, Denver at 1 site in United States.
Trial summary
This study plans to learn more about the effect of semaglutide once weekly on intestinal permeability in individuals with type 2 diabetes. Read more about this study
- Who is it for?
- Ages 18 to 89 years
- Conditions the study is for
- Type 2 Diabetes, Chronic Inflammation, Intestinal Permeability
- What is being tested?
- Semaglutide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 69 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2022to 16 Oct 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 89 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
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- 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.
- Personal or family history of multiple endocrine neoplasia type 2 (MEN2) or medullary thyroid carcinoma (MTC).
- History of chronic pancreatitis or history of acute pancreatitis within 6 months of screening.
- 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).
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Anschutz
Aurora, Colorado, 80045
About this study
Official title: A Randomized Parallel Comparison of Semaglutide Versus Placebo on Intestinal Barrier Function in Type 2 Diabetes Mellitus (SIB)
This study plans to learn more about the effect of semaglutide once weekly on intestinal permeability in individuals with type 2 diabetes.
- Being tested
- Semaglutide, Placebo
- Keywords
- T2D, Type 2 diabetes, Type 2 diabetes mellitus, obesity, intestinal permeability, chronic inflammation
- Medical subject headings
- Diabetes Mellitus, Type 2, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SemaglutideDrug
Also called Ozempic, PDS290 pen-injector
Semaglutide 1.34 mg/mL solution for injection in 1.5 mL pre-filled PDS290 pen-injector provided by Novo Nordisk.
PlaceboDrug
Also called PDS290 pen-injector
Semaglutide placebo, solution for injection, 1.5 mL pre-filled PDS290 pen-injector provided by Novo Nordisk.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 16 (visit 6)
Secondary outcomes (7)
Differences between treatment groups in plasma LBP
Marker of intestinal permeability
Measured: Week 8 (visit 4), Week 16 (visit 6)
Differences between treatment groups in Serum zonulin
Marker of intestinal permeability
Measured: Week 8 (visit 4), Week 16 (visit 6)
Differences between treatment groups in Fecal Calprotectin
Marker of intestinal inflammation
Measured: Week 8 (visit 4), Week 16 (visit 6)
Differences between treatment groups in plasma IL-6
Marker of chronic inflammation
Measured: Week 8 (visit 4), Week 16 (visit 6)
Differences between treatment groups in plasma IL-8
Marker of chronic inflammation
Measured: Week 8 (visit 4), Week 16 (visit 6)
Differences between treatment groups in plasma TNFα
Marker of chronic inflammation
Measured: Week 8 (visit 4), Week 16 (visit 6)
Differences between treatment groups in plasma hs-CRP
Marker of chronic inflammation
Measured: Week 8 (visit 4), Week 16 (visit 6)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2021
- Study start1 Jan 2022
- Primary completion16 Oct 2024
- Study completion16 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- Novo Nordisk A/S
- Responsible party
- Sponsor
- Investigators
- Neda Rasouli, MD, Principal investigator, University of Colorado, DenverJoseph Onyiah, MD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04979130
- Sponsor's protocol ID
- 21-2774
- Acronym
- SIB
- Status last verified
- Mar 2025
- First submitted
- 16 Jul 2021
- Last updated
- 20 Mar 2025
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Parallel Comparison of Semaglutide Versus Placebo on Intestinal Barrier Function in Type 2 Diabetes Mellitus (SIB)
- ClinicalTrials.gov ID
- NCT04979130
- Acronym / sponsor ID
- SIB / 21-2774
- Keywords
- T2D, Type 2 diabetes, Type 2 diabetes mellitus, obesity, intestinal permeability, chronic inflammation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 69 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- Novo Nordisk A/S
- Study start
- 1 Jan 2022 (actual)
- Primary completion
- 16 Oct 2024 (actual)
- Study completion
- 16 Oct 2024 (actual)
- First posted
- 28 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study plans to learn more about the effect of semaglutide once weekly on intestinal permeability in individuals with type 2 diabetes.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SC semaglutide | Experimental | Drug: SemaglutideParticipants 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. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants in this arm will be given a once weekly, subcutaneous, placebo injection matching the Semaglutide experimental arm in addition to their background metformin monotherapy. |
Who may qualify
- Ages
- 18 to 89 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (22 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SemaglutideAlso: Ozempic, PDS290 pen-injectorSemaglutide 1.34 mg/mL solution for injection in 1.5 mL pre-filled PDS290 pen-injector provided by Novo Nordisk. | Drug | SC semaglutide |
| PlaceboAlso: PDS290 pen-injectorSemaglutide placebo, solution for injection, 1.5 mL pre-filled PDS290 pen-injector provided by Novo Nordisk. | Drug | Placebo |
Primary outcome
Differences in lactulose mannitol ratio (LMR) test as a measure of intestinal permeability between treatment groups
Time frame: 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.
7 secondary outcomes
Differences between treatment groups in plasma LBP
Time frame: Week 8 (visit 4), Week 16 (visit 6)
Differences between treatment groups in Serum zonulin
Time frame: Week 8 (visit 4), Week 16 (visit 6)
Differences between treatment groups in Fecal Calprotectin
Time frame: Week 8 (visit 4), Week 16 (visit 6)
Differences between treatment groups in plasma IL-6
Time frame: Week 8 (visit 4), Week 16 (visit 6)
Differences between treatment groups in plasma IL-8
Time frame: Week 8 (visit 4), Week 16 (visit 6)
Differences between treatment groups in plasma TNFα
Time frame: Week 8 (visit 4), Week 16 (visit 6)
Differences between treatment groups in plasma hs-CRP
Time frame: Week 8 (visit 4), Week 16 (visit 6)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Neda Rasouli, MD principal investigator
University of Colorado, Denver
Joseph Onyiah, MD principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Semaglutide in people with Type 2 Diabetes and Chronic Inflammation, run by University of Colorado, Denver at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Differences in lactulose mannitol ratio (LMR) test as a measure of intestinal permeability between treatment groups (time frame: Week 16 (visit 6)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2025; AzTrials last refreshed its copy on 30 Oct 2026.