ObesityPhase 4NCT03101930

Cardiovascular Effects of GLP-1 Receptor Activation

A Phase 4 study testing Liraglutide, Sitagliptin and hypocaloric diet in people with Obesity and PreDiabetes, run by Vanderbilt University Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This project tests the principle hypothesis that stable glucagon like peptide-1 (GLP-1) analogues have specific GLP1R-dependent beneficial effects on vascular endothelial function, fibrinolysis and inflammation in obesity that exceed the benefits of weight loss, and that genetic or other individual factors that… Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Obesity, PreDiabetes
What is being tested?: Liraglutide, Sitagliptin and hypocaloric diet
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 329 participants
Where: 1 siteUnited States
Study dates: 1 May 2017to 24 Jun 2021
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Men and women,
Age 18 to 65 years, and
FPG (100-125 mg/dL) or, IGT (two-hour plasma glucose 140-199 mg/dL) or, HbA1C 5.7-6.4%
BMI≥30 kg/M2
The ability to provide informed consent before any trial-related activities.

Who cannot join

Diabetes type 1 or type 2, as defined by a FPG of 126 mg/dL or greater, a two-hour plasma glucose of 200 mg/dL or greater, or the use of anti-diabetic medication
Resistant hypertension, defined as hypertension requiring the administration of more than three anti-hypertensive agents including a diuretic to achieve control
Use of spironolactone
Known or suspected allergy to trial medications, excipients, or related products.
Family or personal history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma
Personal history of non-familial medullary thyroid carcinoma

Show all 27Show fewer

History of pancreatitis
Contraindications to study medications, worded specifically as stated in the product's prescribing information
Pregnancy or breast-feeding. Women of child-bearing potential will be required to have undergone tubal ligation or to be using an oral contraceptive or barrier methods of birth control
Subjects who have participated in a weight-reduction program during the last six month or whose weight has increased or decreased more than two kg over the preceding six months
Cardiovascular disease such as myocardial infarction within six months prior to enrollment, presence of angina pectoris, significant arrhythmia, congestive heart failure (left ventricular hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis or hypertrophic cardiomyopathy
Treatment with anticoagulants
History of serious neurologic disease such as cerebral hemorrhage, stroke, or transient ischemic attack
History or presence of immunological or hematological disorders
Diagnosis of asthma requiring regular inhaler use
Clinically significant gastrointestinal impairment that could interfere with drug absorption
Impaired hepatic function (aspartate amino transaminase [AST] and/or alanine amino transaminase [ALT] >3.0 x upper limit of normal range)
Individuals with an eGFR<30 mL/min/1.73 m2 or with a UACR >1000µg/mg, where eGFR is determined by the four-variable Modification of Diet in Renal Disease (MDRD) equation, where serum creatinine is expressed in mg/dL and age in years: eGFR (mL/min/1.73m2)=186 • Scr-1.154 • age-0.203 • (1.212 if black) • (0.742 if female)
Hematocrit <35%
Any underlying or acute disease requiring regular medication which could possibly pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult
Treatment with chronic systemic glucocorticoid therapy (more than 7 consecutive days in 1 month)
Treatment with lithium salts
History of alcohol or drug abuse
Treatment with any investigational drug in the one month preceding the study
Previous randomization in this trial
Mental conditions rendering a subject unable to understand the nature, scope and possible consequences of the study
Inability to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study

Trial locations and contacts

1 site in 1 country.

United States1 site

Vanderbilt University Medical Center
Nashville, Tennessee, 37232

Other trials in United States

About this study

Conditions: Obesity, PreDiabetes
Being tested: Liraglutide, Sitagliptin, hypocaloric diet, Placebos, Exendin (9-39)
Medical subject headings: Obesity, Prediabetic State

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LiraglutideDrug
subcutaneous liraglutide daily
SitagliptinDrug
oral sitagliptin daily
hypocaloric dietOther
Reduced calorie intake to achieve weight loss.
PlacebosDrug
Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39.
Exendin (9-39)Drug
All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment.

Study groups in NCT03101930
Study group	Role	What they receive
liraglutide	Experimental	Subjects in the liraglutide group will receive subcutaneous liraglutide (0.6 mg/d for one week, 1.2 mg/d for one week, and then 1.8 mg/d for 12 weeks) and oral placebo. Receives: Drug: Liraglutide; Drug: Placebos; Drug: Exendin (9-39)
sitagliptin	Active comparator	Subjects in the sitagliptin group will receive subcutaneous placebo daily and sitagliptin 100 mg/d orally for 14 weeks. Receives: Drug: Sitagliptin; Drug: Placebos; Drug: Exendin (9-39)
hypocaloric diet	Active comparator	Subjects in the hypocaloric diet group will be given a caloric goal designed to achieve a weight loss similar to that expected in the liraglutide treatment arm based on his or her resting energy expenditure. Subjects will be provided counseling and written instructions on how to achieve their daily caloric goal, including use of their own mobile phone applications to monitor caloric intake. To assure compliance with the prescribed caloric goal, subjects will meet with the study dietitian every other week for problem solving and review of diet intake logs. Receives: Other: hypocaloric diet; Drug: Placebos; Drug: Exendin (9-39)

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Flow-mediated Dilation
Brachial artery diameter is measured under basal conditions and during reactive hyperemia (Flow Mediated Dilation as %)
Measured: Baseline to 2 and 14 weeks
Urine Albumin-to-creatinine Ratio
Ratio of urine albumin to creatinine in a spot urine collected after overnight rest
Measured: Baseline to 13 weeks
Change in Plasminogen Activator Inhibitor-1
Plasma plasminogen activator inhibitor-1 antigen
Measured: Baseline to 2 and 14 weeks

Secondary outcomes (4)

Blood Pressure
The mean of three systolic blood pressure measurements one minute apart using a oscillometric recording device with patient in supine position
Measured: Baseline, and after 2 weeks and 14 weeks of treatment
Heart Rate
The mean of three measurements with the patient in the supine position
Measured: Baseline, and after 2 weeks and 14 weeks of treatment
Fasting Glucose
Blood glucose collected after overnight fast
Measured: Baseline, and after 2 weeks and 14 weeks of treatment
Fasting Insulin
Plasma insulin collected after overnight fast
Measured: Baseline, and after 2 weeks and 14 weeks of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 May 201724 Jun 2021

First posted5 Apr 2017
Study start1 May 2017
Primary completion24 Jun 2021
Study completion24 Jun 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for ObesityStudies of the same condition, open and under way.
More trials run by Vanderbilt University Medical CenterThe 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 4
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 329 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03101930
Sponsor's protocol ID: IRB# 170213
Status last verified: Sep 2022
First submitted: 27 Mar 2017
Last updated: 18 Oct 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: Data will be made available to researchers who provide a methodologically sound proposal that has been approved by the Vanderbilt Institutional Review Board and the study executive committee.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 18 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Cardiovascular Effects of GLP-1 Receptor Activation
ClinicalTrials.gov ID: NCT03101930
Acronym / sponsor ID: IRB# 170213
Conditions: Obesity, PreDiabetes
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 329 participants (actual)
Lead sponsor: Vanderbilt University Medical CenterUniversity, hospital or other
Collaborators: American Heart Association
Study start: 1 May 2017 (actual)
Primary completion: 24 Jun 2021 (actual)
Study completion: 24 Jun 2021 (actual)
First posted: 5 Apr 2017 (actual)
Results: Posted 16 Aug 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
liraglutide	Experimental	Drug: Liraglutide, Drug: Placebos, Drug: Exendin (9-39)Subjects in the liraglutide group will receive subcutaneous liraglutide (0.6 mg/d for one week, 1.2 mg/d for one week, and then 1.8 mg/d for 12 weeks) and oral placebo.
sitagliptin	Active comparator	Drug: Sitagliptin, Drug: Placebos, Drug: Exendin (9-39)Subjects in the sitagliptin group will receive subcutaneous placebo daily and sitagliptin 100 mg/d orally for 14 weeks.
hypocaloric diet	Active comparator	Other: hypocaloric diet, Drug: Placebos, Drug: Exendin (9-39)Subjects in the hypocaloric diet group will be given a caloric goal designed to achieve a weight loss similar to that expected in the liraglutide treatment arm based on his or her resting energy expenditure. Subjects will be provided counseling and written instructions on how to achieve their daily caloric goal, including use of their own mobile phone applications to monitor caloric intake. To assure compliance with the prescribed caloric goal, subjects will meet with the study dietitian every other week for problem solving and review of diet intake logs.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Men and women,
Age 18 to 65 years, and
FPG (100-125 mg/dL) or, IGT (two-hour plasma glucose 140-199 mg/dL) or, HbA1C 5.7-6.4%
BMI≥30 kg/M2
The ability to provide informed consent before any trial-related activities.

Key exclusion criteria (27 listed)

Diabetes type 1 or type 2, as defined by a FPG of 126 mg/dL or greater, a two-hour plasma glucose of 200 mg/dL or greater, or the use of anti-diabetic medication
Resistant hypertension, defined as hypertension requiring the administration of more than three anti-hypertensive agents including a diuretic to achieve control
Use of spironolactone
Known or suspected allergy to trial medications, excipients, or related products.
Family or personal history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma

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
Liraglutidesubcutaneous liraglutide daily	Drug	liraglutide
Sitagliptinoral sitagliptin daily	Drug	sitagliptin
hypocaloric dietReduced calorie intake to achieve weight loss.	Other	hypocaloric diet
PlacebosSubjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39.	Drug	hypocaloric diet, liraglutide, sitagliptin
Exendin (9-39)All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment.	Drug	hypocaloric diet, liraglutide, sitagliptin

Primary outcome

Change in Flow-mediated Dilation
Time frame: Baseline to 2 and 14 weeks
Brachial artery diameter is measured under basal conditions and during reactive hyperemia (Flow Mediated Dilation as %)
Urine Albumin-to-creatinine Ratio
Time frame: Baseline to 13 weeks
Ratio of urine albumin to creatinine in a spot urine collected after overnight rest
Change in Plasminogen Activator Inhibitor-1
Time frame: Baseline to 2 and 14 weeks
Plasma plasminogen activator inhibitor-1 antigen

4 secondary outcomes

Blood Pressure
Time frame: Baseline, and after 2 weeks and 14 weeks of treatment
Heart Rate
Time frame: Baseline, and after 2 weeks and 14 weeks of treatment
Fasting Glucose
Time frame: Baseline, and after 2 weeks and 14 weeks of treatment
Fasting Insulin
Time frame: Baseline, and after 2 weeks and 14 weeks of treatment

Results and safety

Results posted to the registry on 16 Aug 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Liraglutide	46	44
Sitagliptin	23	22
Hypocaloric Diet	24	22

Primary outcome: Change in Flow-mediated Dilation

Time frame: Baseline to 2 and 14 weeks. Mean (Standard Deviation). Unit: Percentage

Measure	Liraglutide n = 44	Sitagliptin n = 22	Hypocaloric Diet n = 22
Baseline to 2 weeks (Placebo infusion)	0.71 (4.82)	2.06 (6.42)	1.24 (5.09)
Baseline to 2 weeks (Exendin infusion)	0.48 (5.81)	0.13 (4.49)	1.43 (7.09)
Baseline to 14 weeks (Placebo infusion)	1.43 (5.33)	1.59 (5.74)	1.01 (5.38)
Baseline to 14 weeks (Exendin infusion)	1.73 (5.22)	1.42 (5.88)	0.42 (4.28)

Population analysed: Incomplete data due to missed study visits and missing samples in the following time periods/arms (n= number of participants with missing data): * Liraglutide/Placebo: Week 2 (n=5); Week 14 (n=4) * Liraglutide/Exendin: Week 2 (n=11); Week 14 (n=12) * Sitagliptin/Placebo: Week 2 (n=2) * Sitagliptin/Exendin: Week 2 (n=3); Week 14 (n=2) * Diet/Placebo: Week 2 (n=1); Week 14 (n=6) * Diet/Exendin: Week 2 (n=7); Week 14 (n=11)

Primary outcome: Urine Albumin-to-creatinine Ratio

Time frame: Baseline to 13 weeks. Mean (Standard Deviation). Unit: mg/g

Measure	Liraglutide n = 44	Sitagliptin n = 22	Hypocaloric Diet n = 22
Baseline	12.0 (23.6)	7.9 (7.6)	6.3 (3.8)
13 Weeks	10.5 (14.8)	9.2 (10.7)	10.1 (19.4)

Population analysed: Due to missed study visits and missing samples, there is incomplete data for the following arms/time periods: Liraglutide: 2 participants; Diet: 6 participants

Primary outcome: Change in Plasminogen Activator Inhibitor-1

Time frame: Baseline to 2 and 14 weeks. Mean (Standard Deviation). Unit: units/mL

Measure	Liraglutide n = 44	Sitagliptin n = 22	Hypocaloric Diet n = 22
Baseline to 2 weeks	-2.4 (7.8)	-1.3 (8.3)	1.1 (6.9)
Baseline to 14 weeks	-3.7 (8.7)	1.3 (6.3)	-3.6 (6.6)

Population analysed: Due to missed study visits and missing samples, there is incomplete data for the following arms/time periods: Liraglutide: Baseline: 2 participants/Week 14: 3 participants; Sitagliptin: Baseline: 1 participants/Week 14: 1 participants; Diet: Baseline: 3 participants/Week 14: 6 participants

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: After randomization to 14 weeks. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Liraglutide	0 of 46 (0%)	26 of 46 (56.5%)	0 of 46
Sitagliptin	1 of 23 (4.3%)	6 of 23 (26.1%)	0 of 23
Hypocaloric Diet	1 of 24 (4.2%)	6 of 24 (25%)	0 of 24

Limitations and caveats (from the sponsor): Study enrollment and conduct interrupted due to COVID-19 pandemic. Exendin not available for all study participants.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. Data will be made available to researchers who provide a methodologically sound proposal that has been approved by the Vanderbilt Institutional Review Board and the study executive committee.

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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.

James M. Luther, M.D. principal investigator

Vanderbilt University Medical Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Liraglutide, Sitagliptin and hypocaloric diet in people with Obesity and PreDiabetes, run by Vanderbilt University Medical Center 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 5 inclusion and 27 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 18 Oct 2022. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Aug 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Change in Flow-mediated Dilation (time frame: Baseline to 2 and 14 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03101930.

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 18 Oct 2022.