Cardiovascular Effects of Selective I(f)-Channel Blockade

NCT ID: NCT00865917

Last Updated: 2009-03-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-11-30

Study Completion Date

2010-12-31

Brief Summary

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The study compares three treatment modalities in a human model of Postural orthostatic tachycardia syndrome (POTS): beta-blockers, I(f)-blockers, and placebo.

Detailed Description

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Elevated heart rate may lead to cardiac disease in the long-term. Therefore, drugs lowering heart rate are useful. Beta-blockers are an established treatment modality. They not only lower heart rate but also contractility, which might be undesirable in certain tachycardic disorders.

Postural orthostatic tachycardia syndrome (POTS) patients complain about dizziness, weakness, headache, lightheadedness, fatigue, nausea, and presyncope. In some patients there is elevated heart rate even during supine rest. In POTS patients it is preferable to lower heart rate without reducing cardiac contractility which can be achieved by using so-called I(f)-blockers. Thus, they might be superior to beta-blockers in POTS.

In our study, we artificially generate POTS in healthy male subjects for about 48 hours. We want to compare the cardiovascular effects and orthostatic tolerance of the following treatments: beta-blocker, I(f)-blocker, and placebo.

Moreover, we will quantify changes in cardiovascular autonomic regulation brought about by I(f)-blockade versus placebo.

Conditions

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Postural Orthostatic Tachycardia Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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1

beta-blocker

Group Type ACTIVE_COMPARATOR

beta-blocker (Metoprolol)

Intervention Type DRUG

Metoprolol 95 mg once per day

2

I(f)-blocker

Group Type EXPERIMENTAL

I(f)-blocker (ivabradine)

Intervention Type DRUG

ivabradine 7.5 mg once per day

3

Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

matching appearance

Interventions

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beta-blocker (Metoprolol)

Metoprolol 95 mg once per day

Intervention Type DRUG

I(f)-blocker (ivabradine)

ivabradine 7.5 mg once per day

Intervention Type DRUG

Placebo

matching appearance

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* healthy male
* age 18-40 years
* BMI: 18-30 kg/m²
* arterial blood pressure \<=160/100 mm Hg
* co-operativity
* voluntariness

Exclusion Criteria

* conditions in which treatment might be ineffective or insecure
* co-medication within the last 4 weeks
* participation in another clinical trial within the last 4 weeks
* unability to understand the study's aim
* drug or alcohol abuse
* secondary hypertension
* creatinine \> 130 μM (1.47 mg/dl)
* GOT/GPT \> 2 times normal
* GGT \> 3 times normal
* contraindications against reboxetine, beta-blocker, ivabradine
* asthma, psoriasis
* diabetes
* heart failure (NYHA III or IV)
* coronary artery disease
* peripheral occlusive disease
* cerebrovascular disease
* ventricular extrasystoles (Lown III-V)
* atrial fibrillation
* resting heart rate \<60/min
* neurologic/psychiatric disorder
* pulmonary hypertension
* dysthyroid metabolism
Minimum Eligible Age

18 Years

Maximum Eligible Age

40 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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Charite University, Berlin, Germany

OTHER

Sponsor Role collaborator

Hannover Medical School

OTHER

Sponsor Role lead

Responsible Party

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Franz-Volhard-Centrum für Klinische Forschung

Principal Investigators

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Jens Jordan, MD

Role: STUDY_DIRECTOR

Hannover Medical School

Locations

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Franz-Volhard Centrum für Klinische Forschung

Berlin, , Germany

Site Status RECRUITING

Medizinische Hochschule Hannover

Hanover, , Germany

Site Status RECRUITING

Countries

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Germany

Central Contacts

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Heidrun Mehling, MD

Role: CONTACT

+49(0)30 ext. 94171296

Jens Tank, MD

Role: CONTACT

+49(0)511 ext. 532 2723

Facility Contacts

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Heidrun Mehling, MD

Role: primary

+49(0)30 ext. 94171296

Jens Tank, MD

Role: primary

+49(0)30 ext. 5322723

Karsten Heusser, MD

Role: backup

+49(0)30 ext. 5322723

References

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Heusser K, Tank J, Brinkmann J, Schroeder C, May M, Grosshennig A, Wenzel D, Diedrich A, Sweep FC, Mehling H, Luft FC, Jordan J. Preserved Autonomic Cardiovascular Regulation With Cardiac Pacemaker Inhibition: A Crossover Trial Using High-Fidelity Cardiovascular Phenotyping. J Am Heart Assoc. 2016 Jan 13;5(1):e002674. doi: 10.1161/JAHA.115.002674.

Reference Type DERIVED
PMID: 26764413 (View on PubMed)

Zoerner AA, Schroeder C, Kayacelebi AA, Suchy MT, Gutzki FM, Stichtenoth DO, Tank J, Jordan J, Tsikas D. A validated, rapid UPLC-MS/MS method for simultaneous ivabradine, reboxetine, and metoprolol analysis in human plasma and its application to clinical trial samples. J Chromatogr B Analyt Technol Biomed Life Sci. 2013 May 15;927:105-11. doi: 10.1016/j.jchromb.2013.01.016. Epub 2013 Jan 29.

Reference Type DERIVED
PMID: 23434314 (View on PubMed)

Other Identifiers

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CCB-CRC-07-02

Identifier Type: -

Identifier Source: org_study_id

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