HemorrhagePPT2NCT05983744
Pulsatile Perfusion Therapy Phase II
A study testing 0.1 Hz PPT and 0.05 Hz PPT in people with Hemorrhage, run by Caroline Rickards at 1 site in United States.
Trial summary
Individuals who suffer from a stroke, cardiac arrest, or traumatic bleeding (hemorrhage) injuries often have compromised blood flow and oxygen to the brain which can lead to the death of brain cells, and if the patient survives, subsequent difficulty in thinking and performing tasks of daily living. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Hemorrhage
- What is being tested?
- 0.1 Hz PPT and 0.05 Hz PPT
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Feb 2020to 17 Dec 2021
- Phase
- Interventional
- 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 18 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Aged 18 to 40 years
- Non-tobacco/nicotine users (e.g., cigarettes (including electronic cigarettes), chewing tobacco, nicotine gum or patches)
- Systolic arterial pressure <140 mmHg; diastolic arterial pressure <90 mmHg
- Normal 12-lead ECG (reviewed by a physician)
- Normal clinical results from a medical exam reviewed by a board certified physician (e.g., General Health Questionnaire - see attached document)
- Easily visualized internal carotid and vertebral arteries (via Doppler ultrasound) for accurate measurement of velocity and diameter.
- Body mass index (BMI) <30 kg/m2 unless athletic/muscular build; calculation = body weight (kg)/height (m2); this criteria is used to ensure subjects will fit inside the LBNP chamber
- Females only: documentation of a negative pregnancy test prior to the familiarization and experimental sessions
Who cannot join
- Age <18 or >40 years
- Use of tobacco/nicotine within the last 6 months (e.g., cigarettes (including electronic cigarettes), chewing tobacco, nicotine gum or patches)
- Body mass index (BMI) >30 kg/m2 unless athletic/muscular build; calculation = body weight (kg)/height (m2)
- Not abstaining from the following 24 hours prior to the experimental session: exercise, alcoholic substances, prescription or non-prescription medications (unless cleared by the medical screener), dietary supplements, herbal medications, caffeinated substances (including coffee, tea (iced or hot), caffeinated energy drinks or sodas).
- Inability to visualize the internal carotid and vertebral arteries (via Doppler ultrasound) for accurate measurement of velocity and diameter.
- Positive pregnancy test
Show all 26Show fewer
- Post-menopausal females
- Females with an erratic/irregular menstrual cycle
- Use of prescription drugs, non-prescription drugs or herbal medicines known to alter cardiovascular, autonomic, or cerebrovascular function unless cleared prior to the study
- Use of anti-hypertensive medications
- Use of beta blockers
- Frequent use of bronchodilators (occasional use, i.e. seasonally, is allowable)
- Use of anti-coagulant therapy
- Use of non-contraceptive related hormone therapy
- Current or past history of hyperthyroidism, or other thyroid hormone-related disease
- Signs of cardiovascular abnormalities (e.g., resting systolic blood pressure >140mmHg or diastolic blood pressure >90mmHg; abnormal 12-lead ECG)
- History of cerebrovascular abnormalities (e.g., prior stroke, transient ischemic attacks, epilepsy)
- Known history of atherosclerosis of the carotid arteries (i.e., plaque formation)
- History of concussion and or other loss of consciousness within the preceding month
- Autonomic dysfunction (e.g., Shy-Drager Syndrome, Bradbury-Eggleston syndrome, sinus arrhythmia, idiopathic orthostatic hypotension, fainting disorder)
- Respiratory illnesses (e.g., chronic asthma (including exercise-induced asthma), Chronic Obstructive Pulmonary Disease, Reactive Airway Disease)
- History of anaphylaxis
- Known allergies to medications or other substances (e.g. latex) unless cleared prior to the study
- History of pre-syncopal/syncopal episodes or orthostatic hypotension
- Donated blood within the last 60 days
- History or family history of abnormal blood clotting, clots in deep veins in the legs or pelvis, or blood clots to the lungs aa) Known or suspected abdominal hernia bb) History of alcohol or drug abuse which inhibits the subject's ability to complete this study cc) Known depression, anxiety, or any other mental health issue which inhibits the subject's ability to complete this study dd) Known claustrophobia ee) Previous positive diagnosis of COVID-19
Trial locations and contacts
1 site in 1 country.
United States1 site
University of North Texas Health Science Center
Fort Worth, Texas, 76107
About this study
Official title: Pulsatile Perfusion Therapy Phase II: A Novel Approach for Improving Cerebral Tissue Blood Flow and Oxygenation
Individuals who suffer from a stroke, cardiac arrest, or traumatic bleeding (hemorrhage) injuries often have compromised blood flow and oxygen to the brain which can lead to the death of brain cells, and if the patient survives, subsequent difficulty in thinking and performing tasks of daily living. Traditionally, delivery of a constant flow of blood to the brain has been thought to be the most important factor for the survival of brain cells. In this study, a novel intervention will be assessed called "pulsatile perfusion therapy", delivering blood flow in a slow pulsing pattern. It is anticipated this intervention will improve brain blood flow and oxygenation during these serious clinical events.
There is a specific interest in whether delivery of brain blood flow with a slow pulsatile pattern will improve oxygenation of brain tissue, particularly when the brain is challenged under low oxygen (hypoxia) and low volume (hypovolemia) conditions, simulating stroke, cardiac arrest, and hemorrhage. A technique called oscillatory lower body negative pressure (OLBNP) will be used in healthy human participants, facilitating delivery of blood flow to the brain with different pulsing patterns. This technique will allow for determination of the ideal pattern of brain blood flow that improves oxygenation of the brain tissue. Measurements will be made of substances in the blood that may be released with pulsatile flow which act on the blood vessels to increase flow and delivery of oxygen.
Read the detailed description
Hemorrhage due to trauma is one of the leading causes of morbidity and mortality worldwide in both the civilian and military settings. A major factor contributing to death and disability from severe blood loss is poor tissue perfusion and oxygenation of the vital organs. Traditionally, protection of absolute cerebral blood flow (CBF) has been deemed the most important factor in maintaining perfusion and oxygenation. In recent years, it has been shown that low frequency (LF, ~0.1 Hz) pulsatile CBF is associated with increased tolerance to simulated hemorrhage in healthy human subjects, despite ≥30% reductions in absolute CBF. The underlying mechanism for this improvement in tolerance is unclear; the proposed study aims to address this knowledge gap. The central hypothesis is that LF oscillations (~0.1 Hz) will improve CBF and tissue oxygenation under hypoxic and/or hypovolemic conditions, due to increased shear stress and the release of vasoactive mediators that facilitate vasodilation and enhanced tissue perfusion. This hypothesis will be addressed in two Specific Aims under hypoxic and hypovolemic conditions: 1) determine if inducing oscillations in arterial blood pressure and CBF at 0.1 Hz elicits shear stress-induced vasodilation, subsequently increasing CBF and oxygenation; and, 2) assess the effect of 0.1 Hz oscillations on the release of shear stress-induced vasoactive mediators. Twenty human subjects (males and females) will be recruited to address these aims using oscillatory lower body negative pressure (OLBNP) to induce 0.1 Hz oscillations. Measurements will include CBF (intracranial \& extracranial arteries), shear stress, cerebral oxygenation, arterial pressure, and venous blood samples for assessment of nitric oxide, prostaglandin E2, 6-keto-PGF1α (a metabolite of prostacyclin, PGI2), histamine, and endothelin-1. The rationale for the proposed research is to identify a mechanism for the previously observed increase in tolerance to simulated hemorrhage with increases in LF oscillations in arterial pressure and CBF. The approach is innovative as it challenges the traditional association of hemodynamic variability with negative clinical outcomes using a novel methodological approach in human subjects. This contribution is significant as the findings may provide an alternative approach to maintaining cerebral perfusion and oxygenation under conditions of hypovolemia and/or hypoxia.
- Conditions
- Hemorrhage
- Being tested
- 0 Hz Control, 0.1 Hz PPT, 0.05 Hz PPT
- Medical subject headings
- Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
0 Hz ControlOther
Lower body negative pressure (LBNP) applied to -60 mmHg for 10-min
0.1 Hz PPTOther
Lower body negative pressure (LBNP) applied at a frequency of 0.1 Hz from -30 mmHg to -90 mmHg
0.05 Hz PPTOther
Lower body negative pressure (LBNP) applied at a frequency of 0.05 Hz from -30 mmHg to -90 mmHg
| Study group | Role | What they receive |
|---|---|---|
| Pulsatile perfusion therapy (PPT) | Experimental | Application of oscillatory lower body negative pressure (LBNP) at specific target frequencies of interest. Receives: Other: 0 Hz Control; Other: 0.1 Hz PPT; Other: 0.05 Hz PPT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in ScO2
Cerebral tissue oxygen saturation
Measured: Up to 3-months
Change in ICA flow
Internal carotid artery blood flow
Measured: Up to 3-months
Change in MCA velocity
Middle cerebral artery velocity
Measured: Up to 3-months
Change in circulating vasoactive mediators
Venous plasma nitric oxide and endothelin
Measured: Up to 3-months
Secondary outcomes (5)
Change in arterial pressure
Systolic, diastolic, and mean arterial pressure
Measured: Up to 3-months
Change in heart rate
Heart rate
Measured: Up to 3-months
Change in stroke volume
Stroke volume
Measured: Up to 3-months
Change in PCA velocity
Posterior cerebral artery velocity
Measured: Up to 3-months
Change in etO2 and etCO2
End-tidal oxygen and carbon dioxide
Measured: Up to 3-months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2023
- Study start27 Feb 2020
- Primary completion17 Dec 2021
- Study completion17 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HemorrhageStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Caroline Rickards
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Caroline Rickards, University of North Texas Health Science Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05983744
- Sponsor's protocol ID
- IRB #2019-046
- Acronym
- PPT2
- Status last verified
- Aug 2023
- First submitted
- 23 Nov 2021
- Last updated
- 9 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD that underlie the results in a publication
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pulsatile Perfusion Therapy Phase II: A Novel Approach for Improving Cerebral Tissue Blood Flow and Oxygenation
- ClinicalTrials.gov ID
- NCT05983744
- Acronym / sponsor ID
- PPT2 / IRB #2019-046
- Conditions
- Hemorrhage
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Caroline RickardsUniversity, hospital or other
- Study start
- 27 Feb 2020 (actual)
- Primary completion
- 17 Dec 2021 (actual)
- Study completion
- 17 Dec 2021 (actual)
- First posted
- 9 Aug 2023 (actual)
- 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.
Individuals who suffer from a stroke, cardiac arrest, or traumatic bleeding (hemorrhage) injuries often have compromised blood flow and oxygen to the brain which can lead to the death of brain cells, and if the patient survives, subsequent difficulty in thinking and performing tasks of daily living. Traditionally, delivery of a constant flow of blood to the brain has been thought to be the most important factor for the survival of brain cells. In this study, a novel intervention will be assessed called "pulsatile perfusion therapy", delivering blood flow in a slow pulsing pattern. It is anticipated this intervention will improve brain blood flow and oxygenation during these serious clinical events.
There is a specific interest in whether delivery of brain blood flow with a slow pulsatile pattern will improve oxygenation of brain tissue, particularly when the brain is challenged under low oxygen (hypoxia) and low volume (hypovolemia) conditions, simulating stroke, cardiac arrest, and hemorrhage. A technique called oscillatory lower body negative pressure (OLBNP) will be used in healthy human participants, facilitating delivery of blood flow to the brain with different pulsing patterns. This technique will allow for determination of the ideal pattern of brain blood flow that improves oxygenation of the brain tissue. Measurements will be made of substances in the blood that may be released with pulsatile flow which act on the blood vessels to increase flow and delivery of oxygen.
Detailed description
Hemorrhage due to trauma is one of the leading causes of morbidity and mortality worldwide in both the civilian and military settings. A major factor contributing to death and disability from severe blood loss is poor tissue perfusion and oxygenation of the vital organs. Traditionally, protection of absolute cerebral blood flow (CBF) has been deemed the most important factor in maintaining perfusion and oxygenation. In recent years, it has been shown that low frequency (LF, ~0.1 Hz) pulsatile CBF is associated with increased tolerance to simulated hemorrhage in healthy human subjects, despite ≥30% reductions in absolute CBF. The underlying mechanism for this improvement in tolerance is unclear; the proposed study aims to address this knowledge gap. The central hypothesis is that LF oscillations (~0.1 Hz) will improve CBF and tissue oxygenation under hypoxic and/or hypovolemic conditions, due to increased shear stress and the release of vasoactive mediators that facilitate vasodilation and enhanced tissue perfusion. This hypothesis will be addressed in two Specific Aims under hypoxic and hypovolemic conditions: 1) determine if inducing oscillations in arterial blood pressure and CBF at 0.1 Hz elicits shear stress-induced vasodilation, subsequently increasing CBF and oxygenation; and, 2) assess the effect of 0.1 Hz oscillations on the release of shear stress-induced vasoactive mediators. Twenty human subjects (males and females) will be recruited to address these aims using oscillatory lower body negative pressure (OLBNP) to induce 0.1 Hz oscillations. Measurements will include CBF (intracranial \& extracranial arteries), shear stress, cerebral oxygenation, arterial pressure, and venous blood samples for assessment of nitric oxide, prostaglandin E2, 6-keto-PGF1α (a metabolite of prostacyclin, PGI2), histamine, and endothelin-1. The rationale for the proposed research is to identify a mechanism for the previously observed increase in tolerance to simulated hemorrhage with increases in LF oscillations in arterial pressure and CBF. The approach is innovative as it challenges the traditional association of hemodynamic variability with negative clinical outcomes using a novel methodological approach in human subjects. This contribution is significant as the findings may provide an alternative approach to maintaining cerebral perfusion and oxygenation under conditions of hypovolemia and/or hypoxia.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pulsatile perfusion therapy (PPT) | Experimental | Other: 0 Hz Control, Other: 0.1 Hz PPT, Other: 0.05 Hz PPTApplication of oscillatory lower body negative pressure (LBNP) at specific target frequencies of interest. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Aged 18 to 40 years
- Non-tobacco/nicotine users (e.g., cigarettes (including electronic cigarettes), chewing tobacco, nicotine gum or patches)
- Systolic arterial pressure <140 mmHg; diastolic arterial pressure <90 mmHg
- Normal 12-lead ECG (reviewed by a physician)
- Normal clinical results from a medical exam reviewed by a board certified physician (e.g., General Health Questionnaire - see attached document)
Key exclusion criteria (26 listed)
- Age <18 or >40 years
- Use of tobacco/nicotine within the last 6 months (e.g., cigarettes (including electronic cigarettes), chewing tobacco, nicotine gum or patches)
- Body mass index (BMI) >30 kg/m2 unless athletic/muscular build; calculation = body weight (kg)/height (m2)
- Not abstaining from the following 24 hours prior to the experimental session: exercise, alcoholic substances, prescription or non-prescription medications (unless cleared by the medical screener), dietary supplements, herbal medications, caffeinated substances (including coffee, tea (iced or hot), caffeinated energy drinks or sodas).
- Inability to visualize the internal carotid and vertebral arteries (via Doppler ultrasound) for accurate measurement of velocity and diameter.
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 |
|---|---|---|
| 0 Hz ControlLower body negative pressure (LBNP) applied to -60 mmHg for 10-min | Other | Pulsatile perfusion therapy (PPT) |
| 0.1 Hz PPTLower body negative pressure (LBNP) applied at a frequency of 0.1 Hz from -30 mmHg to -90 mmHg | Other | Pulsatile perfusion therapy (PPT) |
| 0.05 Hz PPTLower body negative pressure (LBNP) applied at a frequency of 0.05 Hz from -30 mmHg to -90 mmHg | Other | Pulsatile perfusion therapy (PPT) |
Primary outcome
Change in ScO2
Time frame: Up to 3-months
Cerebral tissue oxygen saturation
Change in ICA flow
Time frame: Up to 3-months
Internal carotid artery blood flow
Change in MCA velocity
Time frame: Up to 3-months
Middle cerebral artery velocity
Change in circulating vasoactive mediators
Time frame: Up to 3-months
Venous plasma nitric oxide and endothelin
5 secondary outcomes
Change in arterial pressure
Time frame: Up to 3-months
Change in heart rate
Time frame: Up to 3-months
Change in stroke volume
Time frame: Up to 3-months
Change in PCA velocity
Time frame: Up to 3-months
Change in etO2 and etCO2
Time frame: Up to 3-months
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 9 Aug 2023.
- Individual participant dataSharing planned: Yes. All IPD that underlie the results in a publication
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 0.1 Hz PPT and 0.05 Hz PPT in people with Hemorrhage, run by Caroline Rickards 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 8 inclusion and 26 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 9 Aug 2023. 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.
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.
What does the primary outcome measure?
Change in ScO2 (time frame: Up to 3-months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Aug 2023.