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

Type 2 Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04744636
• Other study ID #: CL1-RTCMP-001
• Secondary ID: 2017-000045-42
• Status: Completed
• Phase: Phase 1
• Start date: April 3, 2017
• Est. completion date: September 15, 2018

Study information

• Verified date: November 2021
• Source: Servier
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: September 15, 2018
• Est. primary completion date: September 15, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

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 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.

Locations

Country	Name	City	State
Germany	Nuvisan GmbH	Neu-Ulm

Sponsors (2)

Lead Sponsor	Collaborator
Institut de Recherches Internationales Servier	ADIR, a Servier Group company

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Guanylate triphosphate cyclohydrolase (GTP-CH) investigations	Plasma/platelet levels of Dihydrobiopterin (BAH)/Tetrahydrobiopterin (BH4), Cyclic guanosine monophosphate (cGMP)	Day 1
Primary	Guanylate triphosphate cyclohydrolase (GTP-CH) investigations	Blood flow changes for vascular endothelial function	Day 1
Primary	Guanylate triphosphate cyclohydrolase (GTP-CH) investigations	Coronary flow reserve	Day 2
Primary	Guanylate triphosphate cyclohydrolase (GTP-CH) investigations	Genomic market (blood) DNA and/or RNA characteristics of genes such as GTP Cyclohydrolase 1 (GCH)	Day 1
Secondary	Adverse events	Occurence of any adverse events	Through study completion, 3.5 weeks
Secondary	Blood pressure supine	Relevant abnormalities on supine blood pressure	Day 1

External Links

•   Results summary
•   Scientific publication