Cardiovascular Effects of Selective I(f)-Channel Blockade

Postural Orthostatic Tachycardia Syndrome Clinical Trial

Official title:

Einfluss Selektiver I(f)-Blockade Auf Orthostase-Toleranz Und Sympathikusaktivität Bei Gesunden

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00865917
• Other study ID #: CCB-CRC-07-02
• Status: Recruiting
• Phase: Phase 2
• First received: March 18, 2009
• Last updated: March 18, 2009
• Start date: November 2008
• Est. completion date: December 2010

Study information

• Verified date: March 2009
• Source: Hannover Medical School
• Contact: Heidrun Mehling, MD
• Phone: +49(0)30
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 2010
• Est. primary completion date: November 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 40 Years

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Postural Orthostatic Tachycardia Syndrome
• Tachycardia

Intervention

Drug:
• beta-blocker (Metoprolol)
Metoprolol 95 mg once per day
• I(f)-blocker (ivabradine)
ivabradine 7.5 mg once per day
• Placebo
matching appearance

Locations

Country	Name	City	State
Germany	Franz-Volhard Centrum für Klinische Forschung	Berlin
Germany	Medizinische Hochschule Hannover	Hannover

Sponsors (2)

Lead Sponsor	Collaborator
Hannover Medical School	Charite University, Berlin, Germany

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	'Orthostatic tolerance': Hemodynamics during head-up tilt. Time to presyncope.		12-18 hours	No
Secondary	'Sympathetic system': Muscle sympathetic nerve activity (MSNA).		12-18 hours	No