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
Sponsor:
Collaborator:
Charite University, Berlin, Germany
Information provided by:
Hannover Medical School
ClinicalTrials.gov Identifier:
NCT00865917
First received: March 18, 2009
Last updated: NA
Last verified: March 2009
History: No changes posted
  Purpose

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
beta-blocker
Drug: beta-blocker (Metoprolol)
Metoprolol 95 mg once per day
Experimental: 2
I(f)-blocker
Drug: I(f)-blocker (ivabradine)
ivabradine 7.5 mg once per day
Placebo Comparator: 3
Placebo
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.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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
  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 ClinicalTrials.gov identifier: NCT00865917

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

Locations
Germany
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
Investigators
Study Director: Jens Jordan, MD Hannover Medical School
  More Information

No publications provided by Hannover Medical School

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Heidrum Mehling, Dr. med., Franz-Volhard-Centrum für Klinische Forschung
ClinicalTrials.gov 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:
POTS

Additional relevant MeSH terms:
Tachycardia
Postural Orthostatic Tachycardia Syndrome
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Orthostatic Intolerance
Primary Dysautonomias
Autonomic Nervous System Diseases
Nervous System Diseases
Metoprolol
Adrenergic beta-Antagonists
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic beta-1 Receptor Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014