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CompletedNCT03727542Updated Dec 11, 2018

Influence of Short AV Delay Permanent Pacing on Matrix Metalloproteinase Levels

An interventional study of adjustment of atrioventricular delay in DDD packers in Aortic Aneurysm, Aortic Diseases and Pacemaker DDD, sponsored by Istanbul University. Completed at 1 site in Turkey. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-12-11.

Sponsored by Istanbul University · Not applicable, Interventional, and Diagnostic

From the registry’s dates

  • Primary completion was Nov 2018, 7 years 10 months ago, and no results have been posted to the registry.
Phase
Not applicable
Study type
Interventional
Enrollment
20
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

As potential biomarkers of pressure-related aortic damage, matrix metalloproteinases (MMP) have been implicated in the pathogenesis of aortic aneurysm because of the important role they play in connective tissue homeostasis. In particular, a significant reduction in initially elevated serum MMP - 9 concentrations, compared with healthy controls, demonstrated after the aortic repair in patients with abdominal aortic aneurysm implies MMPs pivotal role in aortic aneurysms. Besides, due to an active degradation and repair processes taking place in the vascular wall governed by the balance between MMP enzymes and their inhibitors, MMP - 9, expression of which is predominantly associated with disruption of aortic elastic fibers, can also be detected in the serum of healthy subjects. Indeed, mechanical stress-induced upregulation of genes and their products stimulate MMP expression in the vascular wall, which is responsible for extracellular matrix degradation. Herein, it was hypothesized that reducing the acceleration rate of aortic pressure (aortic peak dP/dt) may decrease the mechanical stretch on the aortic wall which, may in turn, reduce the expression and serum levels of MMP-9.

Read the detailed description

The maximum value of acceleration rate of aortic pressure rise can be named as aortic peak dP/dt. It, likewise, corresponds to the maximum value of first derivative of aortic pressure curve with respect to time.Notably, aortic peak dP/dt would be one of the principal determinants of mechanical stress applied to the aortic wall. Hence, interventions aiming to reduce aortic peak dP/dt levels may open a new therapeutic avenue in the management of pressure-related vascular damages such as aortic aneurisms.

Since it is the principle determining factor of aortic peak dP/dt, changing LV contractility, thereby LV peak dP/dt, may be expected to lead to change aortic peak dP/dt values in the same direction. Therefore, reduction of LV dP/dt can lead to a reduction in aortic dP/dt. Previous finding strongly suggest that widening of the QRS complex could decrease LV contractility and correspondingly LV peak dP/dt value which may eventually lead to a reduction in aortic peak dP/dt.

From biomechanical point of view, as potential biomarkers of pressure-related aortic damage, matrix metalloproteinases (MMP) have been implicated in the pathogenesis of aortic aneurysm because of the important role they play in connective tissue homeostasis. In particular, a significant reduction in initially elevated serum MMP - 9 concentrations, compared with healthy controls, demonstrated after the aortic repair in patients with abdominal aortic aneurysm implies MMPs pivotal role in aortic aneurysms. Besides, due to an active degradation and repair processes taking place in the vascular wall governed by the balance between MMP enzymes and their inhibitors, MMP - 9, expression of which is predominantly associated with disruption of aortic elastic fibers, can also be detected in the serum of healthy subjects. Indeed, mechanical stress-induced upregulation of genes and their products stimulate MMP expression in the vascular wall, which is responsible for extracellular matrix degradation. Herein, we hypothesized that reducing the acceleration rate of aortic pressure (aortic peak dP/dt) may decrease the mechanical stretch on the aortic wall which, may in turn, reduce the expression and serum levels of MMP-9.

To this end, in the current trial, effect of the prolongation of QRS duration over a certain period of time by short AVD permanent pacing on the circulating levels of a vascular extracellular matrix degradation marker, MMP-9, was examined.

02

Conditions studied

  • Aortic Aneurysm
  • Aortic Diseases
  • Pacemaker DDD
03

In context

Aortic Aneurysm

663 studies on the registry are indexed under Aortic Aneurysm; 117 are open to participants now.

This study's enrollment of 20 is below the median of 62 across 318 interventional studies indexed under Aortic Aneurysm.

Browse Aortic Aneurysm studies →

Lead sponsor

Istanbul University is the lead sponsor of 496 studies on the registry; 79 are open to participants now.

Of its 5 completed or terminated interventional studies of FDA-regulated products, 1 (20%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  • Normal LV systolic function (EF>50%),
  • Healthy conduction systems
  • Noncritical coronary stenoses or normal coronary arteries
  • Ventricular pacing rate \<10% in the last 6 months detected at the interrogation of the pacemakers

Exclusion criteria

Exclusion Criteria:

  • Intra-ventricular conduction abnormalities (baseline QRS >100 msec.),
  • Mild to moderate aortic or mitral valve disease
  • Presence of atrial fibrillation
  • LV systolic dysfunction
05

Study design

Phase
Not applicable
Primary purpose
Diagnostic
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
20 participants (actual)

Study arms

  • Experimental
    Short AV-delay pacing

    Participants will be their own control. Serum samples will be collected at baseline while the participants were in sinus rhythm and after 3 weeks of short AV-delay pacing serum samples will be recollected to measure matrix metalloproteinase levels .

    Device: adjustment of atrioventricular delay in DDD packers

Interventions

  • Deviceadjustment of atrioventricular delay in DDD packers

    Atrioventricular delays are going to be adjusted as 60 milisecond shorter than the patients' native PR intervals in patients with already implanted permanent pacemakers.

06

What researchers measure

Primary outcomes

  1. Change in MMP - 9 serum concentration from baseline to at the end of 3 weeks follow-up

    MMP-9 serum concentration will be measured before and after short AV delay (wide QRS) pacing. Change in MMP-9 levels will be measured.

    Time frame: 3 weeks

07

Study locations

1 site
  • Istanbul University, Istanbul Faculty of Medicine, Department of Cardiology
    Istanbul, 34290, Turkey
08

References and documents

Individual participant data

Plan to share: Undecided

No publications or documents are linked to this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 11, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT03727542
Lead sponsor
Istanbul University
Responsible party
Dr. Murat Sezer (Clinical Professor, Istanbul University) — Principal investigator
First posted
Nov 1, 2018
Start date
Oct 15, 2018
Primary completion
Nov 15, 2018
Completion
Nov 15, 2018
Last update
Dec 11, 2018

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
Yes
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Dec 2018. You cannot join it, but the record below documents what was studied.

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