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

NCT02650206 | Completed Phase 1 FDA Drug

• 1 other identifier: 31063
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus, Type II; Diabetes Mellitus, Adult-Onset; Inflammation

Keywords

diabetes; macrophage; inflammation; adipose tissue; weight loss; liraglutide

Outcome Measures

Primary Outcomes (1)

• Macrophage polarization: % M2 macrophages in adipose tissue and peripheral blood according to positivity for cell surface markers (measured by flow cytometry).

  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

  30 months

• Inflammation, systemic: Plasma pro/anti-inflammatory cytokines: IL-6, hsCRP, cell surface markers, and adiponectin will be measured in plasma.

  30 months

• Macrophage polarization: M1 to M2 ratio in adipose tissue and peripheral blood according to cell surface markers (measured by flow cytometry)

  30 months

Study Arms (2)

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.

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.

Other: Placebo with dietician monitoring

Interventions

Victoza (liraglutide) with dietician monitoring DRUG

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.

Also known as: liraglutide

Liraglutide group

Placebo with dietician monitoring OTHER

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.

Placebo group

Eligibility Criteria

• Age: 40 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Freidenrich Center for Translational Research (FCTR)

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Inflammation; Diabetes Mellitus; Weight Loss

Interventions

Liraglutide

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Body Weight Changes; Body Weight; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Tracey McLaughlin, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine; Division of Endocrinology and Metabolism

Study Record Dates

• First Submitted: June 5, 2015
• First Posted: January 8, 2016
• Study Start: January 1, 2015
• Primary Completion: September 27, 2019
• Study Completion: September 27, 2019
• Last Updated: June 9, 2020

Record last verified: 2020-06

Locations

US (1)