Cardiovascular Effects of Selective I(f)-Channel Blockade

Phase 2

• Conditions: Postural Orthostatic Tachycardia Syndrome
• Interventions: Drug: beta-blocker (Metoprolol); Drug: I(f)-blocker (ivabradine); Drug: Placebo

• Registration Number: NCT00865917
• Lead Sponsor: Hannover Medical School

Brief Summary

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

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.

Study Timeline

• Study Start: 2008-11
• Status Verified: 2009-03
• Study First Submitted: 2009-03-18
• Study First Submitted QC: 2009-03-18
• Last Update Submitted: 2009-03-18
• Study First Posted: 2009-03-19
• Last Update Posted: 2009-03-19
• Primary Completion: 2010-11
• Study Completion: 2010-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Male
• Target Recruitment: 40

Inclusion Criteria

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
1	beta-blocker (Metoprolol)	beta-blocker
2	I(f)-blocker (ivabradine)	I(f)-blocker
3	Placebo	Placebo

Primary Outcome Measures

Name	Time	Method
Sub-study 'Orthostatic tolerance': Change in heart rate after 20 mins of passive orthostasis. Sub-study 'Sympathetic system': arterial pressure related heart rate	12-18 hours

Secondary Outcome Measures

Name	Time	Method
'Orthostatic tolerance': Hemodynamics during head-up tilt. Time to presyncope.	12-18 hours
'Sympathetic system': Muscle sympathetic nerve activity (MSNA).	12-18 hours

Trial Locations

Locations (2)

Franz-Volhard Centrum für Klinische Forschung; 🇩🇪 Berlin, Germany

Medizinische Hochschule Hannover; 🇩🇪 Hannover, Germany