Effects of Incretins on Human Platelet Function

NCT01408862 | Completed Results

• 1 other identifier: INC-PL-01
• Study Type: observational
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief 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. 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.

Conditions

Inhibition of Platelet Aggregation by Incretins

Keywords

GLP1; GIP; platelets; human; aggregation

Outcome Measures

Primary Outcomes (2)

• 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

  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. 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),

  Platelets drawn from a volunteer will be evaluated 1 time (in 1-2 days)

Study Arms (1)

controls

Healthy volunteers will be asked to donor a 10-80 ml blood through a venous puncture

Other: venous puncture

Interventions

venous puncture OTHER

Blood for in vitro studies will be drawn

Also known as: volunteers

controls

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Healthy subjects

You may qualify if:

• Healthy blood donors

You may not qualify if:

• Diabetes
• Hypertension
• Morbid obesity
• Cardiovascular disease
• Hematological diseases and hyperlipidemia

Sponsors & Collaborators

• National Council of Scientific and Technical Research, Argentina: lead
• Merck Sharp & Dohme LLC: collaborator

Limitations and Caveats

Albeit at high concentrations presumably well above of the physiological range, the use of native and rapidly degradable forms of these peptides may impose a limitation of this study

Results Point of Contact

• Title: Dr. Carlos Jose Pirola
• Organization: Institute of Medical Research (UBA-CONICET)

cpirola@ciudad.com.ar

541145148701

Study Officials

• Carlos J Pirola, PhD

  Unidad Ejecutora IDIM-CONICET

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: observational
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Investigador Superior, Director

Study Record Dates

• First Submitted: August 1, 2011
• First Posted: August 3, 2011
• Study Start: December 1, 2012
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: September 23, 2014
• Results First Posted: September 23, 2014

Record last verified: 2014-09