Neurocardiogenic SyncopePhase 4NCT00060866
Propranolol to Treat Fainting Due to Sympathoadrenal Imbalance
A Phase 4 study testing Propranolol in people with Neurocardiogenic Syncope, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
This study will examine the effectiveness of the drug propranolol in preventing fainting in patients with sympathoadrenal imbalance (SAI). SAI is a particular pattern of nervous system and chemical responses in which the blood vessels in skeletal muscles do not remain constricted appropriately during standing for a… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Neurocardiogenic Syncope
- What is being tested?
- Propranolol
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- May 2003to Mar 2005
- Phase
- Phase 4
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Subjects are patients referred for evaluation of chronic orthostatic intolerance. Patients enter into the therapeutic trial after they are determined to have NCS with SAI in a screening evaluation. Participation in this protocol is offered to individuals 18 years old or older, independently of gender, race, advanced age, ethnicity, religion, or any demographic or sociopolitical classifications.
Who cannot join
- Age: Minors younger than 18 years old are excluded. Advanced age does not constitute an exclusion criterion.
- Risk: A candidate subject is excluded if, in the judgement of the Principal Investigator or Clinical Director, protocol participation would place the subject at subject at substantially increased acute medical risk. This includes the risks associated with air travel to the NIH. A candidate subject is excluded if, in the opinion of the Principal Investigator or Clinical Director, the medical risk outweighs the potential scientific benefit.
- Disqualifying Conditions: A candidate subject is excluded if there is a disqualifying condition. Examples of disqualifying conditions are history of asthma or chronic obstructive pulmonary disease requiring bronchodilators, hepatic or renal failure, atrioventricular block of any degree, bradycardia, symptomatic congestive heart failure, severe anemia, psychosis, refractory ventricular arrhythmias, symptomatic coronary heart disease, insulin-dependent diabetes mellitus, Wolff-Parkinson-White syndrome, and peripheral vascular disease. Patients with known or suspected allergy or hypersensitivity to propranolol are excluded from this study. A positive HIV test result does not necessarily exclude a patient from participating.
- Medications: A candidate subject is excluded if clinical considerations require that the patient continue treatment with a drug likely to interfere with the scientific results. Patients who must take medications daily in the following categories are excluded: anticoagulants, tricyclic, antidepressants, barbiturates, aspirin, acetaminophen, insulin, bronchodilators. Patients unable to discontinue nicotine, caffeine, or alcohol temporarily are excluded. Patients with chronic alcohol intake are excluded. Patients are not to discontinue any medications before the patient or the patient's doctor discusses this with the Principal Investigator, an Associate Investigator, or Research Nurse. If it is decided that discontinuing medications would be unsafe, then the patient is excluded from the study.
- Herbal Medicines and Dietary Supplements: Certain herbal medicines or dietary supplements are known or suspected to interfere with the experimental results, and such herbal medicines or dietary supplements must be discontinued before enrollment in the study. For many herbal medicines or dietary supplements, the mechanisms of action and therefore the possible effects on the experimental results are unknown. In cases where the subjects wish to continue their herbal medicines or dietary supplements while on study, and search of the available medical literature fails to identify effects that are known or expected to interfere with the experimental results, then the subjects may participate.
- Practical Limitations: Patients in whom we feel it would be difficult to technically to carry out the testing procedures are excluded.
- Pregnancy: Pregnant or lactating women are excluded. A blood test for pregnancy will be conducted on women of childbearing potential, before intake evaluation and also before each drug treatment phase. During the course of the protocol, subjects who are women of childbearing potential will be advised to practice adequate contraception.
- Termination of Participation: Subjects may refuse certain tests or procedures, or may terminate participation early, without loss of benefits to which they were previously entitled. The Investigators may also exclude a subject from further participation, such as in the event of known or suspect falsification of medical history information or refusal to undergo planned tests or procedures, without loss of benefits to which the subject was previously entitled.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Neurological Disorders and Stroke (NINDS)
Bethesda, Maryland, 20892
About this study
Official title: Propranolol for Syncope With Sympathoadrenal Imbalance
This study will examine the effectiveness of the drug propranolol in preventing fainting in patients with sympathoadrenal imbalance (SAI). SAI is a particular pattern of nervous system and chemical responses in which the blood vessels in skeletal muscles do not remain constricted appropriately during standing for a long time. This can lower blood pressure and cause fainting. Propranolol Inderal (registered trademark) is a Food and Drug Administration-approved drug that belongs to a class of drugs called beta-blockers. These drugs slow the heart rate and maintain blood pressure in certain situations.
Patients 18 years of age and older with SAI may be eligible for this study. Screening includes a tilt table test, described below, to determine if the patient has a particular chemical pattern in the blood.
Read more
Patients enrolled in the study take propranolol pills in increasing doses during the first week of the study to determine the proper dose for the individual. Then, the drug is stopped until the experimental phase of the study begins. In this phase, patients are randomly assigned to take either propranolol or placebo (look-alike pill with no active ingredient) for 4 days. On the fourth day, the patient undergoes a tilt table test to determine whether the treatment affects the patient's ability to tolerate tilt. For this test, the patient lies on a padded table with a motorized tilt mechanism that can move the patient from a flat position to an upright position in about 10 seconds. The patient remains upright for up to 45 minutes while the following measurements are taken:
- Arterial blood pressure monitoring and arterial blood sampling. A catheter (thin, plastic tube) is inserted into an artery in the elbow crease area of the arm or the wrist. This catheter allows continuous blood pressure monitoring and sampling of arterial (oxygenated) blood during the tilt test.
- Venous blood sampling and measurement of epinephrine and norepinephrine release. A catheter is inserted into a vein in each arm, one to collect venous (deoxygenated) blood samples, and the other to inject radioactive epinephrine (adrenaline) and norepinephrine (noradrenaline). These radioactive drugs, or ,tracers, allow measurement of the rate of release of the body's own norepinephrine and epinephrine into the bloodstream.
- Physiologic measurements. Blood pressure, heart rate, and EKG are measured continuously during the tilt test session, and blood flows and skin electrical conduction are measured intermittently. Blood flow is measured using sensors applied to the skin and a blood pressure cuff around the limb. For skin blood flow measurements, a laser beam scans the skin surface. The skin electrical conduction test measures how well the skin conducts electricity. This is measured through sensors placed on the fingers or other sites.
The effects of the test drug are allowed to wear off for 1 week, after which the entire tilt test procedure is repeated. Patients who were given propranolol for the first test session take placebo for the repeat session, and those who were given placebo take propranolol.
Read the detailed description
This protocol is to evaluate treatment with oral propranolol for a particular form of neurocardiogenic syncope (NCS), characterized by a neuroendocrine pattern called, sympathoadrenal imbalance, (SAI). In SAI, plasma epinephrine levels increase progressively and to a greater extent than do plasma norepinephrine levels, before development of NCS. The SAI pattern is associated with skeletal muscle vasodilation, which also precedes NCS. We hypothesize that increased occupation of beta-2 adrenoceptors in skeletal muscle by high circulating epinephrine levels precipitates a neurocirculatory positive feedback loop leading to NCS. In this protocol we test this hypothesis using the non-selective beta-adrenoceptor blocker, propranolol. We predict that in patients with previously documented SAI and tilt-evoked NCS, propranolol treatment will improve orthostatic tolerance during follow-up tilt table testing, in a randomized, crossover-design, placebo-controlled, double-blind trial. The main department measures are occurrence of tilt-induced NCS, duration of tilt tolerance, hemodynamic and neurochemical indices of SAL, and patient questionnaire reports.
- Conditions
- Neurocardiogenic Syncope
- Being tested
- Propranolol
- Keywords
- Beta-Adrenoceptors, Beta-Adrenoceptor Blocker, Neurocardiogenic Syncope, Chronic Orthostatic Intolerance, Neurocardiogenic, Dysautonomia, Autonomic Nervous System, Nurocardiogenic Syncope, NCS, Sympathoadrenal Imbalance, SAI, Orthostatic Intolerance
- Medical subject headings
- Syncope, Vasovagal, Autonomic Nervous System Diseases, Orthostatic Intolerance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PropranololDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2003 (estimated)
- Study startMay 2003
- Study completionMar 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Neurocardiogenic SyncopeStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Enrolment
- 24 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00060866
- Sponsor's protocol ID
- 030182
- Other IDs
- 03-N-0182
- Status last verified
- Mar 2005
- First submitted
- 14 May 2003
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Robertson RM, Medina E, Shah N, Furlan R, Mosqueda-Garcia R. Neurally mediated syncope: pathophysiology and implications for treatment. Am J Med Sci. 1999 Feb;317(2):102-9. doi: 10.1097/00000441-199902000-00004.
PubMed 10037113Goldstein DS, Holmes C, Frank SM, Dendi R, Cannon RO 3rd, Sharabi Y, Esler MD, Eisenhofer G. Cardiac sympathetic dysautonomia in chronic orthostatic intolerance syndromes. Circulation. 2002 Oct 29;106(18):2358-65. doi: 10.1161/01.cir.0000036015.54619.b6.
PubMed 12403667Jacobs MC, Goldstein DS, Willemsen JJ, Smits P, Thien T, Dionne RA, Lenders JW. Neurohumoral antecedents of vasodepressor reactions. Eur J Clin Invest. 1995 Oct;25(10):754-61. doi: 10.1111/j.1365-2362.1995.tb01954.x.
PubMed 8557062
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Propranolol for Syncope With Sympathoadrenal Imbalance
- ClinicalTrials.gov ID
- NCT00060866
- Acronym / sponsor ID
- 030182
- Conditions
- Neurocardiogenic Syncope
- Keywords
- Beta-Adrenoceptors, Beta-Adrenoceptor Blocker, Neurocardiogenic Syncope, Chronic Orthostatic Intolerance, Neurocardiogenic, Dysautonomia, Autonomic Nervous System, Nurocardiogenic Syncope
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- May 2003
- Study completion
- Mar 2005
- First posted
- 15 May 2003 (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.
This study will examine the effectiveness of the drug propranolol in preventing fainting in patients with sympathoadrenal imbalance (SAI). SAI is a particular pattern of nervous system and chemical responses in which the blood vessels in skeletal muscles do not remain constricted appropriately during standing for a long time. This can lower blood pressure and cause fainting. Propranolol Inderal (registered trademark) is a Food and Drug Administration-approved drug that belongs to a class of drugs called beta-blockers. These drugs slow the heart rate and maintain blood pressure in certain situations.
Patients 18 years of age and older with SAI may be eligible for this study. Screening includes a tilt table test, described below, to determine if the patient has a particular chemical pattern in the blood.
Patients enrolled in the study take propranolol pills in increasing doses during the first week of the study to determine the proper dose for the individual. Then, the drug is stopped until the experimental phase of the study begins. In this phase, patients are randomly assigned to take either propranolol or placebo (look-alike pill with no active ingredient) for 4 days. On the fourth day, the patient undergoes a tilt table test to determine whether the treatment affects the patient's ability to tolerate tilt. For this test, the patient lies on a padded table with a motorized tilt mechanism that can move the patient from a flat position to an upright position in about 10 seconds. The patient remains upright for up to 45 minutes while the following measurements are taken:
- Arterial blood pressure monitoring and arterial blood sampling. A catheter (thin, plastic tube) is inserted into an artery in the elbow crease area of the arm or the wrist. This catheter allows continuous blood pressure monitoring and sampling of arterial (oxygenated) blood during the tilt test.
- Venous blood sampling and measurement of epinephrine and norepinephrine release. A catheter is inserted into a vein in each arm, one to collect venous (deoxygenated) blood samples, and the other to inject radioactive epinephrine (adrenaline) and norepinephrine (noradrenaline). These radioactive drugs, or ,tracers, allow measurement of the rate of release of the body's own norepinephrine and epinephrine into the bloodstream.
- Physiologic measurements. Blood pressure, heart rate, and EKG are measured continuously during the tilt test session, and blood flows and skin electrical conduction are measured intermittently. Blood flow is measured using sensors applied to the skin and a blood pressure cuff around the limb. For skin blood flow measurements, a laser beam scans the skin surface. The skin electrical conduction test measures how well the skin conducts electricity. This is measured through sensors placed on the fingers or other sites.
The effects of the test drug are allowed to wear off for 1 week, after which the entire tilt test procedure is repeated. Patients who were given propranolol for the first test session take placebo for the repeat session, and those who were given placebo take propranolol.
Detailed description
This protocol is to evaluate treatment with oral propranolol for a particular form of neurocardiogenic syncope (NCS), characterized by a neuroendocrine pattern called, sympathoadrenal imbalance, (SAI). In SAI, plasma epinephrine levels increase progressively and to a greater extent than do plasma norepinephrine levels, before development of NCS. The SAI pattern is associated with skeletal muscle vasodilation, which also precedes NCS. We hypothesize that increased occupation of beta-2 adrenoceptors in skeletal muscle by high circulating epinephrine levels precipitates a neurocirculatory positive feedback loop leading to NCS. In this protocol we test this hypothesis using the non-selective beta-adrenoceptor blocker, propranolol. We predict that in patients with previously documented SAI and tilt-evoked NCS, propranolol treatment will improve orthostatic tolerance during follow-up tilt table testing, in a randomized, crossover-design, placebo-controlled, double-blind trial. The main department measures are occurrence of tilt-induced NCS, duration of tilt tolerance, hemodynamic and neurochemical indices of SAL, and patient questionnaire reports.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- Subjects are patients referred for evaluation of chronic orthostatic intolerance. Patients enter into the therapeutic trial after they are determined to have NCS with SAI in a screening evaluation. Participation in this protocol is offered to individuals 18 years old or older, independently of gender, race, advanced age, ethnicity, religion, or any demographic or sociopolitical classifications.
Key exclusion criteria (8 listed)
- Age: Minors younger than 18 years old are excluded. Advanced age does not constitute an exclusion criterion.
- Risk: A candidate subject is excluded if, in the judgement of the Principal Investigator or Clinical Director, protocol participation would place the subject at subject at substantially increased acute medical risk. This includes the risks associated with air travel to the NIH. A candidate subject is excluded if, in the opinion of the Principal Investigator or Clinical Director, the medical risk outweighs the potential scientific benefit.
- Disqualifying Conditions: A candidate subject is excluded if there is a disqualifying condition. Examples of disqualifying conditions are history of asthma or chronic obstructive pulmonary disease requiring bronchodilators, hepatic or renal failure, atrioventricular block of any degree, bradycardia, symptomatic congestive heart failure, severe anemia, psychosis, refractory ventricular arrhythmias, symptomatic coronary heart disease, insulin-dependent diabetes mellitus, Wolff-Parkinson-White syndrome, and peripheral vascular disease. Patients with known or suspected allergy or hypersensitivity to propranolol are excluded from this study. A positive HIV test result does not necessarily exclude a patient from participating.
- Medications: A candidate subject is excluded if clinical considerations require that the patient continue treatment with a drug likely to interfere with the scientific results. Patients who must take medications daily in the following categories are excluded: anticoagulants, tricyclic, antidepressants, barbiturates, aspirin, acetaminophen, insulin, bronchodilators. Patients unable to discontinue nicotine, caffeine, or alcohol temporarily are excluded. Patients with chronic alcohol intake are excluded. Patients are not to discontinue any medications before the patient or the patient's doctor discusses this with the Principal Investigator, an Associate Investigator, or Research Nurse. If it is decided that discontinuing medications would be unsafe, then the patient is excluded from the study.
- Herbal Medicines and Dietary Supplements: Certain herbal medicines or dietary supplements are known or suspected to interfere with the experimental results, and such herbal medicines or dietary supplements must be discontinued before enrollment in the study. For many herbal medicines or dietary supplements, the mechanisms of action and therefore the possible effects on the experimental results are unknown. In cases where the subjects wish to continue their herbal medicines or dietary supplements while on study, and search of the available medical literature fails to identify effects that are known or expected to interfere with the experimental results, then the subjects may participate.
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 |
|---|---|---|
| Propranolol | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 10037113Robertson RM, Medina E, Shah N, Furlan R, Mosqueda-Garcia R. Neurally mediated syncope: pathophysiology and implications for treatment. Am J Med Sci. 1999 Feb;317(2):102-9. doi: 10.1097/00000441-199902000-00004.
- Background: PubMed 12403667Goldstein DS, Holmes C, Frank SM, Dendi R, Cannon RO 3rd, Sharabi Y, Esler MD, Eisenhofer G. Cardiac sympathetic dysautonomia in chronic orthostatic intolerance syndromes. Circulation. 2002 Oct 29;106(18):2358-65. doi: 10.1161/01.cir.0000036015.54619.b6.
- Background: PubMed 8557062Jacobs MC, Goldstein DS, Willemsen JJ, Smits P, Thien T, Dionne RA, Lenders JW. Neurohumoral antecedents of vasodepressor reactions. Eur J Clin Invest. 1995 Oct;25(10):754-61. doi: 10.1111/j.1365-2362.1995.tb01954.x.
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Propranolol in people with Neurocardiogenic Syncope, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
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 1 inclusion and 8 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: finished, as of the sponsor's last update on 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00060866, which also lists 3 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 4 Mar 2008.