Coronary Microvascular DysfunctionPhase 4NCT02333591
Effect of Intact GLP-1 (7-36) and GLP-1 Metabolite (9-36) on Coronary and Peripheral Vascular Function in Adults
A Phase 4 study testing GlucagonLikePeptide-1 (7-36), GlucagonLikePeptide-1 (9-36) and Saline in people with Coronary Microvascular Dysfunction, run by Mette Zander at 1 site in Denmark.
Trial summary
GLP-1 is an agent for treatment of type 2 diabetes and may have protective effects on the cardiovascular system. The mechanism is complex and there seems to be a dual function with intact GLP-1 (7-36), acting through the GLP-1 receptor, and the GLP-1 (9-36) metabolite acting independently of the GLP-1 receptor. Read more about this study
- Who is it for?
- Ages 35 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Coronary Microvascular Dysfunction
- What is being tested?
- GlucagonLikePeptide-1 (7-36), GlucagonLikePeptide-1 (9-36) and Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 1 siteDenmark
- Study dates
- Jul 2016to Jun 2018
- Phase
- Phase 4
- 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 35 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 35-70 years
- BMI > 25 kg/m2.
- Central obesity (measured by waist circumference, defined as ≥ 94cm for men and ≥ 80 cm for women)
- Non smokers (6 months abstinent is required)
- Normal creatinine
- For fertile women; negative pregnancy test and use of safe anticonception.
- Speak and understand Danish or English
- Mental ability to follow and understand the study
Who cannot join
- Known Diabetes
- Known hypertension (untreated hypertension ≤ 160/100 at inclusion is accepted)
- Haemoglobin < 6.5 mmol/l
- Allergy towards Januvia or Exenatide, Adenosin or Glycerylnitrate
- Documented significant stenosis of the left anterior descending artery (LAD) at coronary angiography or CT-angiography or regional dysfunction documented during dipyridamol stress-echocardiography. If stress test at baseline shows significant stenosis the patient will be excluded from the study.
- Pregnancy
- Severe asthma
- Active cancer, severe co-morbidity with limited life-expectancy, severe hepatic co-morbidity, chronic alcohol abuse, atrial fibrillation, chronic or previous acute pancreatitis, inflammatory bowel disease.
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Department of Research in Endocrinology, Bispebjerg University Hospital
Copenhagen, 2400
About this study
GLP-1 is an agent for treatment of type 2 diabetes and may have protective effects on the cardiovascular system. The mechanism is complex and there seems to be a dual function with intact GLP-1 (7-36), acting through the GLP-1 receptor, and the GLP-1 (9-36) metabolite acting independently of the GLP-1 receptor.
Coronary flow reserve (CFR) is the ratio of flow through the coronary arteries during stress to during rest and it reflects coronary microcirculation. Impaired CFR is a strong predictor of poor prognosis of cardiovascular disease.
The aim of the study is to investigate the acute effects of GLP-1 on coronary microcirculation and endothelial function in adults with obesity.
Read the detailed description
Several studies have shown beneficial effects of glucagon-like-peptide-1 (GLP-1) on the cardiovascular system. Native GLP-1 is secreted from L-cells in the intestine as GLP-1(7-36) 1 but is rapidly metabolised by the ubiquitous enzyme dipeptidyl-peptidase-4 (DPP4) to the metabolite GLP-1(9-36). However, the physiological effect of GLP-1 on the cardiovascular system is complex and there seems to be a dual function with intact GLP-1 (7-36), acting through the GLP-1 receptor, and the GLP-1 (9-36) metabolite acting independently of the GLP-1 receptor.
The aim of the study is to investigate the acute effects of intact GLP-1 and GLP-1 metabolite on coronary microcirculation and endothelial function in adults.
Method 20 adults with obesity are recruited to a double-blind randomized cross-over study.
The first 10 included adults will receive 2½ hours infusion of intact GLP-1 (7-36) together with a DPP-IV inhibitor and 2½ hours infusion of saline, on two separate occasions. The infusions will be given in randomized order with a minimum of 24 hours washout period.
The next 10 included adults will receive 2½ hours infusion of GLP-1 (9-36) metabolite and 2½ hours infusion of saline. These will also be given in randomized order with a minimum of 24 hours washout period. Endothelial function and CFR will be measured before and after one, respectively two, hours of infusion.
The effect of GLP-1 infusions on microvascular function is evaluated by coronary flow reserve (CFR), the ratio between echocardiographic measured coronary flow velocity in LAD during adenosine induced myocardial hyperaemia and rest. The effect on endothelial function is assessed by flow mediated dilation (FMD).
- Conditions
- Coronary Microvascular Dysfunction
- Being tested
- GlucagonLikePeptide-1 (7-36), GlucagonLikePeptide-1 (9-36), Saline
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GlucagonLikePeptide-1 (7-36)Drug
Diluted in saline and human serum albumin, then infused intravenously for 2,5 hours.
GlucagonLikePeptide-1 (9-36)Drug
Diluted in saline and human serum albumin, then infused intravenously for 2,5 hours.
SalineDrug
Also called NaCl, Placebo
Infused intravenously for 2,5 hours.
| Study group | Role | What they receive |
|---|---|---|
| GlucagonLikePeptide-1 (7-36) | Active comparator | GLP-1 (7-36) is diluted in saline and human serum albumin. Plasma levels of GLP-1 (7-36) are rapidly raised and then maintained stable with 5,91 pmol/kg/min (0-2 min) reduced to 2,53 pmol/kg/min (2-4 min) reduced to 2,34 pmol/kg/min (4-6 min) reduced to 2,2 pmol/kg/min (6-8 min) reduced to 2,02 pmol/kg/min (8-10 min) and then maintained stable for 2½ hours with 1.5 pmol/kg/min.
A DPP-IV inhibitor - Januvia 100 mg is given the evening before and ½ an hour before the infusion is started. Receives: Drug: Saline |
| GlucagonLikePeptide-1 (9-36) | Active comparator | GLP-1 (9-36) is diluted in saline and human serum albumin. Plasma levels of GLP-1 (9-36) are rapidly raised and then maintained stable with 5,91 pmol/kg/min (0-2 min) reduced to 2,53 pmol/kg/min (2-4 min) reduced to 2,34 pmol/kg/min (4-6 min) reduced to 2,2 pmol/kg/min (6-8 min) reduced to 2,02 pmol/kg/min (8-10 min) and then maintained stable for 2½ hours with 1.5 pmol/kg/min Receives: Drug: Saline |
| NaCl | Placebo comparator | Saline is infused with a flow rate of 240 ml/h for 10 min and then reduced to 86 ml/h for 2½ hours. Receives: Drug: GlucagonLikePeptide-1 (7-36); Drug: GlucagonLikePeptide-1 (9-36) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Coronary Flow Reserve
Coronary flow reserve (CFR) reflects microvessel coronary function and is the ratio between echocardiographic measured coronary flow velocity in LAD during adenosine induced myocardial hyperaemia and rest.
The outcome is measured at every infusion/intervention (4 times).
Measured: At baseline and after 2 hours of infusion
Secondary outcomes (1)
Endothelial function (Assessed by Flow Mediated Dilation)
Assessed by Flow Mediated Dilation (FMD) The outcome is measured at every infusion/intervention (4 times).
Measured: At baseline and after 1 hour of infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2015 (estimated)
- Study startJul 2016
- Primary completionJun 2018
- Study completionJun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Coronary Microvascular DysfunctionStudies 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 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mette Zander
- Sponsor type
- University, hospital or other
- Collaborators
- Hvidovre University Hospital
- Responsible party
- Sponsor-investigator, Mette Zander, Bispebjerg Hospital
- Investigators
- Mette Zander, PhD, MD, Principal investigator, Department of Endocrinology, Bispebjerg University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02333591
- Sponsor's protocol ID
- MZ02
- Other IDs
- 2013-001240-64
- Status last verified
- Mar 2019
- First submitted
- 6 Jan 2015
- Last updated
- 11 Mar 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Intact GLP-1 (7-36) and GLP-1 Metabolite (9-36) on Coronary and Peripheral Vascular Function in Adults
- ClinicalTrials.gov ID
- NCT02333591
- Acronym / sponsor ID
- MZ02
- Conditions
- Coronary Microvascular Dysfunction
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Mette ZanderUniversity, hospital or other
- Collaborators
- Hvidovre University Hospital
- Study start
- Jul 2016
- Primary completion
- Jun 2018 (actual)
- Study completion
- Jun 2018 (actual)
- First posted
- 7 Jan 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.
GLP-1 is an agent for treatment of type 2 diabetes and may have protective effects on the cardiovascular system. The mechanism is complex and there seems to be a dual function with intact GLP-1 (7-36), acting through the GLP-1 receptor, and the GLP-1 (9-36) metabolite acting independently of the GLP-1 receptor.
Coronary flow reserve (CFR) is the ratio of flow through the coronary arteries during stress to during rest and it reflects coronary microcirculation. Impaired CFR is a strong predictor of poor prognosis of cardiovascular disease.
The aim of the study is to investigate the acute effects of GLP-1 on coronary microcirculation and endothelial function in adults with obesity.
Detailed description
Several studies have shown beneficial effects of glucagon-like-peptide-1 (GLP-1) on the cardiovascular system. Native GLP-1 is secreted from L-cells in the intestine as GLP-1(7-36) 1 but is rapidly metabolised by the ubiquitous enzyme dipeptidyl-peptidase-4 (DPP4) to the metabolite GLP-1(9-36). However, the physiological effect of GLP-1 on the cardiovascular system is complex and there seems to be a dual function with intact GLP-1 (7-36), acting through the GLP-1 receptor, and the GLP-1 (9-36) metabolite acting independently of the GLP-1 receptor.
The aim of the study is to investigate the acute effects of intact GLP-1 and GLP-1 metabolite on coronary microcirculation and endothelial function in adults.
Method 20 adults with obesity are recruited to a double-blind randomized cross-over study.
The first 10 included adults will receive 2½ hours infusion of intact GLP-1 (7-36) together with a DPP-IV inhibitor and 2½ hours infusion of saline, on two separate occasions. The infusions will be given in randomized order with a minimum of 24 hours washout period.
The next 10 included adults will receive 2½ hours infusion of GLP-1 (9-36) metabolite and 2½ hours infusion of saline. These will also be given in randomized order with a minimum of 24 hours washout period. Endothelial function and CFR will be measured before and after one, respectively two, hours of infusion.
The effect of GLP-1 infusions on microvascular function is evaluated by coronary flow reserve (CFR), the ratio between echocardiographic measured coronary flow velocity in LAD during adenosine induced myocardial hyperaemia and rest. The effect on endothelial function is assessed by flow mediated dilation (FMD).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| GlucagonLikePeptide-1 (7-36) | Active comparator | Drug: SalineGLP-1 (7-36) is diluted in saline and human serum albumin. Plasma levels of GLP-1 (7-36) are rapidly raised and then maintained stable with 5,91 pmol/kg/min (0-2 min) reduced to 2,53 pmol/kg/min (2-4 min) reduced to 2,34 pmol/kg/min (4-6 min) reduced to 2,2 pmol/kg/min (6-8 min) reduced to 2,02 pmol/kg/min (8-10 min) and then maintained stable for 2½ hours with 1.5 pmol/kg/min. A DPP-IV inhibitor - Januvia 100 mg is given the evening before and ½ an hour before the infusion is started. |
| GlucagonLikePeptide-1 (9-36) | Active comparator | Drug: SalineGLP-1 (9-36) is diluted in saline and human serum albumin. Plasma levels of GLP-1 (9-36) are rapidly raised and then maintained stable with 5,91 pmol/kg/min (0-2 min) reduced to 2,53 pmol/kg/min (2-4 min) reduced to 2,34 pmol/kg/min (4-6 min) reduced to 2,2 pmol/kg/min (6-8 min) reduced to 2,02 pmol/kg/min (8-10 min) and then maintained stable for 2½ hours with 1.5 pmol/kg/min |
| NaCl | Placebo comparator | Drug: GlucagonLikePeptide-1 (7-36), Drug: GlucagonLikePeptide-1 (9-36)Saline is infused with a flow rate of 240 ml/h for 10 min and then reduced to 86 ml/h for 2½ hours. |
Who may qualify
- Ages
- 35 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age 35-70 years
- BMI > 25 kg/m2.
- Central obesity (measured by waist circumference, defined as ≥ 94cm for men and ≥ 80 cm for women)
- Non smokers (6 months abstinent is required)
- Normal creatinine
Key exclusion criteria (8 listed)
- Known Diabetes
- Known hypertension (untreated hypertension ≤ 160/100 at inclusion is accepted)
- Haemoglobin < 6.5 mmol/l
- Allergy towards Januvia or Exenatide, Adenosin or Glycerylnitrate
- Documented significant stenosis of the left anterior descending artery (LAD) at coronary angiography or CT-angiography or regional dysfunction documented during dipyridamol stress-echocardiography. If stress test at baseline shows significant stenosis the patient will be excluded from the study.
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 |
|---|---|---|
| GlucagonLikePeptide-1 (7-36)Diluted in saline and human serum albumin, then infused intravenously for 2,5 hours. | Drug | NaCl |
| GlucagonLikePeptide-1 (9-36)Diluted in saline and human serum albumin, then infused intravenously for 2,5 hours. | Drug | NaCl |
| SalineAlso: NaCl, PlaceboInfused intravenously for 2,5 hours. | Drug | GlucagonLikePeptide-1 (7-36), GlucagonLikePeptide-1 (9-36) |
Primary outcome
Coronary Flow Reserve
Time frame: At baseline and after 2 hours of infusion
Coronary flow reserve (CFR) reflects microvessel coronary function and is the ratio between echocardiographic measured coronary flow velocity in LAD during adenosine induced myocardial hyperaemia and rest. The outcome is measured at every infusion/intervention (4 times).
1 secondary outcome
Endothelial function (Assessed by Flow Mediated Dilation)
Time frame: At baseline and after 1 hour of infusion
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 11 Mar 2019.
- Individual participant dataSharing planned: Undecided
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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.
Mette Zander, PhD, MD principal investigator
Department of Endocrinology, Bispebjerg University Hospital
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 GlucagonLikePeptide-1 (7-36), GlucagonLikePeptide-1 (9-36) and Saline in people with Coronary Microvascular Dysfunction, run by Mette Zander at 1 site in Denmark.
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 8 inclusion and 8 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 11 Mar 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 Denmark. 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 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?
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?
Coronary Flow Reserve (time frame: At baseline and after 2 hours of infusion). 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 11 Mar 2019.