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

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ClinicalTrials.gov Identifier: NCT04744636
Recruitment Status : Completed
First Posted : February 9, 2021
Last Update Posted : April 23, 2021
Sponsor:
Collaborator:
ADIR, a Servier Group company
Information provided by (Responsible Party):
Servier ( Institut de Recherches Internationales Servier )

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 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.

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Study Type : Interventional  (Clinical Trial)
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 : April 3, 2017
Actual Primary Completion Date : September 15, 2018
Actual Study Completion Date : September 15, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.

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.

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.

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.




Primary Outcome Measures :
  1. Guanylate triphosphate cyclohydrolase (GTP-CH) investigations [ Time Frame: Day 1 ]
    Plasma/platelet levels of Dihydrobiopterin (BAH)/Tetrahydrobiopterin (BH4), Cyclic guanosine monophosphate (cGMP)

  2. Guanylate triphosphate cyclohydrolase (GTP-CH) investigations [ Time Frame: Day 1 ]
    Blood flow changes for vascular endothelial function

  3. Guanylate triphosphate cyclohydrolase (GTP-CH) investigations [ Time Frame: Day 2 ]
    Coronary flow reserve

  4. Guanylate triphosphate cyclohydrolase (GTP-CH) investigations [ Time Frame: Day 1 ]
    Genomic market (blood) DNA and/or RNA characteristics of genes such as GTP Cyclohydrolase 1 (GCH)


Secondary Outcome Measures :
  1. Adverse events [ Time Frame: Through study completion, 3.5 weeks ]
    Occurence of any adverse events

  2. Blood pressure supine [ Time Frame: Day 1 ]
    Relevant abnormalities on supine blood pressure



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04744636


Locations
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Germany
Nuvisan GmbH
Neu-Ulm, Germany, 89231
Sponsors and Collaborators
Institut de Recherches Internationales Servier
ADIR, a Servier Group company
Investigators
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Principal Investigator: Denis Strugala, Dr Nuvisan GmbH
Additional Information:
Study Data/Documents: Individual Participant Data Set  This link exits the ClinicalTrials.gov site

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Responsible Party: Institut de Recherches Internationales Servier
ClinicalTrials.gov Identifier: NCT04744636    
Other Study ID Numbers: CL1-RTCMP-001
2017-000045-42 ( EudraCT Number )
First Posted: February 9, 2021    Key Record Dates
Last Update Posted: April 23, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data.

Access can be requested for all interventional clinical studies:

  • used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
  • where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.

In addition, access can be requested for all interventional clinical studies in patients:

  • sponsored by Servier
  • with a first patient enrolled as of 1 January 2004 onwards
  • for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: After Marketing Authorisation in EEA or US if the study is used for the approval.
Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
URL: https://clinicaltrials.servier.com/

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Servier ( Institut de Recherches Internationales Servier ):
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
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases