Vascular Function and Biomarker Assessments in Healthy Volunteers and in Patients With Type 2 Diabetes Mellitus

NCT ID: NCT04744636

Last Updated: 2024-07-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-03
• Study Completion Date: 2018-09-15

Brief Summary

The purpose of this study is to evaluate the vascular function and biomarkers in healthy volunteers and type 2 diabetic patients.

Detailed Description

The present interventional study will be performed in 3 groups of healthy volunteers of different ages and in type 2 diabetic patients without an investigational medicinal product administrated.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Healthy volunteers aged of 18-30 years

Group Type: OTHER

Other

Intervention Type: DRUG

Healthy volunteers will be selected within 3 weeks before inclusion (Day 0). The investigations will be performed on 2 days (Day 1 (D1) and Day 2 (D2)): vascular endothelial function assessment and blood collection for biomarker investigation on Day 1 and Case Report Form (CFR) on Day 2.

Then, subjects will be discharged at the end of the last investigation day (Day 2).

All the participants have received two pharmacological agents (NIMP) :

• Acetylcholine : administered subcutaneously (by iontophoresis) to assess maximal vascular endothelial function.
• Adenosine : administered intravenously during MRI for the measurement of CFR.

Healthy volunteers aged of 50-59 years

Group Type: OTHER

Other

Intervention Type: DRUG

Healthy volunteers will be selected within 3 weeks before inclusion (Day 0). The investigations will be performed on 2 days (Day 1 (D1) and Day 2 (D2)): vascular endothelial function assessment and blood collection for biomarker investigation on Day 1 and Case Report Form (CFR) on Day 2.

Then, subjects will be discharged at the end of the last investigation day (Day 2).

All the participants have received two pharmacological agents (NIMP) :

• Acetylcholine : administered subcutaneously (by iontophoresis) to assess maximal vascular endothelial function.
• Adenosine : administered intravenously during MRI for the measurement of CFR.

Healthy volunteers aged of 60-70 years

Group Type: OTHER

Other

Intervention Type: DRUG

Healthy volunteers will be selected within 3 weeks before inclusion (Day 0). The investigations will be performed on 2 days (Day 1 (D1) and Day 2 (D2)): vascular endothelial function assessment and blood collection for biomarker investigation on Day 1 and Case Report Form (CFR) on Day 2.

Then, subjects will be discharged at the end of the last investigation day (Day 2).

All the participants have received two pharmacological agents (NIMP) :

• Acetylcholine : administered subcutaneously (by iontophoresis) to assess maximal vascular endothelial function.
• Adenosine : administered intravenously during MRI for the measurement of CFR.

Type 2 diabetic patients aged of 50-70 years

Group Type: OTHER

Other

Intervention Type: DRUG

Type 2 diabetic patients will be selected within 3 weeks before inclusion (Day 0).

The investigations will be performed on 2 days (Day 1 (D1) and Day 2 (D2)): vascular endothelial function assessment and blood collection for biomarker investigation on Day 1 and CFR on Day 2.

Then, subjects will be discharged at the end of the last investigation day (Day 2).

All the participants have received two pharmacological agents (NIMP):

• Acetylcholine : administered subcutaneously (by iontophoresis) to assess maximal vascular endothelial function.
• Adenosine : administered intravenously during MRI for the measurement of CFR.

Interventions

Other

Healthy volunteers will be selected within 3 weeks before inclusion (Day 0). The investigations will be performed on 2 days (Day 1 (D1) and Day 2 (D2)): vascular endothelial function assessment and blood collection for biomarker investigation on Day 1 and Case Report Form (CFR) on Day 2.

Then, subjects will be discharged at the end of the last investigation day (Day 2).

All the participants have received two pharmacological agents (NIMP) :

• Acetylcholine : administered subcutaneously (by iontophoresis) to assess maximal vascular endothelial function.
• Adenosine : administered intravenously during MRI for the measurement of CFR.

Intervention Type: DRUG

Other

Type 2 diabetic patients will be selected within 3 weeks before inclusion (Day 0).

The investigations will be performed on 2 days (Day 1 (D1) and Day 2 (D2)): vascular endothelial function assessment and blood collection for biomarker investigation on Day 1 and CFR on Day 2.

Then, subjects will be discharged at the end of the last investigation day (Day 2).

All the participants have received two pharmacological agents (NIMP):

• Acetylcholine : administered subcutaneously (by iontophoresis) to assess maximal vascular endothelial function.
• Adenosine : administered intravenously during MRI for the measurement of CFR.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Healthy volunteers:

• Age [18 -30], [50-59] and [60-70] years
• Male and female healthy volunteers, except with skin types 5 and 6
• Body weight ≥ 50 kg and BMI between [18.0 -28.0] kg/m^2 inclusive
• Non or ex-smokers (defined as someone who completely stopped smoking for at least 1 month before the beginning of this study)
• No clinically relevant findings in the medical history and physical examination, especially with regards to cardiovascular system, lung, liver and renal function
• Normal blood and urine laboratory tests

Patients with type 2 diabetes (T2D) mellitus:

• Male and female patients, except with skin types 5 and 6
• Age [50 - 70] years
• BMI ≤35 kg/m2
• T2D patients (according to American Diabetes Association (ADA) criteria i.e. HbA1c > 6.5% or fasting plasma glucose > 126 mg/dL (7.00 mmol/L) or 2-hour glucose ≥ 200mg/dL (11.1mmol/L) after 75g oral glucose or glucose ≥200mg/dL (11.1mmol/L) at any time on two separate occasions (historic values and/or at selection)
• Currently treated with Standards of Medical Care in T2D at stable doses for at least 3 months
• Antihypertensive drugs allowed except beta-blockers and calcium antagonists
• Non or ex-smokers (defined as someone who completely stopped smoking for at least 1 month before the beginning of this study)

Healthy volunteers:

• Unlikely to co-operate in the study,
• Participation in another interventional study, including last study drug intake, at the same time or within the 3 months preceding the selection visit; participation in non-interventional registries or epidemiological studies is allowed,
• Deprived of his freedom by administrative or court order or under guardianship,
• History or evidence of acute or chronic abuse of alcohol consumption of> 21 alcohol units per week for males and >14 units per week for females (1 alcohol unit = 100 mL of 12% wine; = 30 mL of 40% spirits; = 250 mL of 6% beer),
• Positive alcohol breath test,
• Positive cotinine test,
• Known or suspected to be drug-dependent,
• Positive result in urinary screening for drug abuse,
• Pregnancy, breastfeeding or lactating,
• Regular use of prescribed and non-prescribed drugs in the last 60 days before the day of investigations into the study except hormonal contraception (e.g. pill or hormonal intrauterine device (IUD) or hormonal implants or Nuva Ring) (if applicable),
• Any drug intake of prescribed or non-prescribed drugs including over-counter drugs (except acetaminophen), herbal remedies or nutritional supplements such as multivitamins in the 2 weeks before the day of investigations unless the investigator deems this drug intake to be irrelevant for the purpose of this study and that can be temporarily suspended,
• Intake of dipyridamol (contraindicated with adenosine infusion)
• Known hypersensitivity to adenosine injection,
• Any acute or chronic illness or clinically relevant findings (i.e. liver, kidney, cardiovascular diseases) in the selection visit examinations,

Patients with type II diabetes mellitus (T2D):

• Unlikely to co-operate in the study,
• Participation in another interventional study, including last study drug intake, at the same time or within the 3 months preceding the selection visit; participation in non-interventional registries or epidemiological studies is allowed,
• Deprived of his freedom by administrative or court order or under guardianship,
• Unwilling to allow his or her primary care practitioner to be notified of participation in the study and for information on a participant's medical history to be obtained from the general practitioner,
• History or evidence of acute or chronic abuse of alcohol consumption of> 21 alcohol units per week for males and >14 units per week for females (1 alcohol unit = 100 mL of 12% wine; = 30 mL of 40% spirits; = 250 mL of 6% beer),
• Positive alcohol breath test,
• Positive cotinine test,
• Known or suspected to be drug-dependent,
• Positive result in urinary screening for drug abuse,
• Pregnancy, breastfeeding or lactating,
• Intake of dipyridamol (contraindicated with adenosine infusion)
• Known hypersensitivity to adenosine injection,
• Any acute or chronic illness or clinically relevant findings (i.e. liver,kidney, cardiovascular diseases) in the selection visit examinations.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

ADIR, a Servier Group company

INDUSTRY

Sponsor Role: collaborator

Institut de Recherches Internationales Servier

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Denis Strugala, Dr

Role: PRINCIPAL_INVESTIGATOR

Nuvisan GmbH

Locations

Nuvisan GmbH

Neu-Ulm, , Germany

Countries

Germany

Study Documents

Document Type: Individual Participant Data Set

View Document

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Document Type: Clinical Study Report

View Document

Document Type: Study-level clinical trial data

View Document

Other Identifiers

2017-000045-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CL1-RTCMP-001

Identifier Type: -

Identifier Source: org_study_id