Postural Orthostatic Tachycardia SyndromePhase 2NCT00865917
Cardiovascular Effects of Selective I(f)-Channel Blockade
A Phase 2 study testing beta-blocker (Metoprolol) and I(f)-blocker (ivabradine) in people with Postural Orthostatic Tachycardia Syndrome, run by Hannover Medical School at 2 sites in Germany.
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. Read more about this study
- Who is it for?
- Ages 18 to 40 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Postural Orthostatic Tachycardia Syndrome
- What is being tested?
- beta-blocker (Metoprolol) and I(f)-blocker (ivabradine)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 2 sitesGermany
- Study dates
- Nov 2008to Dec 2010
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- healthy male
- age 18-40 years
- BMI: 18-30 kg/m²
- arterial blood pressure <=160/100 mm Hg
- co-operativity
- voluntariness
Who cannot join
- 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
Show all 22Show fewer
- 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 locations and contacts
2 sites in 1 country.
Heidrun Mehling, MD contact
Jens Tank, MD contact
Germany2 sites, 2 recruiting
- Recruiting
Franz-Volhard Centrum für Klinische Forschung
Berlin, 13125
Heidrun Mehling, MD, +49(0)30 ext. 94171296
- Recruiting
Medizinische Hochschule Hannover
Hanover, 30625
Jens Tank, MD, +49(0)30 ext. 5322723
Karsten Heusser, MD, +49(0)30 ext. 5322723
About this study
Official title: Einfluss Selektiver I(f)-Blockade Auf Orthostase-Toleranz Und Sympathikusaktivität Bei Gesunden
The study compares three treatment modalities in a human model of Postural orthostatic tachycardia syndrome (POTS): beta-blockers, I(f)-blockers, and placebo.
Read the 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.
- Being tested
- beta-blocker (Metoprolol), I(f)-blocker (ivabradine), Placebo
- Keywords
- POTS
- Medical subject headings
- Postural Orthostatic Tachycardia Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
beta-blocker (Metoprolol)Drug
Metoprolol 95 mg once per day
I(f)-blocker (ivabradine)Drug
ivabradine 7.5 mg once per day
PlaceboDrug
matching appearance
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | beta-blocker Receives: Drug: beta-blocker (Metoprolol) |
| 2 | Experimental | I(f)-blocker Receives: Drug: I(f)-blocker (ivabradine) |
| 3 | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sub-study 'Orthostatic tolerance': Change in heart rate after 20 mins of passive orthostasis. Sub-study 'Sympathetic system': arterial pressure related heart rate
Measured: 12-18 hours
Secondary outcomes (2)
'Orthostatic tolerance': Hemodynamics during head-up tilt. Time to presyncope.
Measured: 12-18 hours
'Sympathetic system': Muscle sympathetic nerve activity (MSNA).
Measured: 12-18 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2009 (estimated)
- Study startNov 2008
- Primary completionNov 2010 (estimated)
- Study completionDec 2010 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Postural Orthostatic Tachycardia SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hannover Medical School
- Sponsor type
- University, hospital or other
- Collaborators
- Charite University, Berlin, Germany
- Investigators
- Jens Jordan, MD, Study director, Hannover Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00865917
- Sponsor's protocol ID
- CCB-CRC-07-02
- Status last verified
- Mar 2009
- First submitted
- 18 Mar 2009
- Last updated
- 19 Mar 2009
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 26764413Zoerner 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.
PubMed 23434314
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Einfluss Selektiver I(f)-Blockade Auf Orthostase-Toleranz Und Sympathikusaktivität Bei Gesunden
- ClinicalTrials.gov ID
- NCT00865917
- Acronym / sponsor ID
- CCB-CRC-07-02
- Keywords
- POTS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Hannover Medical SchoolUniversity, hospital or other
- Collaborators
- Charite University, Berlin, Germany
- Study start
- Nov 2008
- Primary completion
- Nov 2010 (estimated)
- Study completion
- Dec 2010 (estimated)
- First posted
- 19 Mar 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: beta-blocker (Metoprolol)beta-blocker |
| 2 | Experimental | Drug: I(f)-blocker (ivabradine)I(f)-blocker |
| 3 | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- healthy male
- age 18-40 years
- BMI: 18-30 kg/m²
- arterial blood pressure <=160/100 mm Hg
- co-operativity
Key exclusion criteria (22 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| beta-blocker (Metoprolol)Metoprolol 95 mg once per day | Drug | 1 |
| I(f)-blocker (ivabradine)ivabradine 7.5 mg once per day | Drug | 2 |
| Placebomatching appearance | Drug | 3 |
Primary outcome
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
2 secondary outcomes
'Orthostatic tolerance': Hemodynamics during head-up tilt. Time to presyncope.
Time frame: 12-18 hours
'Sympathetic system': Muscle sympathetic nerve activity (MSNA).
Time frame: 12-18 hours
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2009.
- Derived from this study: PubMed 26764413Heusser 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.
- Derived from this study: PubMed 23434314Zoerner 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Heidrun Mehling, MD contact
Jens Tank, MD contact
Jens Jordan, MD study director
Hannover Medical School
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing beta-blocker (Metoprolol) and I(f)-blocker (ivabradine) in people with Postural Orthostatic Tachycardia Syndrome, run by Hannover Medical School at 2 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Mar 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Heidrun Mehling, MD (+49(0)30 ext. 94171296), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00865917, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2009.