SyncopeNCT00069693
Evaluation of Chronic Orthostatic Intolerance
An observational study of Syncope, run by National Institute of Neurological Disorders and Stroke (NINDS) at 3 sites in 2 countries.
Trial summary
This study will conduct tests with patients with primary chronic orthostatic intolerance (COI) to learn more about this disorder of the autonomic nervous system. Healthy normal volunteers and patients 18 years of age and older with COI may be eligible for this study. Read more about this study
- Who is it for?
- Ages 10 years and olderHealthy volunteers can take part
- Conditions the study is for
- Syncope
- How many people
- 200 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 26 Sep 2003to 5 Aug 2008
- Phase
- Observational
- 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 10 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- The subjects are patients with COI and adult healthy volunteers of similar age, gender, and body mass.
- Participation in this protocol is offered to people 18 years old or older, independently of gender, race, age, ethnicity, religion, or any other demographic or sociopolitical classifications.
- The subjects in the second off-site study are family members of the identified proband. Participation in this protocol is offered to people 18 years old or older, independently of gender, race, ethnicity, religion, or any other demographic or sociopolitical classifications.
- In the second off-site study, participation is also offered to subjects 10 to 17 years old, provided that appropriate informed consent/assent has been given by the subject and his/her parent or guardian.
Who cannot join
- Age: Minors younger than 18 years old are excluded, except for the off-site study. Advanced age does not constitute an exclusion criterion. For subjects more than 55 years old, carotid Doppler studies are done, and subjects with significant carotid disease (stenosis by atherosclerosis) are excluded. In the off-site study, minors younger than 10 years old are excluded. For the second off-site study, minors younger than 10 years old are excluded. Advanced age does not constitute an exclusion criterion. Except for the second off-site study, people less than 18 years old are excluded.
- Risk: A candidate subject is excluded if, in the judgment of the Principal Investigator or Clinical Director, protocol participation would place the 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 hepatic or renal failure, a history of tachyarrhythmias, symptomatic congestive heart failure, severe anemia, psychosis, refractory ventricular arrhythmias, symptomatic coronary heart disease, diabetes mellitus, hyperthyroidism, and allergy or sensitivity to iodinated contrast media or any of the planned drugs. A positive HIV rest 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. Examples are tricyclic antidepressants, anticoagulants, beta-adrenoceptor blockers, phenothiazines, barbiturates, monoamine oxidase inhibitors, acetaminophen, and alpha-adrenoceptor agonists or antagonists. Patients on one or more of these drugs are not excluded, if the drugs are tapered and discontinued before undergoing the clinical laboratory testing. Patients are not to discontinue any medications before the patient or the patient's doctor discusses this with the Principal Investigator. If it is decided that discontinuing medications would be unsafe, then the patient is excluded from the study. Patients with known or suspected allergy or hypersensitivity to any test drug are excluded. Patients unable to discontinue nicotine or alcohol for 24 hours prior to evaluation are excluded.
- Patients with chronic orthostatic intolerance often take several medications that could interfere with the scientific results of this protocol. Temporary discontinuation of medications as outpatients, even with the approval of the referring physician, introduces some risk. To maximize patient safety, we may admit patients for monitoring as inpatients while medications are tapered or stopped.
- In the second off-site study, subjects are tested while on their usual medications.
Show all 10Show fewer
- 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. 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. Subjects in the off-site study may continue their herbal medicines or dietary supplements.
- Practical Limitations: Patients in whom we feel it would be difficult to insert a catheter into a vein are excluded. Subjects who are not expected clinically to tolerate lying still during the procedures are excluded. In the second off-site study, if an i.v. cannot be placed, or the subject refuses to have an i.v. placed then a DNA sample may be obtained by buccal smear or obtaining saliva.
- Pregnancy: Pregnant or lactating women are excluded. In the second off-site study, pregnancy is not an exclusion criterion.
- 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
3 sites in 2 countries.
3 sites in 2 countries
Canada2 sites
Hospital Sacre-Coeur de Montreal
Montreal
University of Ottawa Heart Institute
Ottawa
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Clinical Laboratory Evaluation of Chronic Orthostatic Intolerance
This study will conduct tests with patients with primary chronic orthostatic intolerance (COI) to learn more about this disorder of the autonomic nervous system.
Healthy normal volunteers and patients 18 years of age and older with COI may be eligible for this study. Participants undergo one or more of the following tests and procedures:
Read more
- Blood studies, including arterial catheter insertion to measure blood pressure and collect arterial blood samples, blood flow studies using sensors applied to the skin and a pressure cuff around a limb, blood volume studies using injection of radioactively labeled human serum albumin and gene studies to look for genetic abnormalities associated with certain proteins.
- Imaging studies, including CT scan of the adrenal glands, heart ultrasound, and PET scanning.
- Electrocardiogram
- Microdialysis to measures levels of chemicals in the body fluid of certain tissues. A thin tube is inserted into the skin and a solution is passed through it. Chemicals in the body tissues enter the solution in the tube. The solution is collected and the chemical levels are measured.
- Neck suction. Neck suction is applied to test a reflex the brain uses to regulate blood pressure.
- Perometry. Limb volume is measured using an infrared light that moves up the limb.
- Quantitative sudomotor axon reflex test to evaluate an aspect of autonomic nervous system function. A small amount of a brain chemical (acetylcholine) is applied to the skin with a tiny amount of electricity, and the sweat in a nearby patch of skin is measured.
- Skin electrical conduction test using sensors on the skin to measure sweat production.
- Skin and core temperature measurements using sensors on the skin and in the ear canal.
- Tilt table test. The subject lies on a table, secured with straps around the chest and legs. Sensors are placed on the arms and chest to monitor blood pressure, pulse rate, and heart rhythm. A catheter is placed in a vein in each arm to collect blood samples and give drugs. Another catheter is placed in an artery to draw blood and monitor blood pressure. The subject is given an infusion of norepinephrine and epinephrine, and baseline measures and blood samples are taken. The table is tilted upright and more measurements and blood samples are taken at intervals for up to 30 minutes. The table is returned to a horizontal position and additional measurements and samples may be taken.
Drugs may be administered during the tests, including acetylcholine, epinephrine, and norepinephrine, radioactive chemicals used in imaging studies, and drugs that affect blood vessels, heart rate, and force of heart contractions.
Read the detailed description
This protocol is to identify and characterize distinct types of chronic orthostatic intolerance (COI). COI can be a manifestation of primary chronic autonomic failure, which is covered under a separate protocol. The present protocol concerns patients with COI who under resting conditions have intact sympathetic neurocirculatory function. COI can reflect different pathophysiologic mechanisms; until now, few studies have attempted to distinguish these mechanisms in individual patients. We hypothesize that results of clinical assessment and physiologic, chemical, pharmacologic, and imaging tests will reveal internally consistent patterns that distinguish particular forms of COI. We wish to determine the relative frequencies of these forms in a referral population. The first phase of testing is to identify sympathetic neurocirculatory failure, baroreflex failure, and secondary causes of COI (hypovolemia, excessive orthostatic venous pooling, or excessive orthostatic extravasation). In a subsequent inpatient phase, tilt table testing is done, with concurrent hemodynamic and chemical measurements, to confirm subtypes of postural tachycardia syndrome and neurocardiogenic syncope. The results of these evaluations will be used for stratification of specific, pathophysiologically defined diagnostic groups for therapeutic protocols. In an off-site study, we will evaluate members of a large family where COI seems to be transmitted as an autosomal dominant trait.
- Conditions
- Syncope
- Keywords
- Dysautonomia, Sympathetic Nervous System, Autonomic Nervous System, Syncope, Post Tachycardia Syndrome, POTS, Neurocardiogenic Syncope, Baroreflex, Norepinephrine, Epinephrine, Neurocardiology, Chronic Orthostatic Intolerance, COI, Healthy Volunteer, HV
- Medical subject headings
- Syncope, Autonomic Nervous System Diseases, Syncope, Vasovagal
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2003 (estimated)
- Study start26 Sep 2003
- Study completion5 Aug 2008
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 SyncopeStudies 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
- Observational
- Enrolment
- 200 participants
Sponsor and investigators
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00069693
- Sponsor's protocol ID
- 030314
- Other IDs
- 03-N-0314
- Status last verified
- 5 Aug 2008
- First submitted
- 29 Sep 2003
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Robertson D; New Collective Author. The epidemic of orthostatic tachycardia and orthostatic intolerance. Am J Med Sci. 1999 Feb;317(2):75-7. doi: 10.1097/00000441-199902000-00001. No abstract available.
PubMed 10037110Goldstein 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 12403667Furlan R, Jacob G, Snell M, Robertson D, Porta A, Harris P, Mosqueda-Garcia R; New Collective Author. Chronic orthostatic intolerance: a disorder with discordant cardiac and vascular sympathetic control. Circulation. 1998 Nov 17;98(20):2154-9. doi: 10.1161/01.cir.98.20.2154.
PubMed 9815870
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Laboratory Evaluation of Chronic Orthostatic Intolerance
- ClinicalTrials.gov ID
- NCT00069693
- Acronym / sponsor ID
- 030314
- Conditions
- Syncope
- Keywords
- Dysautonomia, Sympathetic Nervous System, Autonomic Nervous System, Syncope, Post Tachycardia Syndrome, POTS, Neurocardiogenic Syncope, Baroreflex
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 200 participants
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 26 Sep 2003
- Study completion
- 5 Aug 2008
- First posted
- 30 Sep 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 conduct tests with patients with primary chronic orthostatic intolerance (COI) to learn more about this disorder of the autonomic nervous system.
Healthy normal volunteers and patients 18 years of age and older with COI may be eligible for this study. Participants undergo one or more of the following tests and procedures:
- Blood studies, including arterial catheter insertion to measure blood pressure and collect arterial blood samples, blood flow studies using sensors applied to the skin and a pressure cuff around a limb, blood volume studies using injection of radioactively labeled human serum albumin and gene studies to look for genetic abnormalities associated with certain proteins.
- Imaging studies, including CT scan of the adrenal glands, heart ultrasound, and PET scanning.
- Electrocardiogram
- Microdialysis to measures levels of chemicals in the body fluid of certain tissues. A thin tube is inserted into the skin and a solution is passed through it. Chemicals in the body tissues enter the solution in the tube. The solution is collected and the chemical levels are measured.
- Neck suction. Neck suction is applied to test a reflex the brain uses to regulate blood pressure.
- Perometry. Limb volume is measured using an infrared light that moves up the limb.
- Quantitative sudomotor axon reflex test to evaluate an aspect of autonomic nervous system function. A small amount of a brain chemical (acetylcholine) is applied to the skin with a tiny amount of electricity, and the sweat in a nearby patch of skin is measured.
- Skin electrical conduction test using sensors on the skin to measure sweat production.
- Skin and core temperature measurements using sensors on the skin and in the ear canal.
- Tilt table test. The subject lies on a table, secured with straps around the chest and legs. Sensors are placed on the arms and chest to monitor blood pressure, pulse rate, and heart rhythm. A catheter is placed in a vein in each arm to collect blood samples and give drugs. Another catheter is placed in an artery to draw blood and monitor blood pressure. The subject is given an infusion of norepinephrine and epinephrine, and baseline measures and blood samples are taken. The table is tilted upright and more measurements and blood samples are taken at intervals for up to 30 minutes. The table is returned to a horizontal position and additional measurements and samples may be taken.
Drugs may be administered during the tests, including acetylcholine, epinephrine, and norepinephrine, radioactive chemicals used in imaging studies, and drugs that affect blood vessels, heart rate, and force of heart contractions.
Detailed description
This protocol is to identify and characterize distinct types of chronic orthostatic intolerance (COI). COI can be a manifestation of primary chronic autonomic failure, which is covered under a separate protocol. The present protocol concerns patients with COI who under resting conditions have intact sympathetic neurocirculatory function. COI can reflect different pathophysiologic mechanisms; until now, few studies have attempted to distinguish these mechanisms in individual patients. We hypothesize that results of clinical assessment and physiologic, chemical, pharmacologic, and imaging tests will reveal internally consistent patterns that distinguish particular forms of COI. We wish to determine the relative frequencies of these forms in a referral population. The first phase of testing is to identify sympathetic neurocirculatory failure, baroreflex failure, and secondary causes of COI (hypovolemia, excessive orthostatic venous pooling, or excessive orthostatic extravasation). In a subsequent inpatient phase, tilt table testing is done, with concurrent hemodynamic and chemical measurements, to confirm subtypes of postural tachycardia syndrome and neurocardiogenic syncope. The results of these evaluations will be used for stratification of specific, pathophysiologically defined diagnostic groups for therapeutic protocols. In an off-site study, we will evaluate members of a large family where COI seems to be transmitted as an autosomal dominant trait.
Study design
Who may qualify
- Ages
- 10 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- The subjects are patients with COI and adult healthy volunteers of similar age, gender, and body mass.
- Participation in this protocol is offered to people 18 years old or older, independently of gender, race, age, ethnicity, religion, or any other demographic or sociopolitical classifications.
- The subjects in the second off-site study are family members of the identified proband. Participation in this protocol is offered to people 18 years old or older, independently of gender, race, ethnicity, religion, or any other demographic or sociopolitical classifications.
- In the second off-site study, participation is also offered to subjects 10 to 17 years old, provided that appropriate informed consent/assent has been given by the subject and his/her parent or guardian.
Key exclusion criteria (10 listed)
- Age: Minors younger than 18 years old are excluded, except for the off-site study. Advanced age does not constitute an exclusion criterion. For subjects more than 55 years old, carotid Doppler studies are done, and subjects with significant carotid disease (stenosis by atherosclerosis) are excluded. In the off-site study, minors younger than 10 years old are excluded. For the second off-site study, minors younger than 10 years old are excluded. Advanced age does not constitute an exclusion criterion. Except for the second off-site study, people less than 18 years old are excluded.
- Risk: A candidate subject is excluded if, in the judgment of the Principal Investigator or Clinical Director, protocol participation would place the 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 hepatic or renal failure, a history of tachyarrhythmias, symptomatic congestive heart failure, severe anemia, psychosis, refractory ventricular arrhythmias, symptomatic coronary heart disease, diabetes mellitus, hyperthyroidism, and allergy or sensitivity to iodinated contrast media or any of the planned drugs. A positive HIV rest 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. Examples are tricyclic antidepressants, anticoagulants, beta-adrenoceptor blockers, phenothiazines, barbiturates, monoamine oxidase inhibitors, acetaminophen, and alpha-adrenoceptor agonists or antagonists. Patients on one or more of these drugs are not excluded, if the drugs are tapered and discontinued before undergoing the clinical laboratory testing. Patients are not to discontinue any medications before the patient or the patient's doctor discusses this with the Principal Investigator. If it is decided that discontinuing medications would be unsafe, then the patient is excluded from the study. Patients with known or suspected allergy or hypersensitivity to any test drug are excluded. Patients unable to discontinue nicotine or alcohol for 24 hours prior to evaluation are excluded.
- Patients with chronic orthostatic intolerance often take several medications that could interfere with the scientific results of this protocol. Temporary discontinuation of medications as outpatients, even with the approval of the referring physician, introduces some risk. To maximize patient safety, we may admit patients for monitoring as inpatients while medications are tapered or stopped.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
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 2 Jul 2017.
- Background: PubMed 10037110Robertson D; New Collective Author. The epidemic of orthostatic tachycardia and orthostatic intolerance. Am J Med Sci. 1999 Feb;317(2):75-7. doi: 10.1097/00000441-199902000-00001. No abstract available.
- 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 9815870Furlan R, Jacob G, Snell M, Robertson D, Porta A, Harris P, Mosqueda-Garcia R; New Collective Author. Chronic orthostatic intolerance: a disorder with discordant cardiac and vascular sympathetic control. Circulation. 1998 Nov 17;98(20):2154-9. doi: 10.1161/01.cir.98.20.2154.
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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.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Syncope, run by National Institute of Neurological Disorders and Stroke (NINDS) at 3 sites in 2 countries.
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 4 inclusion and 10 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 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Canada, 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.
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 NCT00069693, 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 2 Jul 2017; AzTrials last refreshed its copy on 1 Nov 2026.