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Effect of Liraglutide (Victoza) on Inflammation in Human Adipose Tissue and Blood

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ClinicalTrials.gov Identifier: NCT02650206
Recruitment Status : Recruiting
First Posted : January 8, 2016
Last Update Posted : February 13, 2018
Sponsor:
Information provided by (Responsible Party):
Tracey McLaughlin, Stanford University

Brief 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 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.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 Diabetes Mellitus, Type II Diabetes Mellitus, Adult-Onset Inflammation Drug: Victoza (liraglutide) with dietician monitoring Other: Placebo with dietician monitoring Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 56 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Basic Science
Official Title: Effect of Liraglutide on Macrophage Polarization in Human Adipose Tissue and Peripheral Blood
Actual Study Start Date : January 2015
Estimated Primary Completion Date : August 2018
Estimated Study Completion Date : August 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Liraglutide

Arm Intervention/treatment
Experimental: Liraglutide group

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.

Drug: Victoza (liraglutide) with dietician monitoring
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.
Other Name: liraglutide

Placebo Comparator: Placebo group

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.

Other: Placebo with dietician monitoring
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.




Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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 ]
  2. Inflammation, systemic: Plasma pro/anti-inflammatory cytokines: IL-6, hsCRP, cell surface markers, and adiponectin will be measured in plasma. [ Time Frame: 30 months ]
  3. 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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 69 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • Prior Bariatric surgery
  • Personal or family history of medullary thyroid cancer
  • MEN2 Syndrome
  • Thyroid Nodules (not evaluated by PCP)
  • Pancreatitis (acute or chronic)
  • Gallstones
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02650206


Contacts
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Contact: Elizabeth A Colbert, BA 650-736-2056 ecolbert@stanford.edu
Contact: Dalia Perelman, MS 650-736-2056 daliap@stanford.edu

Locations
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United States, California
Freidenrich Center for Translational Research (FCTR) Recruiting
Stanford, California, United States, 94305
Contact: Elizabeth Colbert    650-736-2056    ecolbert@stanford.edu   
Contact: Dalia Perelman    6507362056    daliap@stanford.edu;   
Sponsors and Collaborators
Stanford University
Investigators
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Principal Investigator: Tracey McLaughlin, MD Stanford University

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Responsible Party: Tracey McLaughlin, Associate Professor of Medicine; Division of Endocrinology and Metabolism, Stanford University
ClinicalTrials.gov Identifier: NCT02650206     History of Changes
Other Study ID Numbers: 31063
First Posted: January 8, 2016    Key Record Dates
Last Update Posted: February 13, 2018
Last Verified: February 2018

Keywords provided by Tracey McLaughlin, Stanford University:
diabetes
macrophage
inflammation
adipose tissue
weight loss
liraglutide

Additional relevant MeSH terms:
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Diabetes Mellitus
Inflammation
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pathologic Processes
Liraglutide
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists