Clinical trial NCT04744636: Vascular Function and Biomarker Assessments in Healthy Volunteers and in Patients With Type 2 Diabetes Mellitus
Official title: Target Involvement and Exploratory Biomarkers Investigations in Healthy Volunteers and in Patients With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes Mellitus
Keywords: Type 2 diabetes mellitus
Phase 1
Healthy volunteers
Clinical translational exploratory study
Target involvement
Exploratory biomarkers
Cardiovascular disease
Vascular function
Coronary flow reserve
Biopterins
Cutaneous blood flow
Lead sponsor: Servier
Sponsor class: INDUSTRY
Collaborators: name: ADIR, a Servier Group company
First posted: 2021-02-09
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

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)

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.

Primary outcomes:
measure: Guanylate triphosphate cyclohydrolase (GTP-CH) investigations
timeFrame: Day 1
measure: Guanylate triphosphate cyclohydrolase (GTP-CH) investigations
timeFrame: Day 1
measure: Guanylate triphosphate cyclohydrolase (GTP-CH) investigations
timeFrame: Day 2
measure: Guanylate triphosphate cyclohydrolase (GTP-CH) investigations
timeFrame: Day 1
Secondary outcomes:
measure: Adverse events
timeFrame: Through study completion, 3.5 weeks
measure: Blood pressure supine
timeFrame: Day 1
Other outcomes:
Locations:
city: Neu-Ulm
country: Germany
facility: Nuvisan GmbH
Study officials:
affiliation: Nuvisan GmbH
name: Denis Strugala, Dr
role: PRINCIPAL_INVESTIGATOR
References: