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

Sponsor

Institut de Recherches Internationales Servier (Other)

Overall Status

Completed

CT.gov ID

NCT04744636

Collaborator

ADIR, a Servier Group company (Industry)

100

Enrollment

Location

Arms

17.4

Actual Duration (Months)

5.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: Other Drug: Other	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

100 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

Target Involvement and Exploratory Biomarkers Investigations in Healthy Volunteers and in Patients With Type 2 Diabetes Mellitus

Actual Study Start Date :

Apr 3, 2017

Actual Primary Completion Date :

Sep 15, 2018

Actual Study Completion Date :

Sep 15, 2018

Arms and Interventions

Arm	Intervention/Treatment
Other: Healthy volunteers aged of 18-30 years	Drug: 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.
Other: Healthy volunteers aged of 50-59 years	Drug: 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.
Other: Healthy volunteers aged of 60-70 years	Drug: 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.
Other: Type 2 diabetic patients aged of 50-70 years	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.

Outcome Measures

Primary Outcome Measures

Guanylate triphosphate cyclohydrolase (GTP-CH) investigations [Day 1]
Plasma/platelet levels of Dihydrobiopterin (BAH)/Tetrahydrobiopterin (BH4), Cyclic guanosine monophosphate (cGMP)
Guanylate triphosphate cyclohydrolase (GTP-CH) investigations [Day 1]
Blood flow changes for vascular endothelial function
Guanylate triphosphate cyclohydrolase (GTP-CH) investigations [Day 2]
Coronary flow reserve
Guanylate triphosphate cyclohydrolase (GTP-CH) investigations [Day 1]
Genomic market (blood) DNA and/or RNA characteristics of genes such as GTP Cyclohydrolase 1 (GCH)

Secondary Outcome Measures

Adverse events [Through study completion, 3.5 weeks]
Occurence of any adverse events
Blood pressure supine [Day 1]
Relevant abnormalities on supine blood pressure

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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)

Non inclusion Criteria:

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.