Effects of Saxagliptin on Adipose Tissue Inflammation in Humans

NCT02285985 | Completed Phase 4

• 2 other identifiers: 0320086
• Study Type: interventional
• Target: 103
• Locations: 1 country
• Sites: 1

Brief Summary

In this research study, Investigators will be comparing the effects of a medication Saxagliptin versus placebo (a similar looking pill that contains no medication) on inflammation in the body. Research Hypothesis DPP-4 inhibition by saxagliptin (ONGLYZA™) reduces adipose tissue inflammation in obese individuals and this is characterized by decreases in a) reactive oxygen species (ROS) production, b) toll-like receptors (TLR) and NF-kappa B pathway activation, c) expression of pro-inflammatory genes, d) macrophage infiltration, and e) secretion of pro-inflammatory factors.

Conditions

Type 2 Diabetes Mellitus (T2DM)

Keywords

Adipose tissue; Inflammation; .Obesity

Outcome Measures

Primary Outcomes (1)

• Change from baseline in the secretion of cytokines/adipokines by adipose tissue

  The primary objective is to determine whether 6 weeks of treatment with saxagliptin, compared to placebo, causes a reduction from baseline in the production and secretion of cytokines/adipokines by adipose tissue

  6 weeks

Secondary Outcomes (3)

• reduction from baseline in tissue measures of inflammation

  6 weeks

• change in plasma postprandial lipids

  6 weeks

• change in reactive hyperemic index

  6 weeks

Other Outcomes (1)

• change in percent arteriole dilation

  6 weeks

Study Arms (2)

Saxagliptin

EXPERIMENTAL

Saxagliptin (trade-name ONGLYZA™) is used along with diet and exercise to lower blood sugar levels in patients with Type II diabetes (condition in which blood sugar is too high because the body does not produce or use insulin normally). Saxagliptin is in a class of medications called dipeptidyl peptidase-4 (DPP-4) inhibitors. It works by increasing the amount of insulin produced by the body after meals when blood sugar is high As the blood sugar returns towards normal, the medication effect on insulin is decreased.

Drug: Saxagliptin

Placebo

PLACEBO COMPARATOR

Sugar pill

Drug: Placebo

Interventions

Saxagliptin DRUG

Tablets: 5 mg

Also known as: ONGLYZA™, Inhibitor

Saxagliptin

Placebo DRUG

Tablets: 5mg

Also known as: Sugar pill

Placebo

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Written Informed Consent
• Before any study procedures are performed, subjects will have the details of the study described to them, and they will be given a written informed consent document to read. Then, if subjects consent to participate in the study, they will indicate that consent by signing and dating the informed consent document in the presence of study personnel.
• Subjects must be able to communicate meaningfully with the investigator and legally competent to provide informed written consent.
• Target Population
• Body mass index 27.5-37.5 kg/m2
• Stable body weight (not varying \>10% during the last 6 months)
• Age and Reproductive Status
• Men and women, ages 21 to 70 years.
• Women must be sterilized by hysterectomy or postmenopausal or on acceptable birth control if of childbearing potential.
• Women of childbearing potential (WOCBP) include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal. Post menopause is defined as:
• Amenorrhea ≥12 consecutive months without another cause and a documented serum follicle stimulating hormone (FSH) level \>35 mIU/mL, or
• Women with irregular menstrual periods and a documented serum FSH level \>35 mIU/mL, or NOTE: FSH level testing is not required for women ≥62 years old with amenorrhea of ≥1 year
• Women on hormone replacement therapy (HRT) Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (e.g., vasectomy) should be considered to be of childbearing potential.

You may not qualify if:

• Sex and Reproductive Status
• WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period
• Women who are pregnant or breastfeeding
• Target Disease Exceptions
• Gastrointestinal disease (including gastrectomy, chronic pancreatitis, bariatric surgery and gastroparesis)
• Hepatic disease (ALT, AST \>2.5 times the upper limit of normal, high sensitivity CRP ≥1 mg/L)
• Kidney disease (serum creatinine \>1.6 mg/dl, Creatinine Clearance 50 mL/min)
• Hypertension (blood pressure \> 150/95 mmHg) at Screening for the mean of three consecutive readings performed in a sitting position after a 5-minute resting period. If treatment for hypertension has recently been initiated, subjects must be clinically stable for 4 weeks prior to Screening
• Cardiac disease (myocardial infarction within past year, clinically significant arrhythmia, unstable angina, congestive heart failure, or coronary artery bypass surgery within 1 year or expected to require coronary bypass surgery within 12 months of study entry).
• Medical History and Concurrent Diseases
• Type 1 diabetes mellitus
• Type 2 diabetes mellitus
• History of diabetic ketoacidosis or hyperosmolar nonketotic coma
• Malignancy other than basal cell or squamous cell skin cancer
• Significant clinical allergic rhinitis or asthma, regularly requiring inhaled corticosteroids and/or antihistamines

Sponsors & Collaborators

• Phoenix VA Health Care System: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Carl T. Hayden VA Medical Hospital

Phoenix, Arizona, 85012, United States

Location

Related Publications (1)

• Kim SH, Liu A, Ariel D, Abbasi F, Lamendola C, Grove K, Tomasso V, Ochoa H, Reaven G. Effect of salsalate on insulin action, secretion, and clearance in nondiabetic, insulin-resistant individuals: a randomized, placebo-controlled study. Diabetes Care. 2014 Jul;37(7):1944-50. doi: 10.2337/dc13-2977.

  PMID: 24963111 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Inflammation; Obesity

Interventions

saxagliptin; Sugars

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Carbohydrates

Study Officials

• Peter D Reaven, MD

  Carl T. Hayden VA Medical Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2014
• First Posted: November 7, 2014
• Study Start: February 1, 2013
• Primary Completion: October 12, 2019
• Study Completion: October 12, 2019
• Last Updated: July 22, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)