Propranolol to Treat Fainting Due to Sympathoadrenal Imbalance
Information source: National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Neurocardiogenic Syncope
Intervention: Propranolol (Drug)
Phase: Phase 4
Sponsored by: National Institute of Neurological Disorders and Stroke (NINDS)
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.
Official title: Propranolol for Syncope With Sympathoadrenal Imbalance
Study design: Primary Purpose: Treatment
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
Minimum age: N/A.
Maximum age: N/A.
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.
Age: Minors younger than 18 years old are excluded. Advanced age does not constitute an
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
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
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
Locations and Contacts
National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Maryland 20892, United States
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. Review.
Goldstein 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.
Jacobs 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.
Starting date: May 2003
Last updated: March 3, 2008