Ignite Creation Date:
2024-05-06 @ 7:08 PM
Last Modification Date:
2024-10-26 @ 3:01 PM
Study NCT ID:
NCT05908760
Status:
RECRUITING
Last Update Posted:
2024-05-09
First Post:
2023-06-08
Brief Title:
CO2 Rebreathing in nOH A Proof-of-Concept Pilot Study
Sponsor:
University of Calgary
Organization:
University of Calgary
Study Overview
Official Title:
CO2 Rebreathing to Increase Blood Pressure in Neurogenic Orthostatic Hypotension A Proof-of-Concept Pilot Study
Status:
RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Neurogenic orthostatic hypotension nOH is a chronic condition associated with increased cardiovascular risk and reduced quality of life On standing patients with nOH experience a large reduction in blood pressure BP at least 2010mmHg but often much more which is often accompanied by debilitating symptoms and syncope A previous study unpublished showed that hypercapnia significantly increases standing BP in patients with nOH Human bodies naturally produce and exhale CO2 Rebreathe devices offer a simple cost-effective technology to increase arterial CO2 In brief rebreathe devices work by capturing expired CO2 which is then re-inhaled The net effect is a transient increase in CO2 A CO2 rebreathing device may offer a novel hemodynamic therapy for patients with nOH
This is a pilot proof-of-concept study to evaluate a CO2 rebreather to improve blood pressure and orthostatic tolerance in patients with nOH The hypothesis is that a rebreather will increase CO2 sufficiently enough to improve BP in patients with nOH
Male and female patients n28 will be asked to complete two randomized 70 head-up tilt HUT tests breathing either room air or using a CO2 rebreather Hemodynamics BP heart rate stroke volume brain blood flow and orthostatic symptoms will be assessed throughout Breath-by-breath data will include O2 CO2 respiration rate and tidal volume
The primary outcome measure will be the magnitude of the BP response ΔBP HUT - Supine during Room Air vs Hypercapnia The primary outcome will be compared between room air and hypercapnia using a paired t-test
This is a pilot proof-of-concept study to evaluate a CO2 rebreather to improve blood pressure and orthostatic tolerance in patients with nOH The hypothesis is that a rebreather will increase CO2 sufficiently enough to improve BP in patients with nOH
Male and female patients n28 will be asked to complete two randomized 70 head-up tilt HUT tests breathing either room air or using a CO2 rebreather Hemodynamics BP heart rate stroke volume brain blood flow and orthostatic symptoms will be assessed throughout Breath-by-breath data will include O2 CO2 respiration rate and tidal volume
The primary outcome measure will be the magnitude of the BP response ΔBP HUT - Supine during Room Air vs Hypercapnia The primary outcome will be compared between room air and hypercapnia using a paired t-test
Detailed Description:
BACKGROUND Neurogenic orthostatic hypotension nOH is a chronic condition associated with increased cardiovascular risk and reduced quality of life On standing patients with nOH experience a large reduction in blood pressure BP at least 2010mmHg but often much more which is often accompanied by debilitating symptoms and syncope nOH affects the elderly and patients with neurodegenerative diseases eg Parkinsons disease multiple system atrophy neuropathies eg diabetes and neural injury eg spinal cord injury
In healthy controls hypercapnia ie high CO2 increases in sympathetic nerve activity and BP Hypercapnia significantly increases supine and seated BP in patients with nOH and a previous study unpublished showed that hypercapnia significantly increases standing BP in patients with nOH
Human bodies naturally produce and exhale CO2 Rebreathe devices offer a simple cost-effective technology to increase arterial CO2 In brief rebreathe devices work by capturing expired CO2 which is then re-inhaled The net effect is a transient increase in CO2 A CO2 rebreathing device may offer a novel hemodynamic therapy for patients with nOH
OBJECTIVE This is a pilot proof-of-concept study to evaluate a CO2 rebreather to improve blood pressure and orthostatic tolerance in patients with nOH The study hypothesis is that a rebreather will increase CO2 sufficiently enough to improve BP in patients with nOH
METHODS Male and female patients n28 will be recruited from the Calgary Autonomic Investigation and Management Clinic
STUDY PROCEDURE Informed Consent The informed consent will be sent by email to the patients in advance The investigators will give each patient a chance to ask questions about the protocol and have these questions answered to their satisfaction Written informed consent will be documented prior to engaging in study-related procedures
Holding Pre-Existing Medications Participants will be asked to hold their clinical medications on the day of the study testing if possible but this will not be mandatory The investigators will make note of the medications used by each participant at the time of the study
Study Day Participants will be instrumented at least 2h post-prandial on an empty bladder Participants will be asked to abstain from alcohol caffeine and exercise for a period of 12 hours prior to testing Participants will be allowed to drink water on the morning of study Upon lab arrival a description of the study will be given and written informed consent will be attained if the individual chooses to participate in the study A member of the research team will ask participants about current medications and other disorders they many have as part of the study inclusionexclusion criteria The investigators will also review all other inclusionexclusion criteria for the study All study equipment will be introduced to the participant and then the investigators will begin to prepare for the study
Participants will be asked to lie supine on the tilt table during instrumentation Following instrumentation the study will begin with a 10-minute baseline in the supine position During this period the investigators will track blood pressure heart rate brain blood flow velocity fluid shifts and respiratory pattern using the following equipment
Finger and arm blood pressure cuffs
Skin electrodes to measure heart rate and fluid shifts
A Transcranial Doppler TCD which will use a band around the head with an ultrasound-like probe at the left andor right temple
Pulse oximeter on the finger to measure oxygen saturation
Participants will be fitted with a mouthpiece to breathing into The mouthpiece will be connected to a breathing bag that will capture the CO2 exhaled The mouthpiece will also be connected to a tube that will measure respiratory rate respiratory depth CO2 and O2
Following instrumentation participants will complete up to two 70 head-up tilt HUT tests while breathing either normal room air or while breathing with the rebreather Each HUT will last a maximum of 5 minutes and when participants are not upright the participants will be in the supine position Participants will be asked to breathe with the rebreather until the measured CO2 increases between 5-10mmHg Once CO2 is increased HUT will begin Participants will continue to breathe with the rebreather until the end of HUT
The two HUT tests will be randomized and will consist of
1 HUT with Room Air
2 HUT with ETCO2 levels increased 5-10mmHg above normal levels
The primary outcome measure will be the magnitude of the BP response ΔBP HUT - Supine during Room Air vs Hypercapnia The primary outcome will be compared between room air and hypercapnia using a paired t-test
In healthy controls hypercapnia ie high CO2 increases in sympathetic nerve activity and BP Hypercapnia significantly increases supine and seated BP in patients with nOH and a previous study unpublished showed that hypercapnia significantly increases standing BP in patients with nOH
Human bodies naturally produce and exhale CO2 Rebreathe devices offer a simple cost-effective technology to increase arterial CO2 In brief rebreathe devices work by capturing expired CO2 which is then re-inhaled The net effect is a transient increase in CO2 A CO2 rebreathing device may offer a novel hemodynamic therapy for patients with nOH
OBJECTIVE This is a pilot proof-of-concept study to evaluate a CO2 rebreather to improve blood pressure and orthostatic tolerance in patients with nOH The study hypothesis is that a rebreather will increase CO2 sufficiently enough to improve BP in patients with nOH
METHODS Male and female patients n28 will be recruited from the Calgary Autonomic Investigation and Management Clinic
STUDY PROCEDURE Informed Consent The informed consent will be sent by email to the patients in advance The investigators will give each patient a chance to ask questions about the protocol and have these questions answered to their satisfaction Written informed consent will be documented prior to engaging in study-related procedures
Holding Pre-Existing Medications Participants will be asked to hold their clinical medications on the day of the study testing if possible but this will not be mandatory The investigators will make note of the medications used by each participant at the time of the study
Study Day Participants will be instrumented at least 2h post-prandial on an empty bladder Participants will be asked to abstain from alcohol caffeine and exercise for a period of 12 hours prior to testing Participants will be allowed to drink water on the morning of study Upon lab arrival a description of the study will be given and written informed consent will be attained if the individual chooses to participate in the study A member of the research team will ask participants about current medications and other disorders they many have as part of the study inclusionexclusion criteria The investigators will also review all other inclusionexclusion criteria for the study All study equipment will be introduced to the participant and then the investigators will begin to prepare for the study
Participants will be asked to lie supine on the tilt table during instrumentation Following instrumentation the study will begin with a 10-minute baseline in the supine position During this period the investigators will track blood pressure heart rate brain blood flow velocity fluid shifts and respiratory pattern using the following equipment
Finger and arm blood pressure cuffs
Skin electrodes to measure heart rate and fluid shifts
A Transcranial Doppler TCD which will use a band around the head with an ultrasound-like probe at the left andor right temple
Pulse oximeter on the finger to measure oxygen saturation
Participants will be fitted with a mouthpiece to breathing into The mouthpiece will be connected to a breathing bag that will capture the CO2 exhaled The mouthpiece will also be connected to a tube that will measure respiratory rate respiratory depth CO2 and O2
Following instrumentation participants will complete up to two 70 head-up tilt HUT tests while breathing either normal room air or while breathing with the rebreather Each HUT will last a maximum of 5 minutes and when participants are not upright the participants will be in the supine position Participants will be asked to breathe with the rebreather until the measured CO2 increases between 5-10mmHg Once CO2 is increased HUT will begin Participants will continue to breathe with the rebreather until the end of HUT
The two HUT tests will be randomized and will consist of
1 HUT with Room Air
2 HUT with ETCO2 levels increased 5-10mmHg above normal levels
The primary outcome measure will be the magnitude of the BP response ΔBP HUT - Supine during Room Air vs Hypercapnia The primary outcome will be compared between room air and hypercapnia using a paired t-test
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None