Diabetes Mellitus, Type 2Phase 1NCT02650206
Effect of Liraglutide (Victoza) on Inflammation in Human Adipose Tissue and Blood
A Phase 1 study testing Victoza (liraglutide) with dietician monitoring in people with Diabetes Mellitus, Type 2 and Diabetes Mellitus, Type II, run by Stanford University at 1 site in United States.
Trial summary
The objective of this study is to test the hypothesis that liraglutide (commonly known as Victoza) can promote an anti-inflammatory macrophage phenotype in human adipose tissue and blood, thereby reducing localized and systemic inflammation which are risk factors for cardiovascular disease and may contribute to… Read more about this study
- Who is it for?
- Ages 40 to 69 years
- Conditions the study is for
- Diabetes Mellitus, Type 2, Diabetes Mellitus, Type II, Diabetes Mellitus, Adult-Onset
- What is being tested?
- Victoza (liraglutide) with dietician monitoring
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 56 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2015to 27 Sep 2019
- Phase
- Phase 1
- 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 40 to 69 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- BMI between 25 and 42 kg/m2
- Diet-controlled diabetics, or diabetics on Metformin that have permission from Primacy Care Physician to wash-out of the drug for 6 weeks prior to the study and for the duration of the study
- HbA1C between 6.0 - 7.9 (those on Metformin must have a HbA1c level below 7.5 prior to wash-out period)
- Fasting Blood Glucose < 150 mg/dl
- Women must be post-menopausal or surgically sterile within age range
- Subjects must live in vicinity of Stanford University
Who cannot join
- Prior Bariatric surgery
- Personal or family history of medullary thyroid cancer
- MEN2 Syndrome
- Thyroid Nodules (not evaluated by PCP)
- Pancreatitis (acute or chronic)
- Gallstones
Show all 15Show fewer
- Fasting plasma triglycerides > 400 mg/dl
- Cardiovascular disease
- Major organ disease
- Unstable hypertension (BP >160/100 mm Hg)
- Heavy alcohol use
- Self-reported weight change of >2kg over past 6 weeks
- Medication known to affect blood glucose, insulin sensitivity, or inflammation
- NSAIDs (must cease use 4 weeks prior to study enrollment)
- Previous use of liraglutide, Januvia, Byetta, or Lira.
Trial locations and contacts
1 site in 1 country.
United States1 site
Freidenrich Center for Translational Research (FCTR)
Stanford, California, 94305
About this study
Official title: Effect of Liraglutide on Macrophage Polarization in Human Adipose Tissue and Peripheral Blood
The objective of this study is to test the hypothesis that liraglutide (commonly known as Victoza) can promote an anti-inflammatory macrophage phenotype in human adipose tissue and blood, thereby reducing localized and systemic inflammation which are risk factors for cardiovascular disease and may contribute to hyperglycemia. This will be done after 4 weeks of treatment during which weight will remain stable, and again after 12 weeks, during which liraglutide-related weight loss occurs.
Read the detailed description
It has now been established that the high risk of cardiovascular disease that is associated with obesity and type 2 diabetes is related to the systemic inflammation that underlies these conditions. Previous studies have shown that there are numerous types of immune cells in human adipose tissue, some of these are the macrophages. These cells can exist in two states: M2, which can inhibit classical inflammatory response, and M1 which secrete proinflammatory cytokines. The investigators have data to suggest that the role of inflammatory cells in adipose tissue is a strong contributor to systemic inflammation. A recent study showed that a GLP-1 analog (liraglutide, also known as Victoza) may help decrease inflammation via promoting M2 differentiation of macrophages. The purpose of this study is to quantify macrophage phenotype (M1 vs M2) in subcutaneous adipose tissue in moderately-obese diet controlled diabetics at baseline, after four weeks of weight-maintenance using liraglutide, and after 12 weeks of liraglutide treatment as compared to placebo.
Aim 1: Quantify M1 and M2 (surface and intracellular markers) polarization via flow cytometry in subcutaneous abdominal adipose tissue and peripheral blood mononuclear cells at baseline and after 4 weeks administration of liraglutide versus placebo to weight-stable, obese, type 2 diabetic patients. Weight loss will be prevented in order to ascertain the effect of liraglutide alone.
Aim 2: Quantify M1 and M2 (surface and intracellular markers) polarization via flow cytometry in subcutaneous adipose tissue and peripheral blood mononuclear cells after 12 weeks of liraglutide treatment, during which dietary restrictions are lifted and spontaneous weight loss, as would occur in the clinical setting, is allowed. To eliminate confounding by weight loss, a placebo-treated group will undergo matched dietary weight loss for comparison to the liraglutide group to ascertain whether changes in macrophage polarization at 12 weeks are greater in the liraglutide group.
Aim 3: Quantify macrophage-mediated localized and systemic inflammation by measuring M1/M2-related inflammatory cytokines in adipose tissue and peripheral blood after 4 and 12 weeks administration of liraglutide versus placebo to obese, type 2 diabetic patients.
- Conditions
- Diabetes Mellitus, Type 2, Diabetes Mellitus, Type II, Diabetes Mellitus, Adult-Onset, Inflammation
- Being tested
- Victoza (liraglutide) with dietician monitoring, Placebo with dietician monitoring
- Keywords
- diabetes, macrophage, inflammation, adipose tissue, weight loss, liraglutide
- Medical subject headings
- Diabetes Mellitus, Type 2, Inflammation, Diabetes Mellitus, Weight Loss
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Victoza (liraglutide) with dietician monitoringDrug
Also called liraglutide
Victoza (liraglutide), an FDA-approved medication, is a glucagon-like peptide-1 (GLP-1) receptor agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Subjects with this intervention will be followed by the MD and dietician throughout the study to monitor progress through 4 week period of weight maintenance and 8 week period of weight loss.
Placebo with dietician monitoringOther
Subjects will not receive the study drug, but will be followed by the MD and dietician throughout the study to monitor progress through 4 week period of weight maintenance and 8 week period of weight loss.
| Study group | Role | What they receive |
|---|---|---|
| Liraglutide group | Experimental | Drug with diet control intervention: Subjects assigned to this group receive blinded pens containing liraglutide (commonly known as Victoza), manufactured by Novo Nordisk. Subjects will inject 0.6 mg daily into abdomen during the first week of the study, and if tolerated, will increase dose to 1.2 mg the second week of the study, and then up to 1.8 mg daily from the third week until the end of the 12-week study. Any adverse symptoms as well as fasting blood glucose will be monitored weekly for safety.
Subjects, with the guidance of the study's dietitian, will remain weight-stable for the first four weeks of the study, and then will be allowed to lose weight for the remaining eight weeks of the study. Receives: Drug: Victoza (liraglutide) with dietician monitoring |
| Placebo group | Placebo comparator | Diet control-only intervention: Subjects assigned to this group receive blinded pens containing placebo (normal saline) instead of liraglutide (commonly known as Victoza). Subjects will inject 0.6 mg of placebo daily during the first week of the study, will increase to 1.2 mg the second week of the study, and then up to 1.8 mg daily from the third week until the end of the 12-week study. Any adverse symptoms as well as fasting blood glucose will be monitored weekly for safety.
Subjects, with the guidance of the study's dietitian, will remain weight-stable for the first four weeks of the study, and then will be allowed to lose weight for the remaining eight weeks of the study. Receives: Other: Placebo with dietician monitoring |
What is being measured
The primary outcome is the main question the study is designed to answer.
Macrophage polarization: % M2 macrophages in adipose tissue and peripheral blood according to positivity for cell surface markers (measured by flow cytometry).
Measured: 30 months
Secondary outcomes (3)
Inflammation, localized: Pro- and anti-inflammatory cytokines will be measured (IL6, IL-8, TNF-α, MCP-1, cell surface markers, and adiponectin) by rtPCR in adipose tissue and blood macrophages
Measured: 30 months
Inflammation, systemic: Plasma pro/anti-inflammatory cytokines: IL-6, hsCRP, cell surface markers, and adiponectin will be measured in plasma.
Measured: 30 months
Macrophage polarization: M1 to M2 ratio in adipose tissue and peripheral blood according to cell surface markers (measured by flow cytometry)
Measured: 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2016 (estimated)
- Study startJan 2015
- Primary completion27 Sep 2019
- Study completion27 Sep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- More trials run by Stanford UniversityThe 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 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tracey McLaughlin, Stanford University
- Investigators
- Tracey McLaughlin, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02650206
- Sponsor's protocol ID
- 31063
- Status last verified
- Jun 2020
- First submitted
- 5 Jun 2015
- Last updated
- 9 Jun 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Liraglutide on Macrophage Polarization in Human Adipose Tissue and Peripheral Blood
- ClinicalTrials.gov ID
- NCT02650206
- Acronym / sponsor ID
- 31063
- Conditions
- Diabetes Mellitus, Type 2, Diabetes Mellitus, Type II, Diabetes Mellitus, Adult-Onset, Inflammation
- Keywords
- diabetes, macrophage, inflammation, adipose tissue, weight loss, liraglutide
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- Jan 2015 (actual)
- Primary completion
- 27 Sep 2019 (actual)
- Study completion
- 27 Sep 2019 (actual)
- First posted
- 8 Jan 2016 (estimated)
- 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.
The objective of this study is to test the hypothesis that liraglutide (commonly known as Victoza) can promote an anti-inflammatory macrophage phenotype in human adipose tissue and blood, thereby reducing localized and systemic inflammation which are risk factors for cardiovascular disease and may contribute to hyperglycemia. This will be done after 4 weeks of treatment during which weight will remain stable, and again after 12 weeks, during which liraglutide-related weight loss occurs.
Detailed description
It has now been established that the high risk of cardiovascular disease that is associated with obesity and type 2 diabetes is related to the systemic inflammation that underlies these conditions. Previous studies have shown that there are numerous types of immune cells in human adipose tissue, some of these are the macrophages. These cells can exist in two states: M2, which can inhibit classical inflammatory response, and M1 which secrete proinflammatory cytokines. The investigators have data to suggest that the role of inflammatory cells in adipose tissue is a strong contributor to systemic inflammation. A recent study showed that a GLP-1 analog (liraglutide, also known as Victoza) may help decrease inflammation via promoting M2 differentiation of macrophages. The purpose of this study is to quantify macrophage phenotype (M1 vs M2) in subcutaneous adipose tissue in moderately-obese diet controlled diabetics at baseline, after four weeks of weight-maintenance using liraglutide, and after 12 weeks of liraglutide treatment as compared to placebo.
Aim 1: Quantify M1 and M2 (surface and intracellular markers) polarization via flow cytometry in subcutaneous abdominal adipose tissue and peripheral blood mononuclear cells at baseline and after 4 weeks administration of liraglutide versus placebo to weight-stable, obese, type 2 diabetic patients. Weight loss will be prevented in order to ascertain the effect of liraglutide alone.
Aim 2: Quantify M1 and M2 (surface and intracellular markers) polarization via flow cytometry in subcutaneous adipose tissue and peripheral blood mononuclear cells after 12 weeks of liraglutide treatment, during which dietary restrictions are lifted and spontaneous weight loss, as would occur in the clinical setting, is allowed. To eliminate confounding by weight loss, a placebo-treated group will undergo matched dietary weight loss for comparison to the liraglutide group to ascertain whether changes in macrophage polarization at 12 weeks are greater in the liraglutide group.
Aim 3: Quantify macrophage-mediated localized and systemic inflammation by measuring M1/M2-related inflammatory cytokines in adipose tissue and peripheral blood after 4 and 12 weeks administration of liraglutide versus placebo to obese, type 2 diabetic patients.
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 |
|---|---|---|
| Liraglutide group | Experimental | Drug: Victoza (liraglutide) with dietician monitoringDrug with diet control intervention: Subjects assigned to this group receive blinded pens containing liraglutide (commonly known as Victoza), manufactured by Novo Nordisk. Subjects will inject 0.6 mg daily into abdomen during the first week of the study, and if tolerated, will increase dose to 1.2 mg the second week of the study, and then up to 1.8 mg daily from the third week until the end of the 12-week study. Any adverse symptoms as well as fasting blood glucose will be monitored weekly for safety. Subjects, with the guidance of the study's dietitian, will remain weight-stable for the first four weeks of the study, and then will be allowed to lose weight for the remaining eight weeks of the study. |
| Placebo group | Placebo comparator | Other: Placebo with dietician monitoringDiet control-only intervention: Subjects assigned to this group receive blinded pens containing placebo (normal saline) instead of liraglutide (commonly known as Victoza). Subjects will inject 0.6 mg of placebo daily during the first week of the study, will increase to 1.2 mg the second week of the study, and then up to 1.8 mg daily from the third week until the end of the 12-week study. Any adverse symptoms as well as fasting blood glucose will be monitored weekly for safety. Subjects, with the guidance of the study's dietitian, will remain weight-stable for the first four weeks of the study, and then will be allowed to lose weight for the remaining eight weeks of the study. |
Who may qualify
- Ages
- 40 to 69 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- BMI between 25 and 42 kg/m2
- Diet-controlled diabetics, or diabetics on Metformin that have permission from Primacy Care Physician to wash-out of the drug for 6 weeks prior to the study and for the duration of the study
- HbA1C between 6.0 - 7.9 (those on Metformin must have a HbA1c level below 7.5 prior to wash-out period)
- Fasting Blood Glucose < 150 mg/dl
- Women must be post-menopausal or surgically sterile within age range
Key exclusion criteria (15 listed)
- Prior Bariatric surgery
- Personal or family history of medullary thyroid cancer
- MEN2 Syndrome
- Thyroid Nodules (not evaluated by PCP)
- Pancreatitis (acute or chronic)
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 |
|---|---|---|
| Victoza (liraglutide) with dietician monitoringAlso: liraglutideVictoza (liraglutide), an FDA-approved medication, is a glucagon-like peptide-1 (GLP-1) receptor agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Subjects with this intervention will be followed by the MD and dietician throughout the study to monitor progress through 4 week period of weight maintenance and 8 week period of weight loss. | Drug | Liraglutide group |
| Placebo with dietician monitoringSubjects will not receive the study drug, but will be followed by the MD and dietician throughout the study to monitor progress through 4 week period of weight maintenance and 8 week period of weight loss. | Other | Placebo group |
Primary outcome
Macrophage polarization: % M2 macrophages in adipose tissue and peripheral blood according to positivity for cell surface markers (measured by flow cytometry).
Time frame: 30 months
3 secondary outcomes
Inflammation, localized: Pro- and anti-inflammatory cytokines will be measured (IL6, IL-8, TNF-α, MCP-1, cell surface markers, and adiponectin) by rtPCR in adipose tissue and blood macrophages
Time frame: 30 months
Inflammation, systemic: Plasma pro/anti-inflammatory cytokines: IL-6, hsCRP, cell surface markers, and adiponectin will be measured in plasma.
Time frame: 30 months
Macrophage polarization: M1 to M2 ratio in adipose tissue and peripheral blood according to cell surface markers (measured by flow cytometry)
Time frame: 30 months
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 9 Jun 2020.
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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.
Tracey McLaughlin, MD principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Victoza (liraglutide) with dietician monitoring in people with Diabetes Mellitus, Type 2 and Diabetes Mellitus, Type II, run by Stanford University 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 15 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 9 Jun 2020. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Macrophage polarization: % M2 macrophages in adipose tissue and peripheral blood according to positivity for cell surface markers (measured by flow cytometry). (time frame: 30 months). 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 9 Jun 2020; AzTrials last refreshed its copy on 8 Nov 2026.