Cardiovascular Effects of Selective I(f)-Channel Blockade

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2009 by Hannover Medical School.
Recruitment status was  Recruiting
Charite University, Berlin, Germany
Information provided by:
Hannover Medical School Identifier:
First received: March 18, 2009
Last updated: NA
Last verified: March 2009
History: No changes posted
The study compares three treatment modalities in a human model of Postural orthostatic tachycardia syndrome (POTS): beta-blockers, I(f)-blockers, and placebo.

Condition Intervention Phase
Postural Orthostatic Tachycardia Syndrome
Drug: beta-blocker (Metoprolol)
Drug: I(f)-blocker (ivabradine)
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Einfluss Selektiver I(f)-Blockade Auf Orthostase-Toleranz Und Sympathikusaktivität Bei Gesunden

Resource links provided by NLM:

Further study details as provided by Hannover Medical School:

Primary Outcome Measures:
  • Sub-study 'Orthostatic tolerance': Change in heart rate after 20 mins of passive orthostasis. Sub-study 'Sympathetic system': arterial pressure related heart rate [ Time Frame: 12-18 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 'Orthostatic tolerance': Hemodynamics during head-up tilt. Time to presyncope. [ Time Frame: 12-18 hours ] [ Designated as safety issue: No ]
  • 'Sympathetic system': Muscle sympathetic nerve activity (MSNA). [ Time Frame: 12-18 hours ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: November 2008
Estimated Study Completion Date: December 2010
Estimated Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Drug: beta-blocker (Metoprolol)
Metoprolol 95 mg once per day
Experimental: 2
Drug: I(f)-blocker (ivabradine)
ivabradine 7.5 mg once per day
Placebo Comparator: 3
Drug: Placebo
matching appearance

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.


Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00865917

Contact: Heidrun Mehling, MD +49(0)30 ext 94171296
Contact: Jens Tank, MD +49(0)511 ext 532 2723

Franz-Volhard Centrum für Klinische Forschung Recruiting
Berlin, Germany, 13125
Contact: Heidrun Mehling, MD    +49(0)30 ext 94171296      
Medizinische Hochschule Hannover Recruiting
Hannover, Germany, 30625
Contact: Jens Tank, MD    +49(0)30 ext 5322723      
Contact: Karsten Heusser, MD    +49(0)30 ext 5322723      
Sponsors and Collaborators
Hannover Medical School
Charite University, Berlin, Germany
Study Director: Jens Jordan, MD Hannover Medical School
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Heidrum Mehling, Dr. med., Franz-Volhard-Centrum für Klinische Forschung Identifier: NCT00865917     History of Changes
Other Study ID Numbers: CCB-CRC-07-02 
Study First Received: March 18, 2009
Last Updated: March 18, 2009
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Hannover Medical School:

Additional relevant MeSH terms:
Autonomic Nervous System Diseases
Primary Dysautonomias
Postural Orthostatic Tachycardia Syndrome
Arrhythmias, Cardiac
Cardiovascular Diseases
Heart Diseases
Nervous System Diseases
Orthostatic Intolerance
Pathologic Processes
Adrenergic beta-Antagonists
Adrenergic Agents
Adrenergic Antagonists
Adrenergic beta-1 Receptor Antagonists
Anti-Arrhythmia Agents
Antihypertensive Agents
Autonomic Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Sympatholytics processed this record on May 26, 2016