Inhibition of Platelet Aggregation by IncretinsNCT01408862
Effects of Incretins on Human Platelet Function
An observational study of Inhibition of Platelet Aggregation by Incretins, run by National Council of Scientific and Technical Research, Argentina.
Trial summary
Novel drugs for the treatment of patients with diabetes are of interest for cardiologists if they reduce the risk of cardiovascular events. However, as documented by the current discussion about the potential benefits of glitazones, high hopes can fail. Read more about this study
- Who is it for?
- Ages 21 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Inhibition of Platelet Aggregation by Incretins
- What is being tested?
- venous puncture
- How many people
- 20 participants
- Where
- No sites listed yet
- Study dates
- Dec 2012to Aug 2014
- Phase
- Observational
- 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 21 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Healthy subjects
Who may be able to join
- Healthy blood donors
Who cannot join
- Diabetes
- Hypertension
- Morbid obesity
- Cardiovascular disease
- Hematological diseases and hyperlipidemia
About this study
Novel drugs for the treatment of patients with diabetes are of interest for cardiologists if they reduce the risk of cardiovascular events. However, as documented by the current discussion about the potential benefits of glitazones, high hopes can fail. Initial beneficial cardiovascular effects shown in proof-of-concept studies were muted by the apparent higher mortality in the metaanalysis of studies with rosiglitazone. The rapidly increasing use of GLP-1 analogues and DPP-4 (Dipeptidyl protease 4) inhibitors for the treatment of type 2 diabetes mellitus may be of major interest for the cardiologist. Potential beneficial actions on the cardiovascular system so far shown in animal experiments and small proof of concept studies may provide the rationale for using these drugs specifically in diabetic patients with secondary complications such as macrovascular disease or diabetic cardiomyopathy. Theoretically, these new therapies could also proof beneficial in patients with heart failure, independently of concomitant diabetes mellitus. However, many unanswered questions need to be addressed in the near future to extend the experimental findings to potential benefits of real life patients. In summary a new class of antidiabetic drugs, which could possibly directly influence cardiovascular effects of diabetes mellitus and thus possibly treat or even prevent life threatening complications has become available.
Then our working hypothesis was that incretins may have desirable cardiovascular outcomes through modulating platelet function. In order to test this hypothesis we propose to assess the presence of their specific receptors in isolated human platelets. In addition, we proposed to sudy the effect of the endogenous incretins (glucagon-like peptide 1 and gastric inhibitory peptide) on human platelet function isolated in a test tube.
Read the detailed description
Aims and Methods: The prevalence of Type 2 diabetes (T2D) continues to increase globally and brings with it a parallel increase in the associated cardiovascular disease complications. Correction of platelet hyperactivity holds promise for this high-risk population of T2D patients by contributing to restore normal hemostasis, which has lead to the search for new antiagregant drugs. Then, our aim was to study whether incretins may modulate platelet function; for this purpose platelets from healthy subjects who were not taken any medication were studied. Besides, normal mature megakaryocytes obtained by culture of human cord blood derived-CD34+ hematopoietic progenitor cells were also studied.
For platelet function studies, platelet aggregation was tested in the absence and presence of different concentrations (10-9 M to 10-5 M) of glucagon-like peptide-1,GLP1-(7-36)NH2, and glucose-dependent insulinotropic polypeptide (GIP) agonist by a turbidimetricassay. The effect of 300 mg/dLglucose added to the media was also evaluated. GLP1R (glucagon-like peptide 1 receptor) and GIPR (GIP receptor) mRNA expression was evaluated by Real Time PCR in platelet and megakaryocyte total mRNA. The putative presence of their proteins was assayed by western blot and flow cytometry in both samples.
- Being tested
- venous puncture
- Keywords
- GLP1, GIP, platelets, human, aggregation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
venous punctureOther
Also called volunteers
Blood for in vitro studies will be drawn
| Study group | Role | What they receive |
|---|---|---|
| controls | Healthy volunteers will be asked to donor a 10-80 ml blood through a venous puncture Receives: Other: venous puncture |
What is being measured
The primary outcome is the main question the study is designed to answer.
Expression of Glucagon Like Peptide -1 (GLP-1) and Gastric Inhibitory Peptide (GIP) Receptors in Normal Human Platelets
1.1 Measurement of GLP-1 and GIP receptors at the platelet RNA level by Real Time-PCR 1.2 GLP-1 and GIP receptors detection at the protein level: 1.2.1 Expression on platelet membrane by flow cytometry. 1.2.2 Detection in total platelet proteins by western-blot. Data of flow cytometry are provided below
Measured: Platelets drawn from a volunteer were evaluated 1 time (in 1-2 days)
Changes in Basal or Aggregant-induced Platelet Activation (With and Without Glucose Added to the Media, 200 mg/dl, 400 mg/dL) by GLP-1-(7-36)NH2 and Its Metabolite (GLP-1-(9-36)NH2)and a GIP Agonist at Different Concentrations.
1 Direct effect of GLP-1-(7-36)NH2 and its metabolite (GLP-1-(9-36)NH2) and GIP agonist on platelet aggregation, with and without preincubation at different glucose concentrations.
- GLP-1-(7-36)NH2 and its metabolite (GLP-1-(9-36)NH2) and GIP agonist modulation (with and without 300 mg/dL glucose added to the media) of platelet activation and aggregation induced by classical platelet agonists such as ADP, collagen and bovine von Willebrand factor.
Data points from various conditions were combined (averaged),
Measured: Platelets drawn from a volunteer will be evaluated 1 time (in 1-2 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2011 (estimated)
- Study startDec 2012
- Primary completionAug 2014
- Study completionAug 2014
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 Inhibition of Platelet Aggregation by IncretinsStudies 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
- Observational
- Time perspective
- Cross-sectional
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Council of Scientific and Technical Research, Argentina
- Sponsor type
- Other government
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Carlos Jose Pirola, National Council of Scientific and Technical Research, Argentina
- Investigators
- Carlos J Pirola, PhD, Principal investigator, Unidad Ejecutora IDIM-CONICET
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01408862
- Sponsor's protocol ID
- INC-PL-01
- Status last verified
- Sep 2014
- First submitted
- 1 Aug 2011
- Last updated
- 23 Sep 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Incretins on Human Platelet Function
- ClinicalTrials.gov ID
- NCT01408862
- Acronym / sponsor ID
- INC-PL-01
- Keywords
- GLP1, GIP, platelets, human, aggregation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- National Council of Scientific and Technical Research, ArgentinaOther government
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Dec 2012
- Primary completion
- Aug 2014 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 3 Aug 2011 (estimated)
- Results
- Posted 23 Sep 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Novel drugs for the treatment of patients with diabetes are of interest for cardiologists if they reduce the risk of cardiovascular events. However, as documented by the current discussion about the potential benefits of glitazones, high hopes can fail. Initial beneficial cardiovascular effects shown in proof-of-concept studies were muted by the apparent higher mortality in the metaanalysis of studies with rosiglitazone. The rapidly increasing use of GLP-1 analogues and DPP-4 (Dipeptidyl protease 4) inhibitors for the treatment of type 2 diabetes mellitus may be of major interest for the cardiologist. Potential beneficial actions on the cardiovascular system so far shown in animal experiments and small proof of concept studies may provide the rationale for using these drugs specifically in diabetic patients with secondary complications such as macrovascular disease or diabetic cardiomyopathy. Theoretically, these new therapies could also proof beneficial in patients with heart failure, independently of concomitant diabetes mellitus. However, many unanswered questions need to be addressed in the near future to extend the experimental findings to potential benefits of real life patients. In summary a new class of antidiabetic drugs, which could possibly directly influence cardiovascular effects of diabetes mellitus and thus possibly treat or even prevent life threatening complications has become available.
Then our working hypothesis was that incretins may have desirable cardiovascular outcomes through modulating platelet function. In order to test this hypothesis we propose to assess the presence of their specific receptors in isolated human platelets. In addition, we proposed to sudy the effect of the endogenous incretins (glucagon-like peptide 1 and gastric inhibitory peptide) on human platelet function isolated in a test tube.
Detailed description
Aims and Methods: The prevalence of Type 2 diabetes (T2D) continues to increase globally and brings with it a parallel increase in the associated cardiovascular disease complications. Correction of platelet hyperactivity holds promise for this high-risk population of T2D patients by contributing to restore normal hemostasis, which has lead to the search for new antiagregant drugs. Then, our aim was to study whether incretins may modulate platelet function; for this purpose platelets from healthy subjects who were not taken any medication were studied. Besides, normal mature megakaryocytes obtained by culture of human cord blood derived-CD34+ hematopoietic progenitor cells were also studied.
For platelet function studies, platelet aggregation was tested in the absence and presence of different concentrations (10-9 M to 10-5 M) of glucagon-like peptide-1,GLP1-(7-36)NH2, and glucose-dependent insulinotropic polypeptide (GIP) agonist by a turbidimetricassay. The effect of 300 mg/dLglucose added to the media was also evaluated. GLP1R (glucagon-like peptide 1 receptor) and GIPR (GIP receptor) mRNA expression was evaluated by Real Time PCR in platelet and megakaryocyte total mRNA. The putative presence of their proteins was assayed by western blot and flow cytometry in both samples.
Study design
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| controls | – | Other: venous punctureHealthy volunteers will be asked to donor a 10-80 ml blood through a venous puncture |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Healthy subjects
Key inclusion criteria (1 listed)
- Healthy blood donors
Key exclusion criteria (5 listed)
- Diabetes
- Hypertension
- Morbid obesity
- Cardiovascular disease
- Hematological diseases and hyperlipidemia
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 |
|---|---|---|
| venous punctureAlso: volunteersBlood for in vitro studies will be drawn | Other | controls |
Primary outcome
Expression of Glucagon Like Peptide -1 (GLP-1) and Gastric Inhibitory Peptide (GIP) Receptors in Normal Human Platelets
Time frame: Platelets drawn from a volunteer were evaluated 1 time (in 1-2 days)
1.1 Measurement of GLP-1 and GIP receptors at the platelet RNA level by Real Time-PCR 1.2 GLP-1 and GIP receptors detection at the protein level: 1.2.1 Expression on platelet membrane by flow cytometry. 1.2.2 Detection in total platelet proteins by western-blot. Data of flow cytometry are provided below
Changes in Basal or Aggregant-induced Platelet Activation (With and Without Glucose Added to the Media, 200 mg/dl, 400 mg/dL) by GLP-1-(7-36)NH2 and Its Metabolite (GLP-1-(9-36)NH2)and a GIP Agonist at Different Concentrations.
Time frame: Platelets drawn from a volunteer will be evaluated 1 time (in 1-2 days)
1 Direct effect of GLP-1-(7-36)NH2 and its metabolite (GLP-1-(9-36)NH2) and GIP agonist on platelet aggregation, with and without preincubation at different glucose concentrations. 2. GLP-1-(7-36)NH2 and its metabolite (GLP-1-(9-36)NH2) and GIP agonist modulation (with and without 300 mg/dL glucose added to the media) of platelet activation and aggregation induced by classical platelet agonists such as ADP, collagen and bovine von Willebrand factor. Data points from various conditions were combined (averaged),
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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.
Carlos J Pirola, PhD principal investigator
Unidad Ejecutora IDIM-CONICET
Questions about this trial
What is this clinical trial studying?
An observational study of Inhibition of Platelet Aggregation by Incretins, run by National Council of Scientific and Technical Research, Argentina.
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 1 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 23 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Sep 2014). 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?
Expression of Glucagon Like Peptide -1 (GLP-1) and Gastric Inhibitory Peptide (GIP) Receptors in Normal Human Platelets (time frame: Platelets drawn from a volunteer were evaluated 1 time (in 1-2 days)). The study lists 2 primary outcomes in all. 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 23 Sep 2014.