Intra-individual Variability and Circadian Rhythm of VEGF Levels and Interaction With Biomarkers

Intra-individual Variability and Circadian Rhythm of Systemic Vascular Endothelial Growth Factor (VEGF) Levels and Interaction With Biomarkers of Inflammation in Subjects With Normal Glucose Tolerance (NGT) and Patients With Type 2 Diabetes Without Diabetic Macular Edema (DME)

The study evaluates the intra-individual variability of VEGF levels over a period of 6 months as well as the circadian variation of VEGF levels, both under standardized conditions in patients with type 2 diabetes without DME and matched subjects with normal glucose tolerance (NGT). Secondary objectives of the study are to evaluate the relationship of individual VEGF-levels to biomarkers of inflammation, HbA1c and major cardiovascular risk factors.

Study Overview

• Status: Completed
• Conditions: Diabetic Macular Edema
• Intervention / Treatment: Other: Frequent blood and urine sampling and blood pressure measurement

• Study Type: Observational
• Enrollment (Actual): 40

Contacts and Locations

Study Locations

• Germany
  • Dresden, Germany, 01307
    • GWT-TUD GmbH / Studienzentrum Hanefeld

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Community sample of healthy volunteers, type 2 diabetes patients of the study center

Description

Inclusion Criteria:

• Written informed consent
• Age equal to or between 50 and 80 years
• Subjects with normal glucose tolerance confirmed by glucose tolerance test (control group) or patients with type 2 diabetes: diabetes duration 5-25 years; HbA1c equal to or between 6.5 and 9% (diabetes group)
• Ability to understand and follow study-related instructions

Exclusion Criteria:

• DME
• hsCRP > 10 mg/dl
• Acute infections
• Acute or chronic inflammatory diseases
• Immune diseases
• Treatment with immune suppressive drugs
• Treatment with glucocorticoids
• Myocardial infarction and stroke within 1 year before inclusion
• Hemorrhage within the previous 5 years
• Surgeries within the previous 3 months
• Oncological diseases
• Women who are pregnant or breast-feeding

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Control group; Subjects with normal glucose tolerance	Other: Frequent blood and urine sampling and blood pressure measurement; Blood and urine sampling for the determination of VEGF and biomarkers
Diabetes group; Patients with type 2 diabetes	Other: Frequent blood and urine sampling and blood pressure measurement; Blood and urine sampling for the determination of VEGF and biomarkers

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VEGF-A	Plasma levels determined in the morning under fasted conditions	Baseline, month 1, 2, 3, 4, 5 and 6
VEGF-B	Plasma levels determined in the morning under fasted conditions	Baseline, month 1, 2, 3, 4, 5 and 6
VEGF-C	Plasma levels determined in the morning under fasted conditions	Baseline, month 1, 2, 3, 4, 5 and 6
Placental growth factor	Plasma levels determined in the morning under fasted conditions	Baseline, month 1, 2, 3, 4, 5 and 6
VEGF-A	Plasma levels determined over the day	Hourly over 12 hours
VEGF-B	Plasma levels determined over the day	Hourly over 12 hours
VEGF-C	Plasma levels determined over the day	Hourly over 12 hours
Placental growth factor	Plasma levels determined over the day	Hourly over 12 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycated hemoglobin (HbA1c)	Plasma levels determined in the morning under fasted conditions	Baseline, month 1, 2, 3, 4, 5 and 6
High-sensitivity C-reactive protein (hCRP)	Serum levels determined in the morning under fasted conditions	Baseline, month 1, 2, 3, 4, 5 and 6
Matrix metallopeptidase 9 (MMP-9)	Plasma levels determined in the morning under fasted conditions	Baseline, month 1, 2, 3, 4, 5 and 6
MMP-9	Plasma levels determined over the day	Hourly over 12 hours
Adiponectin	Serum levels determined in the morning under fasted condition	Baseline, month 1, 2, 3, 4, 5 and 6
Adiponectin	Serum levels determined over the day	Hourly over 12 hours
Cystatin C	Serum levels determined in the morning under fasted condition	Baseline, month 1, 2, 3, 4, 5 and 6
Cystatin C	Serum levels determined over the day	Hourly over 12 hours
Albumin	Urine levels determined in the morning under fasted condition	Baseline, month 1, 2, 3, 4, 5 and 6
Creatinine	Urine levels determined in the morning under fasted condition	Baseline, month 1, 2, 3, 4, 5 and 6
Creatinine	Serum levels determined in the morning under fasted condition	Baseline, month 1, 2, 3, 4, 5 and 6
Blood pressure		Baseline, month 1, 2, 3, 4, 5 and 6, once over 24 hours

Collaborators and Investigators

• Sponsor: GWT-TUD GmbH
• Collaborators: Novartis
• Investigators: Principal Investigator: Markolf Hanefeld, Prof. Dr., Study center Prof. Hanefeld, GWT-TUD GmbH

Publications and helpful links

General Publications

• Hanefeld M, Engelmann K, Appelt D, Sandner D, Weigmann I, Ganz X, Pistrosch F, Kohler C, Gasparic A, Birkenfeld AL. Intra-individual variability and circadian rhythm of vascular endothelial growth factors in subjects with normal glucose tolerance and type 2 diabetes. PLoS One. 2017 Oct 9;12(10):e0184234. doi: 10.1371/journal.pone.0184234. eCollection 2017.

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: December 19, 2014
• First Submitted That Met QC Criteria: December 19, 2014
• First Posted (Estimate): December 24, 2014

Study Record Updates

• Last Update Posted (Actual): September 6, 2017
• Last Update Submitted That Met QC Criteria: September 4, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Macular Edema
• Other Study ID Numbers: VEGF Bio

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No