Impact of Hypoglycaemia in Patients With Diabetes Mellitus Type 2 on Platelet Activation

NCT03460899 | Completed Results DMC

• 1 other identifier: HS-2017-04
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

This experimental study is planned to investigate the impact of hypoglycaemia on platelet activation parameters (PAP) during a hyperinsulinaemic hypoglycaemic clamp study. The hypothesis that hypoglycaemia in patients with Diabetes Mellitus, Type 2 (T2DM) leads to increased platelet activation will be tested.

Conditions

Diabetes Mellitus With Hypoglycemia; Diabetes Mellitus, Type 2; Hypoglycemia; Hypoglycemic Episode

Keywords

Hypoglycaemia; Platelet activity; Type 2 diabetes mellitus

Outcome Measures

Primary Outcomes (1)

• Changes in Platelet Activation Marker Adenosin Diphosphate (%)

  Changes in platelet activation measured by light transmittance aggregometry (LTA) on a Chronolog 700 Lumi-Aggregometer based on Adenosin Diphosphate (ADP %) activation. Visit 3, Hyperinsulinaemic/Hypoglycaemic clamp Experiment: Timepoint 0 (Baseline = Plasma Glucose 100mg/dL \[5.5mmol/L\]) Timepoint 1 (Hypoglycaemia Plateau 1 = Plasma Glucose 63mg/dL \[3.5mmol/L\]) Timepoint 2 (Hypoglycaemia Plateau 2 = Plasma Glucose 45mg/dL \[2.5mmol/L\]) Timepoint 3 (Recovery = Plasma Glucose 100mg/dL \[5.5mmol/L\] Follow up 1 (1 Day after the Clamp Experiment) Follow up 2 (7 +/- 1 day after the Clamp Experiment)

  Measurement during different levels of hypoglycaemia as well as 1 and 7 days after the clamp experiment

Secondary Outcomes (3)

• Quantification of Platelet Function and Activation PAC1CD62PCD63POS (%)

  Measurement during different levels of hypoglycaemia as well as 1 and 7 days after the clamp experiment

• Markers of Coagulation Plasminogen Activator Inhibitor-1 (ng/mL)

  Measurement during different levels of hypoglycaemia as well as 1 and 7 days after the clamp experiment

• Changes in Coagulation Marker Fibrinogen (g/L)

  Measurement during different levels of hypoglycaemia as well as 1 and 7 days after the clamp experiment

Study Arms (1)

Clamp Arm

EXPERIMENTAL

All 14 subjects will undergo an Euglycaemic Clamp at Visit 2 as well as a Hyperinsulinaemic/Hypoglycaemic Clamp at Visit 3 with the Intervention of reaching certain plasma glucose levels for blood sampling regarding platelet activity parameters. Infusion of Dextrose and human soluble insulin (Actrapid) will be used to reach certain plasma glucose levels.

Other: Euglycaemic Clamp; Other: Hyperinsulinaemic/Hypoglycaemic Clamp

Interventions

Euglycaemic Clamp OTHER

All 14 subjects will undergo an euglycaemic clamp at Visit 2 with a plasma Glucose target of 5.5 mmol/L +/- 10% (4 timepoints for platelet activity parameter blood sampling)

Clamp Arm

Hyperinsulinaemic/Hypoglycaemic Clamp OTHER

All 14 subjects will undergo a hypoglycaemic/hyperinsulinaemic clamp at Visit 3 with 4 timepoints for platelet activity Parameter blood sampling 30 minutes after reaching certain plasma glucose plateaus (5.5 mmol/L; 3.5 mmol/L; 2.5 mmol/L; after recovery again at 5.5 mmol/L)

Clamp Arm

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female aged 18-64 years (both inclusive) at the time of signing informed consent
• Subjects diagnosed with type 2 diabetes (diagnosed regarding world health organization \[WHO\] criteria) and on stable treatment for a period of 90 days prior to screening with metformin as monotherapy or diet only. Stable is defined as unchanged dose
• Body mass index (BMI) between 20.0 and 35.0 kg/m2 (both inclusive)
• HbA1c between 43 and 64 mmol/mol (6.0% - 8.0%) (both inclusive)
• No use of platelet inhibiting therapy (e.g. aspirin, clopidogrel, ticagrelor, prasugrel)

You may not qualify if:

• All other forms of diabetes (type 1 diabetes, gestational diabetes) than type 2 diabetes mellitus
• Treatment with any glucose lowering agent(s) other than metformin in a period of 60 days before screening. An exception is short-term treatment (≤ 7 days in total) with insulin due to intercurrent illness
• Impaired hypoglycaemic awareness determined at the discretion of the investigator
• Medical history of arrhythmia as atrial fibrillation, atrial flutter, atrioventricular dissociation disorders or ventricular arrhythmias
• Previously known cardiovascular disease and / or past cardiovascular events, or past episodes of a congestive heart failure syndrome (NYHA II - NYHA IV)
• Severe hypoglycaemic event requiring third party help in the last 6 months
• Known allergy to human insulin or dextrose solution
• Clinically significant abnormal haematology, biochemistry, lipids, hormones, coagulation or urinalysis
• Uncontrolled hypertension defined as resting blood pressure at screening (after resting for 5 min, measured in sitting position) outside the range of 90-160 mmHg for systolic or 50-100 mmHg for diastolic
• Chronic liver failure with severe liver dysfunction as assessed by the investigator
• Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) levels \> 3x upper Limit of normal (ULN)
• estimated Glomerular Filtration Rate (eGFR) \<45 ml/min/1,73 m2
• Any musculoskeletal disorders holding back from stay in bed in a lying position during the time of the clamp experiments
• Treatment with beta-blockers, antiarrhythmic agents or neuroleptic drugs
• Active smoker or intake of illicit substances

Sponsors & Collaborators

• Medical University of Graz: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Medical University of Graz, Department for Internal Medicine

Graz, 8036, Austria

Location

Related Publications (1)

• Eyileten C, Wicik Z, Keshwani D, Aziz F, Aberer F, Pferschy PN, Tripolt NJ, Sourij C, Prietl B, Pruller F, von Lewinski D, De Rosa S, Siller-Matula JM, Postula M, Sourij H. Alteration of circulating platelet-related and diabetes-related microRNAs in individuals with type 2 diabetes mellitus: a stepwise hypoglycaemic clamp study. Cardiovasc Diabetol. 2022 May 20;21(1):79. doi: 10.1186/s12933-022-01517-5.

  PMID: 35596173 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Hypoglycemia

Interventions

Glucose Clamp Technique

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Chemistry Techniques, Analytical; Investigative Techniques

Limitations and Caveats

14 subjects could be considered a small patient Group. Given the delayed activation of platelet and coagulation markers in our study, we still can not answer the question, at which glycaemic threshold this activation occurs.

Results Point of Contact

• Title: Assoc.-Prof. Harald Sourij, MD
• Organization: Medical University of Graz

ha.sourij@medunigraz.at

0043 316 385

Study Officials

• Harald Sourij

  Medical University of Graz, Division of Endocrinology and Diabetology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2018
• First Posted: March 9, 2018
• Study Start: February 12, 2018
• Primary Completion: June 11, 2018
• Study Completion: June 11, 2018
• Last Updated: November 18, 2019
• Results First Posted: November 18, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)