Cardiovascular Effects of Selective I(f)-Channel Blockade

Hannover Medical School (MHH)

Status and phase: Unknown; Phase 2

Conditions: Postural Orthostatic Tachycardia Syndrome

Treatments: Drug: Placebo; Drug: beta-blocker (Metoprolol); Drug: I(f)-blocker (ivabradine)

Study type: Interventional

Funder types: Other

Identifiers

NCT00865917

CCB-CRC-07-02

Details and patient eligibility

About

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

Full 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.

Enrollment: 40 estimated patients

Sex: Male

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

---

40 participants in 3 patient groups, including a placebo group

1

Active Comparator group

Description:

beta-blocker

Treatment:

Drug: beta-blocker (Metoprolol)

2

Experimental group

Description:

I(f)-blocker

Treatment:

Drug: I(f)-blocker (ivabradine)

3

Placebo Comparator group

Description:

Placebo

Treatment:

Drug: Placebo