Heart DiseaseNCT01760772
Effect of GLP-1 on Postprandial Lipid Metabolism
A study testing Exendin-9, GLP-1 and saline in people with Heart Disease, run by David Dalessio at 1 site in United States.
Trial summary
Individuals with obesity have an increased risk for heart disease and diabetes. There are current drugs on the market that target the hormone, Glucagon like peptide-1 (GLP-1) to treat diabetes. The investigators want to determine if targeting this hormone will also help people with high cholesterol and triglycerides. Read more about this study
- Who is it for?
- Ages 40 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Heart Disease
- What is being tested?
- Exendin-9, GLP-1 and saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2013to Feb 2015
- Phase
- Interventional
- 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 40 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Aim 1: Healthy, normolipemic men and postmenopausal women; aged 40-60 years; BMI between 25-35
- Aim 2: Men and postmenopausal women after successful vertical sleeve gastrectomy (VSG) surgery and age- and weight-matched non-surgical control men and postmenopausal women; ages between 40-6- years; BMI between 28-35; steady weight for at least 3 months prior to study
Who cannot join
- History or clinical evidence of impaired fasting glucose or diabetes mellitus, myocardial infarction or symptoms of congestive heart failure, history or active liver or renal disease, calculated glomerular filtration rate < 60 mL/min).
- History of extreme dyslipidemia (i.e. familial hypercholesterolemia) or Cardiovascular disease (CVD).
- Fasting plasma total cholesterol > 200 mg/dL and fasting plasma TGs > 150 mg/dL.
- Surgery within 6 months.
- Pregnancy or lactation.
- Anemia defined as hematocrit < 33%.
Show all 21Show fewer
- History of cancer or anorexia nervosa or GI disorders.
- Use of medications that alter insulin sensitivity (i.e. niacin, glucocorticoids, metformin) or lipid metabolism (i.e. statin, niacin, fibrate, ezetimibe).
- Plasma HbA1c > 6.0.
- Fasting glucose > 110 mg/dL
- Electrocardiogram (ECG) abnormalities: evidence of ischemia or arrhythmia.
- History of CVD.
- Fasting plasma total cholesterol > 250 mg/dL and fasting plasma TGs > 300 mg/dL.
- Surgical intervention within 6 months.
- Anemia defined as hematocrit < 33%.
- History of cancer or anorexia nervosa or other major GI disease or surgery.
- Use of medications that alter insulin sensitivity (i.e. niacin, glucocorticoids, metformin) or lipid metabolism (i.e. statin, ezetimibe).
- HbA1c > 6.0.
- Fasting glucose > 110 mg/dL
- Electrocardiogram (ECG) abnormalities: evidence of ischemia or arrhythmia.
- Significant renal, hepatic or pulmonary disease.
Trial locations and contacts
1 site in 1 country.
United States1 site
Veteran's Affairs Clinical Research Unit
Cincinnati, Ohio, 45220
Michelle R Adams, PhD, 513-558-6920, michelle.adams@uc.edu
Michelle R Adams, PhD
About this study
Official title: The Role of GLP-1 in Lipid Metabolism in Healthy Subjects and in Subjects After Bariatric Surgery
Individuals with obesity have an increased risk for heart disease and diabetes. There are current drugs on the market that target the hormone, Glucagon like peptide-1 (GLP-1) to treat diabetes. The investigators want to determine if targeting this hormone will also help people with high cholesterol and triglycerides. In this study, the investigators are looking at the role of GLP-1 in healthy subjects and subjects that have had bariatric surgery.
Read the detailed description
Major consequences of the global pandemic of obesity include cardiovascular disease, type 2 diabetes and dyslipidemia. The dyslipidemia of obesity commonly consists of fasting hypertriglyceridemia with increased plasma very low-density lipoprotein (VLDL), reduced high-density lipoprotein (HDL) and the presence of small, dense low-density lipoprotein (LDL). However, more recently, increased secretion of intestinally derived lipoproteins (LPs) has been recognized as contributing to this dyslipidemic profile and postprandial lipemia has been linked to adverse health outcomes. Glucagon-like peptide-1 (GLP-1), a hormone secreted during meal absorption that plays a key role in the control of plasma glucose has been implicated as a candidate hormone for regulating intestinal lipid metabolism. Studies in rodents demonstrate that treatment with the GLP-1R agonist; exendin-4 (Ex-4) reduced postprandial chylomicron (CM) production and CM-associated cholesterol and triglyceride (TG). Similar results were found in Type 2 diabetes (T2D) subjects treated with Ex-4; in these reports there was a reduction in both intestinally derived LP production and total plasma TG. The objective of this study is to determine whether GLP-1 is involved in the physiologic regulation of postprandial lipid metabolism in healthy women, and to test the hypothesis that the improved lipid parameters found in overweight women who have had bariatric surgery are mediated by GLP-1. The specific aims for this project will 1) determine if either pharmacologic treatment with GLP-1 and/or antagonism of endogenous GLP-1 activity improves postprandial lipid metabolism in healthy subjects and 2) determine the role of elevated postprandial GLP-1 levels on lipid metabolism in obese subjects who have had a sleeve gastrectomy. The investigators will use infusions of synthetic GLP-1 with the native hormone to confirm the lipid-lowering results that have been published using pharmacologic GLP-1 receptor (GLP-1R) agonists. The investigators will also use the GLP-1R antagonist exendin-(9-39) to determine the role of endogenous GLP-1 on lipemia after a test meal. A demonstration that this is a physiologic action would expand the current understanding of lipid metabolism, provide new insight into the effects of bariatric surgery, and allow the design of more refined, mechanistic studies of this process. In addition, the potential for GLP-1R signaling to promote lipid metabolism has direct translational importance in that therapies already exist that could capitalize on this mechanism. Understanding the role of GLP-1R regulation of lipid absorption and clearance could lead to more appropriate targeting of GLP-1 based drugs to specific diabetic patients, i.e. ones with problematic dyslipidemia and higher risk for cardiovascular disease. Moreover, understanding the effects of GLP-1 on plasma lipids could eventually lead to new approaches for treating nondiabetic dyslipidemic persons.
- Conditions
- Heart Disease
- Being tested
- Exendin-9, GLP-1, saline
- Keywords
- heart disease, GLP-1, Exendin-9, postprandial lipids
- Medical subject headings
- Heart Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exendin-9Drug
Also called Synthetic exendin (9-39) injection
Bolus of Ex-9 (7500 pmol/kg) over 1 minute followed by continuous infusion at 750 pmol/kg/min
GLP-1Drug
Also called 7-36 amide
Constant infusion of GLP-1 at 0.3 pmol/kg/min
salineOther
Constant infusion
| Study group | Role | What they receive |
|---|---|---|
| Saline | Placebo comparator | 0.9% saline Receives: Other: saline |
| Exendin-9 (Ex-9) | Experimental | Bolus of Ex-9 (7,500 pmol/kg) followed by a continuous infusion at 750 pmol/kg/min Receives: Drug: Exendin-9 |
| GLP-1 | Experimental | GLP-1 infusion at 0.3 pmol/kg/min Receives: Drug: GLP-1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Postprandial Lipids Levels and Apolipoprotein B (ApoB) Levels in plasma
Total and lipoprotein-associated triglyceride and cholesterol levels in baseline and postprandial plasma.
Total apolipoprotein B48 (ApoB48) and apolipoprotein B100 (ApoB100) levels in baseline and postprandial plasma.
Measured: 2 years
Secondary outcomes (3)
Plasma insulin and glucagon
Plasma insulin and glucagon in the fasting and postprandial periods
Measured: 2 years
Plasma free fatty acid (FFA) and glucose levels
Plasma FFA and glucose levels during the fasting and postprandial state
Measured: 2 years
Plasma d-xylose and acetaminophen levels
Plasma d-xylose and acetaminophen levels as indices of gastric emptying
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2013 (estimated)
- Study startFeb 2013
- Primary completionFeb 2015 (estimated)
- Study completionFeb 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart DiseaseStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- David Dalessio
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, David Dalessio, University of Cincinnati
- Investigators
- Michelle R Adams, PhD, Principal investigator, University of CincinnatiDavid D'Alessio, MD, Principal investigator, University of Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01760772
- Sponsor's protocol ID
- 12-09-20-01
- Status last verified
- Nov 2012
- First submitted
- 17 Nov 2012
- Last updated
- 4 Jan 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of GLP-1 in Lipid Metabolism in Healthy Subjects and in Subjects After Bariatric Surgery
- ClinicalTrials.gov ID
- NCT01760772
- Acronym / sponsor ID
- 12-09-20-01
- Conditions
- Heart Disease
- Keywords
- heart disease, GLP-1, Exendin-9, postprandial lipids
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- David DalessioUniversity, hospital or other
- Study start
- Feb 2013
- Primary completion
- Feb 2015 (estimated)
- Study completion
- Feb 2015 (estimated)
- First posted
- 4 Jan 2013 (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.
Individuals with obesity have an increased risk for heart disease and diabetes. There are current drugs on the market that target the hormone, Glucagon like peptide-1 (GLP-1) to treat diabetes. The investigators want to determine if targeting this hormone will also help people with high cholesterol and triglycerides. In this study, the investigators are looking at the role of GLP-1 in healthy subjects and subjects that have had bariatric surgery.
Detailed description
Major consequences of the global pandemic of obesity include cardiovascular disease, type 2 diabetes and dyslipidemia. The dyslipidemia of obesity commonly consists of fasting hypertriglyceridemia with increased plasma very low-density lipoprotein (VLDL), reduced high-density lipoprotein (HDL) and the presence of small, dense low-density lipoprotein (LDL). However, more recently, increased secretion of intestinally derived lipoproteins (LPs) has been recognized as contributing to this dyslipidemic profile and postprandial lipemia has been linked to adverse health outcomes. Glucagon-like peptide-1 (GLP-1), a hormone secreted during meal absorption that plays a key role in the control of plasma glucose has been implicated as a candidate hormone for regulating intestinal lipid metabolism. Studies in rodents demonstrate that treatment with the GLP-1R agonist; exendin-4 (Ex-4) reduced postprandial chylomicron (CM) production and CM-associated cholesterol and triglyceride (TG). Similar results were found in Type 2 diabetes (T2D) subjects treated with Ex-4; in these reports there was a reduction in both intestinally derived LP production and total plasma TG. The objective of this study is to determine whether GLP-1 is involved in the physiologic regulation of postprandial lipid metabolism in healthy women, and to test the hypothesis that the improved lipid parameters found in overweight women who have had bariatric surgery are mediated by GLP-1. The specific aims for this project will 1) determine if either pharmacologic treatment with GLP-1 and/or antagonism of endogenous GLP-1 activity improves postprandial lipid metabolism in healthy subjects and 2) determine the role of elevated postprandial GLP-1 levels on lipid metabolism in obese subjects who have had a sleeve gastrectomy. The investigators will use infusions of synthetic GLP-1 with the native hormone to confirm the lipid-lowering results that have been published using pharmacologic GLP-1 receptor (GLP-1R) agonists. The investigators will also use the GLP-1R antagonist exendin-(9-39) to determine the role of endogenous GLP-1 on lipemia after a test meal. A demonstration that this is a physiologic action would expand the current understanding of lipid metabolism, provide new insight into the effects of bariatric surgery, and allow the design of more refined, mechanistic studies of this process. In addition, the potential for GLP-1R signaling to promote lipid metabolism has direct translational importance in that therapies already exist that could capitalize on this mechanism. Understanding the role of GLP-1R regulation of lipid absorption and clearance could lead to more appropriate targeting of GLP-1 based drugs to specific diabetic patients, i.e. ones with problematic dyslipidemia and higher risk for cardiovascular disease. Moreover, understanding the effects of GLP-1 on plasma lipids could eventually lead to new approaches for treating nondiabetic dyslipidemic persons.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Saline | Placebo comparator | Other: saline0.9% saline |
| Exendin-9 (Ex-9) | Experimental | Drug: Exendin-9Bolus of Ex-9 (7,500 pmol/kg) followed by a continuous infusion at 750 pmol/kg/min |
| GLP-1 | Experimental | Drug: GLP-1GLP-1 infusion at 0.3 pmol/kg/min |
Who may qualify
- Ages
- 40 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Aim 1: Healthy, normolipemic men and postmenopausal women; aged 40-60 years; BMI between 25-35
- Aim 2: Men and postmenopausal women after successful vertical sleeve gastrectomy (VSG) surgery and age- and weight-matched non-surgical control men and postmenopausal women; ages between 40-6- years; BMI between 28-35; steady weight for at least 3 months prior to study
Key exclusion criteria (21 listed)
- History or clinical evidence of impaired fasting glucose or diabetes mellitus, myocardial infarction or symptoms of congestive heart failure, history or active liver or renal disease, calculated glomerular filtration rate < 60 mL/min).
- History of extreme dyslipidemia (i.e. familial hypercholesterolemia) or Cardiovascular disease (CVD).
- Fasting plasma total cholesterol > 200 mg/dL and fasting plasma TGs > 150 mg/dL.
- Surgery within 6 months.
- Pregnancy or lactation.
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 |
|---|---|---|
| Exendin-9Also: Synthetic exendin (9-39) injectionBolus of Ex-9 (7500 pmol/kg) over 1 minute followed by continuous infusion at 750 pmol/kg/min | Drug | Exendin-9 (Ex-9) |
| GLP-1Also: 7-36 amideConstant infusion of GLP-1 at 0.3 pmol/kg/min | Drug | GLP-1 |
| salineConstant infusion | Other | Saline |
Primary outcome
Postprandial Lipids Levels and Apolipoprotein B (ApoB) Levels in plasma
Time frame: 2 years
Total and lipoprotein-associated triglyceride and cholesterol levels in baseline and postprandial plasma. Total apolipoprotein B48 (ApoB48) and apolipoprotein B100 (ApoB100) levels in baseline and postprandial plasma.
3 secondary outcomes
Plasma insulin and glucagon
Time frame: 2 years
Plasma free fatty acid (FFA) and glucose levels
Time frame: 2 years
Plasma d-xylose and acetaminophen levels
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jan 2013.
Related trials for Heart Disease
Not yet recruiting
Effect of Stress Ball Use During Femoral Arterial Sheath Removal After Coronary Angiography
Femoral Arterial Sheath Removal, Stress Ball
Active, not recruiting
Shockwave™ vs Surgical Endarterectomy for Calcified Severe Common Femoral Artery Stenosis: Comparison of Efficacy, Safety and Long-Term Outcomes
Common Femoral Artery Stenosis, Calcification; Heart
RecruitingObservational study
AI-powered ECG Analysis Using Willem™ Software in High-risk Cardiac Patients (WILLEM)
Cardiomyopathies, Cardiac Arrest
RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life(COREVIVE-HFrEF)
Heart Failure With Reduced Ejection Fraction, Iron Deficiency
Recruiting
Trial of the F2 Filter and Delivery System for Embolic Protection During TAVR
Aortic Stenosis Treated With TAVI, Aortic Diseases
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.
Michelle R Adams, PhD principal investigator
University of Cincinnati
David D'Alessio, MD principal investigator
University of Cincinnati
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Exendin-9, GLP-1 and saline in people with Heart Disease, run by David Dalessio 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 2 inclusion and 21 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: status not confirmed, as of the sponsor's last update on 4 Jan 2013. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Michelle R Adams, PhD (513-558-6920, michelle.adams@uc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Postprandial Lipids Levels and Apolipoprotein B (ApoB) Levels in plasma (time frame: 2 years). 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 4 Jan 2013.