Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04954157 |
| Other study ID # |
IRB20-0898 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
June 29, 2020 |
| Est. completion date |
April 21, 2022 |
Study information
| Verified date |
November 2022 |
| Source |
University of Chicago |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The two-part phases will each have a unique patient population, The goal in this application
is to see if that carotid bodies are "offline" is correct and to determine whether a cohort
of SARS-Cov-2 patients can be identified who fit this profile and would be suitable for drug
treatment.
The testing will require one group of subjects to hold their breaths for a short period while
the investigators monitor vital signs and blood O2 levels. A second group of "healthier"
COVID subjects will be asked perform a walk-test inside their rooms for six minutes while
vital signs are monitored as well as blood O2 levels. If the subjects are in the healthy
control group, they will perform the walk test in a designated hallway at the medical center
also while there vitals are being monitored. The goal, using a mild stimulus, is to determine
whether respiration increases if blood O2 saturation is decreased. If it does not, that would
indicate a failure of the carotid body oxygen sensing system.
Description:
Many patients infected with SARS-CoV-2 are hypoxic (O2 blood saturation below 92%). Many do
not even realize they are hypoxic, since breathing can remain comfortable. In these patients,
the normal physiologic responses to low oxygen, increased respiration, appears to be absent
(Couzin-Frankel, 2020).
A wide variety of cell types within the body express the ACE2 receptor that is required by
the virus to infect cells. This included the cells of the carotid body, which are the O2
sensors of the body. The investigators hypothesize that glomus cells of the carotid body are
among the first cells infected due to their extremely high blood perfusion rates. After
infection, they are "offline" and the body no longer recognizes that it is hypoxic. This can
be extremely detrimental to patients that may require mechanical ventilation to re-establish
normal blood O2 levels (>95% saturation). Death rates on patients using mechanical
ventilators are very high and every effort should be made to keep patients off these
machines.
Interestingly, hypoxia appears to be a common condition in SARS-CoV-2 infected people, with
some showing serious respiratory conditions (acute respiratory distress syndrome - ARDS), but
others not. The majority appear to die from a "cytokine storm", a massive reaction to the
infection by the immune system (Xie et al., 2020). But many others are hypoxic and sick. Many
medical centers are treating SARS-Cov-2 patients identically, placing them on mechanical
respirators. Below is a short description from a German group from an editorial that was
recently published (Gattinoni et al., 2020) suggesting that not all SARS-CoV-2 hypoxic
patients are the same and so should not be treated identically.
It has been known for a long time that mechanical ventilation in ICU patients, not related to
SARS-CoV-2, can be very hard on patients with death rates above 50% (Fialkow et al., 2014)
and with very long recovery times (Griffiths & Jones, 1999). Patients admitted to ICUs who
need mechanical ventilation are expected to have higher mortality rates compared with those
who do not require respiratory support (Vincent et al., 2002) as a consequence of
ventilator-induced lung injury (VILI). Intubated patients infected with SARS-CoV-2 also have
very high death rates (Richardson et al., 2020). Undoubtedly, they are the sickest of the
sick. Nonetheless, everything possible should be done to prevent intubation a policy
consistent with University of Chicago usage of high flow nasal cannulation. The investigators
goal with this IRB submission is to identify a cohort of SARS-CoV-2 patients that are hypoxic
but their breathing is not responding correctly to the hypoxia ("silent hypoxia"). It is
possible that these patients can be treated with drugs, in order to keep them from intubation
for as long as possible.
Phase I - Study of silent hypoxia in SARS-CoV-2 infected patients. Phase 1 will recruit 40
subjects with documented SARS-CoV-2 infection and another 40 healthy subjects as the control
group. Totaling 80 subjects in the first phase. This large a group is not required to
determine if "silent hypoxia" exists, rather to determine the percentage of patients
exhibiting altered oxygen sensing, among this patient population.
This Phase will include observation and collection of clinical data that is routinely
captured in hospitalized COVID patients. All COVID-19 patients at the University of Chicago
Medical Center (UCMC) are connected to telemetry monitors that measure vital signs.
Peripheral oxygen saturation (SpO2), respiratory rate (RR), and heart rate (HR) are
continuously measured by the telemetry monitors. Blood pressure is intermittently checked and
measured by the telemetry monitor at an interval determined by physician orders at admission.
Prior to the subject's performing the test, they will have the option of watching a brief
instructional video, created by the PI, on how to correctly perform the phase one test. Both
the COVID and healthy subjects will have this option, if they feel they need further
instruction other than what the clinician administering the test has already provided. Once
the subject feels ready, will then be asked to hold their breaths up to 60 seconds or until
they can no longer hold their breath. Every patient will be asked to hold their breath 3
times with 5 minutes of rest between trials. Subjects will be instructed to hold their breath
and their vital signs will be recorded before, during, and after breath holding by the
patient's attending physician in the COVID unit. The goal is to see whether breath holding
makes the subject uncomfortable, as it would do in a normal subject. If their O2 sensing is
impaired the drive to breath may be absent or diminished. After the breath holding stops, it
is expected that the patient may start to gasp and breathe more rapidly, to make up for the
oxygen deficit. Will all subjects respond to hypoxia correctly? Or will some subjects ignore
the hypoxia, because they do not know they need to stop? In that case, a member of the study
team will stop them.
To ensure patient safety the attending physicians will instruct and monitor subjects while
they are participating in this study. Changes in O2 saturation below 85% or an absolute drop
of more than 8% will trigger the physician to instruct the patient to start breathing. Table
1, below, will guide breath-holding criteria.
Phase II - Studies of silent hypoxia in SARS-CoV-2 infected patients. Phase 2 will recruit 10
subjects and ask them ambulate for six minutes in their hospital room. This length of time is
adapted from the six minute walk test (6MWT), which is a well validated measure of both
aerobic and functional capacity (Troosters et al., 2002; Enright, 2003). The purpose of the
experiment is to test whether simple physical exertion in ambulatory COVID patients is
associated with reductions in SpO2 and/or physiologic changes in vital signs. The 6MWT will
be adapted and ask subjects to ambulate back and forth in their room (rather than along a
100m corridor), since this study is primarily interested in the physiologic responses to
exertion (rather than total distance walked). The study team will also measure at baseline
and after completion of walking a set of vital signs as well as ask subjects about their
perceived exertion using the Borg Rating of Perceived exertion instrument. In this phase,
patients will be instructed and continuously monitored by attending physicians working in the
COVID unit. The attending physicians will monitor these patients by standing outside of the
patient's room but in full view of the patient through the window and/or doorway in the COVID
unit.
For this phase, patients will be recruited with a documented AM-PAC score ≥19. The AM-PAC
score is documented daily by UCMC nurses in the nursing and therapy flow sheets within EPIC.
The score of ≥19 is used by both UCMC nurses and physical therapists to indicate patients'
functional independence. The daily AM-PAC scoring of patients by nurses at UCMC is required
and based on an adapted version of the Activity Measure for Post-Acute Care (AM-PAC)
instrument (Haley et al., 2004). This nursing requirement and the adapted AM-PAC scoring was
a joint UCMC nursing and physical therapy initiative, Project Walk, to better target patients
who may or may not need PT during their admission based on their functional mobility.
To ensure patient safety the attending physicians will instruct and monitor patients while
they are participating in this study. Changes in O2 saturation below 85% or an absolute drop
of more than 5% will trigger the physician to instruct the patient to start breathing.
What if all SARS-CoV-2 patients have impaired O2 sensing? This may not be out of the
question, since it appears that loss of smell and taste are reliable indicators of infection
(Menni et al.). In that case, the investigators population studies will indicate that
everyone is hypoxic when stressed.
Subject Identification, Recruitment & Payment All COVID subjects will be recruited and
enrolled from the COVID unit at the University of Chicago Medical Center (UCMC). The healthy
subjects will come from the faculty and staff from UCMC. To avoid any possible bias, healthy
volunteers will not have any relationship to this study prior or be under the supervision of
the investigators at the time they participate in this study. The healthy subjects will not
be hospitalized at the time they are recruited for this study. Subjects will not be
compensated for participating in the study.
