NCT02576288

Brief Summary

Abdominal obesity is a major risk factor for heart attack, stroke, peripheral vascular disease, dementia, cancer and Type 2 diabetes. The central hypothesis for this proposal is that pro-atherogenic mediators emanate from inflammation in deep subcutaneous adipose tissue (dSAT) that are released into the systemic circulation and damage the arterial vasculature. The investigators postulate that inflammation of dSAT, when quantified by macrophage phenotyping/enumeration will be a) closely linked with systemic levels of pro-atherogenic mediators and b) tightly associated with endothelial dysfunction and loss of central arterial elasticity, which are highly predictive of future cardiovascular disease (CVD) complications. These relationships provide the basis for macrophage-targeted therapy to reduce obesity-related inflammation and impaired arterial vasoreactivity. The investigators will evaluate a novel approach using a dipeptidyl peptidase 4 inhibitor (DPP4i) sitagliptin, which blocks signal transduction for monocyte/macrophage activation. Thus, in abdominally obese, 18-40 years-old adults without clinical CVD, the show study is expected to show that sitagliptin versus placebo will:

  1. 1.significantly improve early measures of arterial damage (brachial artery endothelial dysfunction and reduced carotid elasticity).
  2. 2.significantly attenuate inflammation in dSAT and local production of pro-inflammatory mediators in adipose tissue, which will be associated with decreases in systemic pro-atherogenic mediators that contribute to atherogenesis.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
21

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Jan 2016

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 12, 2015

Completed
3 days until next milestone

First Posted

Study publicly available on registry

October 15, 2015

Completed
3 months until next milestone

Study Start

First participant enrolled

January 1, 2016

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2017

Completed
Last Updated

July 17, 2019

Status Verified

July 1, 2019

Enrollment Period

2 years

First QC Date

October 12, 2015

Last Update Submit

July 12, 2019

Conditions

AtherosclerosisInflammation

Keywords

SitagliptinBrachial artery flow mediated dilationCarotid stiffnessPro-inflammatoryPro-atherogenicM1 macrophages

Outcome Measures

Primary Outcomes (1)

  • Ultrasound quantification of change in brachial artery flow mediated dilation and carotid stiffness (elasticity and distensibility)

    To ascertain effects of sitagliptin vs placebo on endothelial function (brachial artery flow) and structural measure of atherosclerosis (carotid stiffness)

    Immediately before and after 28 days of study thearpy

Secondary Outcomes (1)

  • Deep subcutaneous adipose tissue inflammation

    Immediately before and after 28 days of study thearpy

Other Outcomes (1)

  • Systemic markers of inflammation/atherogenic mediators and insulin resistance

    Immediately before and after 28 days of study thearpy

Study Arms (2)

Sitagliptin

EXPERIMENTAL

100mg will be administered by mouth daily for 28days

Drug: Sitagliptin

Matching Placebo

PLACEBO COMPARATOR

One placebo will be administered by mouth daily for 28days

Drug: Placebo

Interventions

SitagliptinDRUG

anti-inflammatory properties

Also known as: Januvia
Sitagliptin
PlaceboDRUG

No anti-inflammatory properties

Also known as: Dummy pill
Matching Placebo

Eligibility Criteria

Age18 Years - 40 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • abdominal obesity (≥102cm for men and ≥88cm for women)
  • impaired glucose tolerance with fasting plasma glucose 100-125 or HgbA1C 5.7-6.4%
  • insulin resistance with HOMA-IR ≥3.0
  • stable weight with no change \>3% in prior 6 months

You may not qualify if:

  • regular use of non-steroidal anti-inflammatory drug and unwilling to stop
  • on statin or other anti-inflammatory medication or herbal remedy
  • diabetes or clinically evident cardiovascular disease
  • smoking daily or consuming \>200g of alcohol daily
  • active renal, hepatic, rheumatological or infectious disorder within 28 days

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Southern California Health Sciences Campus

Los Angeles, California, 90033, United States

Location

MeSH Terms

Conditions

AtherosclerosisInflammation

Interventions

Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

ArteriosclerosisArterial Occlusive DiseasesVascular DiseasesCardiovascular DiseasesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

TriazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPyrazines

Study Officials

  • Fred Sattler, MD

    University of Southern California

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Medicine

Study Record Dates

First Submitted

October 12, 2015

First Posted

October 15, 2015

Study Start

January 1, 2016

Primary Completion

December 31, 2017

Study Completion

December 31, 2017

Last Updated

July 17, 2019

Record last verified: 2019-07

Locations

US(1)