Chemoreflex and Baroreflex Alterations Causing Postural Tachycardia Syndrome With Orthostatic Hyperpnea and Hypocapnia

NCT ID: NCT05923840

Last Updated: 2023-06-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-09-23

Study Completion Date

2024-08-31

Brief Summary

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Postural tachycardia syndrome (POTS) is the most common chronic cause of postural lightheadedness, and upright confusion afflicting many Americans, mostly young women. Many POTS patients hyperventilate by increasing their depth of breathing that produces tachycardia, alters blood flow and blood pooling in the body and importantly reduces brain blood flow causing "brain fog". In this proposal the investigators will demonstrate in young women that abnormal repeated brief impairment of blood pressure and brain flow just after standing sensitizes the body's oxygen sensor in POTS to respond as if it were in a low oxygen environment causing hyperventilation and its consequences. In this project the investigators will use various drugs that will help to understand the mechanisms that cause POTS in this unique subset of POTS patients who hyperventilate.

Detailed Description

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The Investigators will compare results from female POTS patients, free of known pulmonary or sleep disorders aged 15 to 39 years with, and without orthostatic hyperpneic hypocapnia, to healthy female volunteers with the following two (2) specific aims:

1. To test poikilocapnic (allowing carbon dioxide (CO2) to vary) orthostatic cardiorespiratory responses to determine whether prolonged initial orthostatic hypotension (IOH) precedes upright hypocapnia in hyperpneic POTS but not in controls or non-hyperpneic POTS. Subjects are instrumented for cerebral blood flow, respiratory and hemodynamic measurements, investigating splanchnic blood flow by indocyanine green infusion, and measuring changes of CBV, regional blood volumes, and cardiac output (CO) by impedance plethysmography during a 10 min stand to quantify IOH, and a 10 min tilt test to 70⁰ to quantitate cardiorespiratory changes. These changes during tilt stratify hyperpneic and non-hyperpneic POTS.
2. To test if chemoreflex sensitization of ventilation and sympathetic activity (by microneurography) are abnormal when supine and tilted upright at 45o and how that interacts with Oxford measured cardiovagal and sympathetic baroreflexes under controlled gas conditions which are: isocapnic hypoxia and isocapnic hyperoxia to measure carotid body reflex; hyperoxic isocapnia and hyperoxic hypercapnia to measure central chemoreflexes. Hyperoxia silences peripheral chemoreceptors and will normalize baroreflex and tilt responses.

Conditions

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Postural Orthostatic Tachycardia Syndrome Hypocapnia Hyperventilation

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

The investigators will compare results from female POTS patients, free of known pulmonary or sleep disorders aged 15 to 39 years with, and without orthostatic hyperpneic hypocapnia, to healthy female volunteers.
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Female Postural Tachycardia Syndrome (POTS) patients without orthostatic hyperpneic hypocapnia

Female POTS patients without orthostatic hyperpneic hypocapnia identified by tilt table testing and respiratory monitoring.

Group Type ACTIVE_COMPARATOR

Chemoreflex Testing

Intervention Type DIAGNOSTIC_TEST

The carotid body chemoreflex can be tested by holding carbon dioxide (CO2) constant (isocapnic) and applying hypoxia and hyperoxia. Measurements are then made of expiratory minute volume and of sympathetic activity. The central chemoreflex measures isocapnic and hypercapnic responses in the presence of hyperoxia to suppress the carotid body chemoreflex.

Baroreflex testing

Intervention Type DIAGNOSTIC_TEST

Baroreceptors are measured by the change of heart rate (HR) and sympathetic activity with changing blood pressure using the modified Oxford technique. Blood pressure is lowered an amount by a bolus of sodium nitroprusside and then raised by a bolus of phenylephrine. When standing baroreflexes are activated and the investigators will measure chemoreflex activity upright to see how baroreflex effects the chemoreflexes. Similarly chemoreflexes affect the baroreflexes best observed when the patients are supine.

Orthostatic stress testing

Intervention Type DIAGNOSTIC_TEST

Orthostatic Stress tests are administered in two forms: a standing test to evoke the initial orthostatic hypotensive response that sensitizes and triggers the carotid body chemoreflex by intermittent stagnant ischemia. And the 70 degree upright tilt test that best identifies causal changes in regional blood volumes and flows and in respiratory patterns of hyperpneic hypocapnia.

Female POTS patients with orthostatic hyperpneic hypocapnia

Female POTS patients without orthostatic hyperpneic hypocapnia identified by tilt table testing and respiratory monitoring.

Group Type ACTIVE_COMPARATOR

Chemoreflex Testing

Intervention Type DIAGNOSTIC_TEST

The carotid body chemoreflex can be tested by holding carbon dioxide (CO2) constant (isocapnic) and applying hypoxia and hyperoxia. Measurements are then made of expiratory minute volume and of sympathetic activity. The central chemoreflex measures isocapnic and hypercapnic responses in the presence of hyperoxia to suppress the carotid body chemoreflex.

Baroreflex testing

Intervention Type DIAGNOSTIC_TEST

Baroreceptors are measured by the change of heart rate (HR) and sympathetic activity with changing blood pressure using the modified Oxford technique. Blood pressure is lowered an amount by a bolus of sodium nitroprusside and then raised by a bolus of phenylephrine. When standing baroreflexes are activated and the investigators will measure chemoreflex activity upright to see how baroreflex effects the chemoreflexes. Similarly chemoreflexes affect the baroreflexes best observed when the patients are supine.

Orthostatic stress testing

Intervention Type DIAGNOSTIC_TEST

Orthostatic Stress tests are administered in two forms: a standing test to evoke the initial orthostatic hypotensive response that sensitizes and triggers the carotid body chemoreflex by intermittent stagnant ischemia. And the 70 degree upright tilt test that best identifies causal changes in regional blood volumes and flows and in respiratory patterns of hyperpneic hypocapnia.

Healthy Female vounteers

Healthy Female vounteers

Group Type ACTIVE_COMPARATOR

Chemoreflex Testing

Intervention Type DIAGNOSTIC_TEST

The carotid body chemoreflex can be tested by holding carbon dioxide (CO2) constant (isocapnic) and applying hypoxia and hyperoxia. Measurements are then made of expiratory minute volume and of sympathetic activity. The central chemoreflex measures isocapnic and hypercapnic responses in the presence of hyperoxia to suppress the carotid body chemoreflex.

Baroreflex testing

Intervention Type DIAGNOSTIC_TEST

Baroreceptors are measured by the change of heart rate (HR) and sympathetic activity with changing blood pressure using the modified Oxford technique. Blood pressure is lowered an amount by a bolus of sodium nitroprusside and then raised by a bolus of phenylephrine. When standing baroreflexes are activated and the investigators will measure chemoreflex activity upright to see how baroreflex effects the chemoreflexes. Similarly chemoreflexes affect the baroreflexes best observed when the patients are supine.

Orthostatic stress testing

Intervention Type DIAGNOSTIC_TEST

Orthostatic Stress tests are administered in two forms: a standing test to evoke the initial orthostatic hypotensive response that sensitizes and triggers the carotid body chemoreflex by intermittent stagnant ischemia. And the 70 degree upright tilt test that best identifies causal changes in regional blood volumes and flows and in respiratory patterns of hyperpneic hypocapnia.

Interventions

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Chemoreflex Testing

The carotid body chemoreflex can be tested by holding carbon dioxide (CO2) constant (isocapnic) and applying hypoxia and hyperoxia. Measurements are then made of expiratory minute volume and of sympathetic activity. The central chemoreflex measures isocapnic and hypercapnic responses in the presence of hyperoxia to suppress the carotid body chemoreflex.

Intervention Type DIAGNOSTIC_TEST

Baroreflex testing

Baroreceptors are measured by the change of heart rate (HR) and sympathetic activity with changing blood pressure using the modified Oxford technique. Blood pressure is lowered an amount by a bolus of sodium nitroprusside and then raised by a bolus of phenylephrine. When standing baroreflexes are activated and the investigators will measure chemoreflex activity upright to see how baroreflex effects the chemoreflexes. Similarly chemoreflexes affect the baroreflexes best observed when the patients are supine.

Intervention Type DIAGNOSTIC_TEST

Orthostatic stress testing

Orthostatic Stress tests are administered in two forms: a standing test to evoke the initial orthostatic hypotensive response that sensitizes and triggers the carotid body chemoreflex by intermittent stagnant ischemia. And the 70 degree upright tilt test that best identifies causal changes in regional blood volumes and flows and in respiratory patterns of hyperpneic hypocapnia.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* The investigators will recruit female POTS cases (N=80) and healthy female control subjects (N=40) aged 15-39 years, matched for BMI. POTS is a disease in which 80-90% are females. Therefore, the investigators will only recruit female POTS patients and controls.

Exclusion Criteria

* Any subjects with systemic disease or who cannot stop taking prescribed medications for at least 2 weeks prior to study.
Minimum Eligible Age

15 Years

Maximum Eligible Age

39 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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New York Medical College

OTHER

Sponsor Role lead

Responsible Party

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Marvin Medow

Professor of Pediatrics

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Marvin S Medow, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

New York Medical College

Locations

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NewYork Medical College

Hawthorne, New York, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Marvin S Medow, Ph.D.

Role: CONTACT

914-594-2848

Julian M Stewart, M.D., Ph.D.

Role: CONTACT

914-594-2849

Facility Contacts

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Marvin S Medow, Ph.D.

Role: primary

914-594-2848

Julian M Stewart, M.D.,Ph.D.

Role: backup

914-594=2849

Other Identifiers

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R56HL162752

Identifier Type: NIH

Identifier Source: org_study_id

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