AtherosclerosisPhase 2SAVORONCT02576288
Sitagliptin Effects on Arterial Vasculature and Inflammation in Obesity
A Phase 2 study testing Sitagliptin in people with Atherosclerosis and Inflammation, run by University of Southern California at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Atherosclerosis, Inflammation
- What is being tested?
- Sitagliptin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2016to 31 Dec 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Southern California Health Sciences Campus
Los Angeles, California, 90033
About this study
Official title: Effects of Sitagliptin on Arterial Vasoreactivity and Proatherogenic Mediators in Obesity
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:
- significantly improve early measures of arterial damage (brachial artery endothelial dysfunction and reduced carotid elasticity).
- 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.
Since many obese persons fail to sustain weight loss by lifestyle interventions including diet and exercise, an important public health goal is to identify relatively safe alternative strategies that can be used pre-emptively in "asymptomatic" obese persons when arterial dysfunction and damage is still reversible before atherosclerosis progresses to serious CVD events.
Read the detailed description
APPROACH:
Overview of Study Design: This is a double-masked, randomized, placebo-controlled pilot study of treatment sitagliptin (100mg/day) to suppress monocyte/macrophage activation in obese non-diabetic participants. 16 abdominally obese18-40 year-old largely minorities will be randomized 3:1 to receive sitagliptin (N=12) or matching placebo (N=4) daily for 28 days.
Eligibility Criteria for the Study Cohort: Based on prior studies conducted by the investigators, approximately 60-70% of participants enrolled will be Hispanics and African Americans. Both minorities have increased prevalence of insulin resistance (IR) at young ages. In their prior studies, insulin resistance (HOMA-IR* ≥3.0) had a predictive value of 88% for crown like structure in abdominal fat (a surrogate for fat inflammation); the inclusion criterion for IR will assure that most study subjects will have abdominal fat inflammation.
- homeostatic method of analysis-insulin resistance
Inclusion Criteria
- Age 18-40 years of age
- Stable weight (no change >3% in prior 6 months)
- Waist circumference ≥102cm for men; ≥88cm for women
- Fasting plasma glucose 100-125, HgbA1C 5.7-6.4% or HOMA-IR* ≥3.0
Exclusion Criteria:
- Regular use of a non-steroidal anti-inflammatory drug (NSAID); unwilling to stop NSAID drug
- On statin or other prescription anti-inflammatory drugs
- Diabetes or clinically evident cardiovascular disease
- Smoking daily or consuming >200g alcohol/day
Study participants will be adults 18-40 years of age to exclude older persons with irreversible atherosclerosis (e.g. calcified, stenotic plaque) or subclinical arterial thrombus which release inflammatory mediators. Persons with Type 2 diabetes (a myocardial infarction equivalent) and those receiving "statins" (also potent anti-inflammatory drugs) will be excluded, thereby further excluding participants with advanced atherosclerosis. The goal is to identify and study persons with abdominal obesity and inflammation at a younger age as a potential target population for pre-emptive anti-inflammatory therapy to prevent serious CVD events over ensuing years.
Outcome Measures:
- Change in arterial vasoreactivity measured and quantified by ultrasound assessment of brachial artery flow mediated dilation and carotid stiffness (elasticity and distensibility).
- Change in measures of inflammation in intra-abdominal adipose tissue:
- M1 pro-inflammatory macrophages and M2 anti-inflammatory macrophages by fluorescent activated cell sorting.
- Ex vivo secretion of inflammatory mediators from macrophages fractions.
- Change in systemic pro-inflammatory/pro-atherogenic markers and insulin resistance.
- Conditions
- Atherosclerosis, Inflammation
- Being tested
- Sitagliptin, Placebo
- Keywords
- Sitagliptin, Brachial artery flow mediated dilation, Carotid stiffness, Pro-inflammatory, Pro-atherogenic, M1 macrophages
- Medical subject headings
- Atherosclerosis, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SitagliptinDrug
Also called Januvia
anti-inflammatory properties
PlaceboDrug
Also called Dummy pill
No anti-inflammatory properties
| Study group | Role | What they receive |
|---|---|---|
| Sitagliptin | Experimental | 100mg will be administered by mouth daily for 28days Receives: Drug: Sitagliptin |
| Matching Placebo | Placebo comparator | One placebo will be administered by mouth daily for 28days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: Immediately before and after 28 days of study thearpy
Secondary outcomes (1)
Deep subcutaneous adipose tissue inflammation
quantify M1 and M2 macrophages by fluorescence activated cell sorting and ex vivo secretion of pro-inflammatory mediators
Measured: Immediately before and after 28 days of study thearpy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2015 (estimated)
- Study startJan 2016
- Primary completion31 Dec 2017
- Study completion31 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AtherosclerosisStudies of the same condition, open and under way.
- More trials run by University of Southern CaliforniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Southern California
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Fred Sattler, MD, University of Southern California
- Investigators
- Fred Sattler, MD, Principal investigator, University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02576288
- Sponsor's protocol ID
- HS-13-00345
- Acronym
- SAVORO
- Status last verified
- Jul 2019
- First submitted
- 12 Oct 2015
- Last updated
- 17 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Sitagliptin on Arterial Vasoreactivity and Proatherogenic Mediators in Obesity
- ClinicalTrials.gov ID
- NCT02576288
- Acronym / sponsor ID
- SAVORO / HS-13-00345
- Conditions
- Atherosclerosis, Inflammation
- Keywords
- Sitagliptin, Brachial artery flow mediated dilation, Carotid stiffness, Pro-inflammatory, Pro-atherogenic, M1 macrophages
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- University of Southern CaliforniaUniversity, hospital or other
- Study start
- Jan 2016 (actual)
- Primary completion
- 31 Dec 2017 (actual)
- Study completion
- 31 Dec 2017 (actual)
- First posted
- 15 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- significantly improve early measures of arterial damage (brachial artery endothelial dysfunction and reduced carotid elasticity).
- 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.
Since many obese persons fail to sustain weight loss by lifestyle interventions including diet and exercise, an important public health goal is to identify relatively safe alternative strategies that can be used pre-emptively in "asymptomatic" obese persons when arterial dysfunction and damage is still reversible before atherosclerosis progresses to serious CVD events.
Detailed description
APPROACH:
Overview of Study Design: This is a double-masked, randomized, placebo-controlled pilot study of treatment sitagliptin (100mg/day) to suppress monocyte/macrophage activation in obese non-diabetic participants. 16 abdominally obese18-40 year-old largely minorities will be randomized 3:1 to receive sitagliptin (N=12) or matching placebo (N=4) daily for 28 days.
Eligibility Criteria for the Study Cohort: Based on prior studies conducted by the investigators, approximately 60-70% of participants enrolled will be Hispanics and African Americans. Both minorities have increased prevalence of insulin resistance (IR) at young ages. In their prior studies, insulin resistance (HOMA-IR* ≥3.0) had a predictive value of 88% for crown like structure in abdominal fat (a surrogate for fat inflammation); the inclusion criterion for IR will assure that most study subjects will have abdominal fat inflammation.
- homeostatic method of analysis-insulin resistance
Inclusion Criteria
- Age 18-40 years of age
- Stable weight (no change >3% in prior 6 months)
- Waist circumference ≥102cm for men; ≥88cm for women
- Fasting plasma glucose 100-125, HgbA1C 5.7-6.4% or HOMA-IR* ≥3.0
Exclusion Criteria:
- Regular use of a non-steroidal anti-inflammatory drug (NSAID); unwilling to stop NSAID drug
- On statin or other prescription anti-inflammatory drugs
- Diabetes or clinically evident cardiovascular disease
- Smoking daily or consuming >200g alcohol/day
Study participants will be adults 18-40 years of age to exclude older persons with irreversible atherosclerosis (e.g. calcified, stenotic plaque) or subclinical arterial thrombus which release inflammatory mediators. Persons with Type 2 diabetes (a myocardial infarction equivalent) and those receiving "statins" (also potent anti-inflammatory drugs) will be excluded, thereby further excluding participants with advanced atherosclerosis. The goal is to identify and study persons with abdominal obesity and inflammation at a younger age as a potential target population for pre-emptive anti-inflammatory therapy to prevent serious CVD events over ensuing years.
Outcome Measures:
- Change in arterial vasoreactivity measured and quantified by ultrasound assessment of brachial artery flow mediated dilation and carotid stiffness (elasticity and distensibility).
- Change in measures of inflammation in intra-abdominal adipose tissue:
- M1 pro-inflammatory macrophages and M2 anti-inflammatory macrophages by fluorescent activated cell sorting.
- Ex vivo secretion of inflammatory mediators from macrophages fractions.
- Change in systemic pro-inflammatory/pro-atherogenic markers and insulin resistance.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sitagliptin | Experimental | Drug: Sitagliptin100mg will be administered by mouth daily for 28days |
| Matching Placebo | Placebo comparator | Drug: PlaceboOne placebo will be administered by mouth daily for 28days |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SitagliptinAlso: Januviaanti-inflammatory properties | Drug | Sitagliptin |
| PlaceboAlso: Dummy pillNo anti-inflammatory properties | Drug | Matching Placebo |
Primary outcome
Ultrasound quantification of change in brachial artery flow mediated dilation and carotid stiffness (elasticity and distensibility)
Time frame: Immediately before and after 28 days of study thearpy
To ascertain effects of sitagliptin vs placebo on endothelial function (brachial artery flow) and structural measure of atherosclerosis (carotid stiffness)
1 secondary outcome
Deep subcutaneous adipose tissue inflammation
Time frame: Immediately before and after 28 days of study thearpy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2019.
Related trials for Atherosclerosis
Active, not recruitingPhase 4
Effects of Sequential Therapy With Mexidol® (Intravenous) and Mexidol® FORTE 250 (Oral) on Functional Brain Activity Assessed by Functional Magnetic Resonance Imaging and Biochemical Parameters in Patients With Chronic Cerebral Ischemia: A Comparison of Patients With and Without Metabolic Disorders
Metabolic Abnormalities, Obesity & Overweight
Active, not recruiting
SUCCESS (SelUtion, Safety, effiCaCy, hEalth economicS and promS) PTA Study
Peripheral Artery Disease
Active, not recruitingPhase 3
A Study of Inclisiran to Prevent Cardiovascular Events in High-risk Primary Prevention Patients.
Primary Prevention of Atherosclerotic Cardiovascular Disease
RecruitingPhase 3
Reducing Adverse Vascular Outcomes With Factor XI Inhibition in Adult Participants With Peripheral Artery Disease
Peripheral Artery Disease (PAD)
Recruiting
The THOR IDE Study
Peripheral Artery Disease, Peripheral Artery Stenosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Fred Sattler, MD principal investigator
University of Southern California
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sitagliptin in people with Atherosclerosis and Inflammation, run by University of Southern California at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ultrasound quantification of change in brachial artery flow mediated dilation and carotid stiffness (elasticity and distensibility) (time frame: Immediately before and after 28 days of study thearpy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2019.