NCT02118753

Brief Summary

In the laboratory, the researchers will investigate whether the drug eplerenone improves contractile function after ischemia and reperfusion in heart tissue.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
24

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Mar 2014

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2014

Completed
13 days until next milestone

First Submitted

Initial submission to the registry

March 14, 2014

Completed
1 month until next milestone

First Posted

Study publicly available on registry

April 21, 2014

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2015

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2016

Completed
Last Updated

January 12, 2016

Status Verified

January 1, 2016

Enrollment Period

1.8 years

First QC Date

March 14, 2014

Last Update Submit

January 11, 2016

Conditions

Ischemia-reperfusion Injury

Keywords

ischemia-reperfusion injury

Outcome Measures

Primary Outcomes (1)

  • contractile function after simulated ischemia and reperfusion in response to eplerenone

    The recovery of contractile function (% of baseline) in human myocardial tissue after simulated ischemia and reperfusion in 2 trabeculae will be compared: 1 of the trabeculae will be exposed to eplerenone, the other to vehicle. We will use the experimental set up as described by Speechly-Dick et al. with small modifications to allow simultaneous measurement of 2 trabeculae from 1 patient. The two trabeculae will be dissected and vertically suspended in an organ bath and linked to a force transducer. During electrical field stimulation, we will calculate the developed force (difference between maximal tension during contraction and minimal tension during relaxation), maximal speed of tension development during contraction and maximal speed of tension during relaxation. We will average these parameters for baseline, and during the experiment. Functional recovery will be expressed as a percentage of baseline.

    210 minutes

Study Arms (2)

ischemic preconditioning

NO INTERVENTION

After baseline recordings of contractile function, the investigators will assign 2 trabeculae of each patient to either a stimulus for (1) ischemic preconditioning (IP) or (2) no IP. Subsequently, the trabeculae will be exposed to 90 min of ischemia, followed by 120 minutes of recovery. The investigators will measure the recovery of contractile function in both trabeculae. This experiment serves as a positive control, to ensure that our model is still working properly.

eplerenone

EXPERIMENTAL

In the next patients, a similar ischemia-reperfusion experiment will be performed, but now the 2 trabeculae will be randomized to pretreatment with eplerenone or DMSO. The percentage recovery (compared to baseline) of contractile force of the trabeculae at the end of reperfusion will serve as the primary endpoint.

Drug: Eplerenone

Interventions

EplerenoneDRUG

eplerenone administered ex vivo (to the organ bath in which human atrial tissue is exposed)

Also known as: Inspra
eplerenone

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • age\>18 years
  • willing to sign informed consent
  • planned elective surgery with extracorporal circulation

You may not qualify if:

  • use of theophylline
  • use of sulfonylureas
  • use of oral antiarrhythmics (not beta blockers)
  • use of dipyridamole, use of mineralocorticoid receptor antagonists
  • atrial arrhythmias
  • right ventricular failure
  • known atrial enlargement

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Radboud University Medical Centre

Nijmegen, Gelderland, 6500HB, Netherlands

Location

Related Publications (2)

  • Riksen NP, Zhou Z, Oyen WJ, Jaspers R, Ramakers BP, Brouwer RM, Boerman OC, Steinmetz N, Smits P, Rongen GA. Caffeine prevents protection in two human models of ischemic preconditioning. J Am Coll Cardiol. 2006 Aug 15;48(4):700-7. doi: 10.1016/j.jacc.2006.04.083. Epub 2006 Jul 24.

    PMID: 16904537BACKGROUND

  • Speechly-Dick ME, Grover GJ, Yellon DM. Does ischemic preconditioning in the human involve protein kinase C and the ATP-dependent K+ channel? Studies of contractile function after simulated ischemia in an atrial in vitro model. Circ Res. 1995 Nov;77(5):1030-5. doi: 10.1161/01.res.77.5.1030.

    PMID: 7554138BACKGROUND

MeSH Terms

Conditions

Reperfusion Injury

Interventions

Eplerenone

Condition Hierarchy (Ancestors)

Vascular DiseasesCardiovascular DiseasesPostoperative ComplicationsPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

LactonesOrganic ChemicalsPregnenesPregnanesSteroidsFused-Ring CompoundsPolycyclic Compounds

Study Officials

  • Niels P. Riksen, Dr

    Radboud University Medical Center

    PRINCIPAL INVESTIGATOR

  • Henri A. van Swieten, Prof dr ir

    Radboud University Medical Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 14, 2014

First Posted

April 21, 2014

Study Start

March 1, 2014

Primary Completion

December 1, 2015

Study Completion

January 1, 2016

Last Updated

January 12, 2016

Record last verified: 2016-01

Locations

NL(1)