Clinical trial NCT00865917: Cardiovascular Effects of Selective I(f)-Channel Blockade
Official title: Einfluss Selektiver I(f)-Blockade Auf Orthostase-Toleranz Und Sympathikusaktivität Bei Gesunden
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Postural Orthostatic Tachycardia Syndrome
Keywords: POTS
Lead sponsor: Hannover Medical School
Sponsor class: OTHER
Collaborators: name: Charite University, Berlin, Germany
First posted: 2009-03-19
Enrollment: 40
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Sub-study 'Orthostatic tolerance': Change in heart rate after 20 mins of passive orthostasis. Sub-study 'Sympathetic system': arterial pressure related heart rate
timeFrame: 12-18 hours
Secondary outcomes:
measure: 'Orthostatic tolerance': Hemodynamics during head-up tilt. Time to presyncope.
timeFrame: 12-18 hours
measure: 'Sympathetic system': Muscle sympathetic nerve activity (MSNA).
timeFrame: 12-18 hours
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Franz-Volhard Centrum für Klinische Forschung
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
Study officials:
affiliation: Hannover Medical School
name: Jens Jordan, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.