Effects of Saxagliptin on Adipose Tissue Inflammation in Humans

Sponsor

Phoenix VA Health Care System (U.S. Fed)

Overall Status

Completed

CT.gov ID

NCT02285985

Collaborator

Bristol-Myers Squibb (Industry)

103

Enrollment

Location

Arms

80.3

Actual Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus (T2DM)	Drug: Saxagliptin Drug: Placebo	Phase 4

Detailed Description

This is a randomized, prospective, double-blind study. Randomization to Saxagliptin and placebo will be in a 2:1 fashion. Treatment duration will be approximately 6 weeks.

Study Design

Study Type:

Interventional

Actual Enrollment :

103 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Effects of Saxagliptin on Adipose Tissue Inflammation in Humans

Actual Study Start Date :

Feb 1, 2013

Actual Primary Completion Date :

Oct 12, 2019

Actual Study Completion Date :

Oct 12, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Saxagliptin 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 Tablets: 5 mg Other Names: ONGLYZA™ Inhibitor
Placebo Comparator: Placebo Sugar pill	Drug: Placebo Tablets: 5mg Other Names: Sugar pill

Arm

Intervention/Treatment

Experimental: Saxagliptin

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

Tablets: 5 mg

Other Names:

ONGLYZA™

Inhibitor

Placebo Comparator: Placebo

Sugar pill

Drug: Placebo

Tablets: 5mg

Other Names:

Sugar pill

Outcome Measures

Primary Outcome Measures

Change from baseline in the secretion of cytokines/adipokines by adipose tissue [6 weeks]
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

Secondary Outcome Measures

reduction from baseline in tissue measures of inflammation [6 weeks]
The secondary objective is to determine whether 6 weeks of treatment with saxagliptin, compared to placebo, causes a reduction from baseline in reactive oxygen production, pro-inflammatory gene expression, toll-like receptor and nuclear factor-kappa B activation, and macrophage infiltration in adipose tissue of obese individuals
change in plasma postprandial lipids [6 weeks]
We will also compare the change in postprandial lipids following a standard meal between placebo and saxagliptin
change in reactive hyperemic index [6 weeks]
We will use peripheral artery tonometry to measure the change in endothelial function by measuring reactive hyperemic index

Other Outcome Measures

change in percent arteriole dilation [6 weeks]
Using arterioles isolated from tissue biopsies, we will measure dose related responses to distinct dilators

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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
Additional Laboratory Test Findings
Hemoglobin <12 g/dl in men, <11 g/dl in women
Abnormal prothrombin or partial thromboplastin time
Clinically abnormal thyroid stimulating hormone (TSH)
2 hour glucose > 170mg/dl in standard oral glucose tolerance test (OGTT)
Allergies and Adverse Drug Reactions

Subjects with a history of a serious hypersensitivity reaction to saxagliptin, such as anaphylaxis, angioedema,or exfoliative skin conditions.

Prohibited Treatments and/or Therapies
Treatment with strong systemic cytochrome P450 3A4/5 (CYP 3A4/5) inhibitors
Treatment with any of the following medications during screening or their expected use during the study: recent systemic glucocorticoids (for more than 2 weeks), any anti-hyperglycemic agents, antineoplastic agents, transplant medications, drugs for weight loss, niacin, fibrates, or anti-retroviral medications
Treatment with beta-blockers, antihistamines or inhaled corticosteroids within 3 months prior to screening
Start or change of hormonal replacement therapy within 3 months prior to screening
Other Exclusion Criteria
Prisoners, or subjects who are involuntarily incarcerated
Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness
Currently abusing alcohol or drugs, or have a history of alcohol or drug abuse that in the investigator's opinion could cause the subject to be non-compliant; or have a general history of non-compliance with medications
Any acute febrile illness within 2 weeks of screening with a temperature 100°F