- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03178019
DPP4 Activity, Microvascular Reactivity and Inflammation (DPP4)
Dipeptidyl Peptidase 4 (DPP4) Activity and Its Associations With Endothelial Dysfunction, Inflammatory and Metabolic Markers, Heart Rate and Blood Pressure Variability, and Measures of Adiposity in Subjects With Different Grades of Glucose Tolerance
Study Overview
Status
Intervention / Treatment
Detailed Description
Dipeptidyl peptidase 4 (DPP4), also known as adenosine deaminase binding protein or cluster of differentiation 26 (CD26), is a serine exopeptidase able to inactivate various oligopeptides composed of proline, hydroxyproline, or alanine as the penultimate residue. In recent years, DPP4 has received attention due to its ability to rapidly inactivate the main incretins secreted by the gastrointestinal tract: glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). As its own name already says, incretins enhance insulin secretion in a glucose-dependent fashion, but also suppress or modulate glucagon secretion. Since it was demonstrated that type 2 diabetes mellitus (T2D) have incretin deficiency and hyperglucagonemia on its physiopathology, gliptins emerged as a new class of drugs for the treatment of this disease, acting through the inhibition of DPP4 and consequently ameliorating these defects.
DPP4 not only inactivate incretins but also a number of cytokines, chemokines, and neuropeptides involved in inflammation, immunity and vascular function. Furthermore, evidence from in vitro and in vivo studies, including clinical ones in T2D, suggested that gliptins' inhibition of DPP4 was associated with reduction of inflammatory biomarkers and also attenuation of endothelial dysfunction and atherogenesis, possibly through regulation of the DPP4 substrates.
There is a paucity of studies that associate the constitutive levels of DPP4 activity (i.e., outside the context of pharmacological inhibition of the enzyme) with markers of inflammation and endothelial function, specially tested on skin microcirculation. We hypothesized that constitutive levels of DPP4 activity might be directly associated to inflammation and inversely correlated with skin blood flux and one or more components of vasomotion (suggesting an association with endothelial disfunction) even in the absence of diabetes. Our aim was to investigate the associations between constitutive levels of DPP4 activity and inflammatory biomarkers, skin microvascular reactivity, gut peptides, insulin resistance indexes, heart rate and blood pressure variability, and measures of adiposity in subjects with different grades of glucose tolerance.
Study Type
Enrollment (Actual)
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- BMI ≥ 25.0 kg/m²
- Any degree of glucose tolerance
Exclusion Criteria:
- BMI < 25.0 kg/m²
- Uncontrolled chronic diseases, such as arterial hypertension
- Smoking
- Severe alcoholism
- Moderate to severe chronic kidney disease, heart failure, chronic lung disease, and chronic liver disease
- Fasting serum triglycerides > 400 mg/dl
- Fasting serum cholesterol > 300 mg/dl
- Pregnancy and breastfeeding
- Women in the climacteric period
- Individuals who undergo bariatric surgery
- Acute disease at the time of sampling
- Initiation of statin or change in its dose within 60 days
- Use of aspirin and/or fluconazole within 10 days prior to the exams
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Euglycemia group
Normoglycemic/normotolerant subjects
|
This was a cross-sectional study in which participants were subjected to a screening phase before being eligible to participate in the study.
All subjects were submitted to Laser-Doppler methods (assessment of microcirculatory blood flow), bioimpedance analysis (assessment of body composition), venous blood collections (laboratory analysis), and Finometer Pro (assessment of heart rate variability and blood pressure variability).
Other Names:
|
Prediabetes group
Subjects with prediabetes
|
This was a cross-sectional study in which participants were subjected to a screening phase before being eligible to participate in the study.
All subjects were submitted to Laser-Doppler methods (assessment of microcirculatory blood flow), bioimpedance analysis (assessment of body composition), venous blood collections (laboratory analysis), and Finometer Pro (assessment of heart rate variability and blood pressure variability).
Other Names:
|
Diabetes group
Subjects with type 2 diabetes mellitus
|
This was a cross-sectional study in which participants were subjected to a screening phase before being eligible to participate in the study.
All subjects were submitted to Laser-Doppler methods (assessment of microcirculatory blood flow), bioimpedance analysis (assessment of body composition), venous blood collections (laboratory analysis), and Finometer Pro (assessment of heart rate variability and blood pressure variability).
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Intergroup analysis of the associations between DPP4 activity and skin microvascular reactivity
Time Frame: 63 minutes
|
Intergroup analysis of the associations between DPP4 activity and skin microvascular reactivity (blood flux and vasomotion evaluated by Laser-Doppler methods) - baseline assessment and at 30 and 60 min after a standardized meal intake (ingested over 3 minutes)
|
63 minutes
|
Intergroup analysis of the associations between DPP4 activity and markers of inflammation
Time Frame: 63 minutes
|
Intergroup analysis of the associations between DPP4 activity and markers of inflammation - baseline assessment and at 30 and 60 min after a standardized meal intake (ingested over 3 minutes)
|
63 minutes
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Intergroup analysis of the associations between DPP4 activity and biochemical parameters
Time Frame: 63 minutes
|
Intergroup comparisons between the associations of DPP4 activity and Biochemical parameters (including gut peptides) - baseline assessment and at 30 and 60 min after a standardized meal intake (ingested over 3 minutes)
|
63 minutes
|
Intergroup analysis of the associations between DPP4 activity and insulin resistance indexes, heart rate and blood pressure variability, and measures of adiposity
Time Frame: Baseline evaluation
|
Intergroup analysis of the associations between DPP4 activity and insulin resistance indexes, heart rate and blood pressure variability (evaluated by Finometer Pro), and measures of adiposity at baseline
|
Baseline evaluation
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Wellington S Silva Júnior, MD, State University of Rio de Janeiro
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 940.029
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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