Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT02447731 |
| Other study ID # |
Sound Energy |
| Secondary ID |
|
| Status |
Withdrawn |
| Phase |
N/A
|
| First received |
February 2, 2015 |
| Last updated |
May 1, 2017 |
| Start date |
July 2016 |
| Est. completion date |
June 2017 |
Study information
| Verified date |
May 2017 |
| Source |
Loma Linda University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Study of the effects of sonic pressure oscillations on pulmonary gas exchange with added
dead space.
Description:
Sound waves are used in various industries to accelerate the process of mixing or separating
fluids (gases/liquids). We have proved that certain sound waves can safely improve gas
exchange in the lung of rats through accelerating gas diffusion inside their airways and
alveoli. Now we want to see if similar sound waves can improve gas exchange in humans.
The device which creates the sound waves is a sonic pressure oscillator capable of making
sound waves similar in loudness and frequency to loud human singing or screaming. These
waves are mainly in the frequency range of 50-500 Hz (Hertz, oscillations per second) with
intensity of 85-105 dBs (deci Bells, unit of sound pressure intensity).
We performed two bench top studies and witnessed the ability of sound waves to augment gas
diffusion. In a pilot study in rats we showed a safe and significant improvement in
pulmonary gas exchange under influence of sound energy. The effects of sound waves on gas
exchange in a human subject, the principle investigator (PI), was also analyzed in a
metabolic test with promising results. A clinically significant improvement in the PI's
pulmonary gas diffusion was also noted in a DLCO (diffusing lung capacity for carbon
monoxide) test. On yet another test, artificially enlarged pulmonary dead space study, the
PI's transcutaneous oxygen and carbon dioxide pressures (PtcCO2 & PtcO2) were measured and
results were indicative of presence of desired and safe effects of particular sound waves in
pulmonary gas exchange. The above mentioned studies support the rationale, objectives, and
methodology of the proposed studies.
Our human studies will be composed of a primary and a secondary part. In the primary part,
the sound waves are not introduced into the subjects' lungs directly and they are rather
delivered into an open end cylinder while the subjects breathe the air from the closed end
of the cylinder. The sound intensity will be kept in the range of 95-105dB.
In the second part of the studies, the sound waves of lower intensity (85-95dB) are directly
introduced into the subjects' lungs while the subjects are going through 1) a metabolic test
and 2) a lung diffusion capacity (DLCO) test. The results of these tests will be compared to
the subject's baseline test results (without sound waves).
In both parts of the study, the subjects' nostrils will be clamped by ordinary plastic nose
clamps as they will be asked to hold a mouthpiece and breathe through it.
In the primary part, sound waves of 95-105dB will be delivered into a 16 L (liter) frustum
(conical cylinder). The frustum's wider base is open to room air but its smaller base is
closed. A 2x20 cm tube will connect the closed end of the frustum to the mouthpiece. The
subjects will be breathing in and out of the narrower (closed) base of the frustum through
the mouthpiece for 3 minute cycles followed by 3 minute cycles of breathing fresh room air.
The subjects' PtcCO2 and PtcO2 will be measured with the frustum held in various spatial
orientations in regard to its open base which will be 1) vertical upward (+90 degrees with
horizon), 2) horizontal (0 degrees), vertical downward (-90 degrees), and tilted to -45
degree angles. This test will take at least 6x4=24 minutes, and not more than 30 minutes for
each subject. Then same tests will be done with sound energy introduced into the frustum.
Total time for studying each subject will be approximately 48-60 minutes.
Secondary part of the study is composed of two sections. In the first section, diffusion
capacity of the lungs will be measure while the sound waves are being played by the
transducer and delivered via a mouth piece into the subjects' oral cavity. The sound waves
will be travelling down the pulmonary airways and into the alveoli. An examiner will listen
to the chest wall to make sure that the subject is allowing the waves to travel down the
airways without obstructing the path to the sound waves by inadvertently holding the tongue
up or holding breath. Said mouth piece is connected via a Y-connector to the DLCO machine
and the tube which delivers the sound waves. The duration of exerted sound effect will be
only 9 seconds as per protocol of a routine DLCO testing. This period coincides with the
time when the subject is taking a deep breath and holding it for 9 seconds. Lung diffusion
capacity of the subjects will be measured and compared with soundless test results. Although
the test uses very small amount of carbon monoxide (CO) as the tracer gas but the amount is
considered negligible and quite safe. This test has been done in humans routinely for many
years with no known discernible side effects. It has been approved by FDA many years ago.
There is an abundance of medical literature regarding the safety and methods used in DLCO.
There are also multiple YouTube videos showing how DLCO is done. We will encourage the
participants to watch these videos before the studies. The subjects will be sitting
comfortably on a chair and holding the mouth piece in their mouths and breathing the room
air. They can easily interrupt the test at any time by simply taking the mouthpiece out of
their mouths.
In the second section, subjects will go under metabolic tests where their exhaled oxygen
(O2) and carbon dioxide (CO2) are measured with and without sound effects. Metabolic tests
have been approved by FDA for many years and are generally considered very safe. During the
test, the participants breathe from the mouth piece with their nostrils clamped. Breathing
gases will be provided by connecting the mouth piece to a tube which usually has a base flow
of room air 40L/min or more. In order to show oxygenation improvement via sound energy we
will have to create a suboptimal respiratory environment and artificially induced hypoxia.
Mild hypoxia is generally well tolerated by healthy humans although it might make the
individual feel short of breath and tachypneic. We will add nitrogen to the supplied air to
bring the fraction of inhaled oxygen (FiO2) down to 17.5% which correlates breathing at an
altitude of 7500 feet (approximately 2250m), or similar to a ski resort, except that we
don't ask our subjects to get involved in vigorous exercise like skiing, and the test is
only ~20 minutes. The lowered FiO2 will bring the subjects' pulse ox (SpO2) down to 92-94%
which is generally considered safe and well tolerated by all normal human subjects with no
cardiopulmonary conditions. The resultant mild and transient respiratory alkalosis has no
clinical significance as it only involves a 20 minute test and the pH imbalance would be
buffered naturally without inducing any electrolyte abnormalities.
The acoustic transducer, as mentioned briefly earlier, is a simple sound wave generator and
is composed of a tone generator (usually a computer), an electronic amplifier, an acoustic
transducer similar to an ordinary loudspeaker, and a funnel and tubing system that directs
the sound waves into the subjects' mouthpiece. Its function is very similar to standing in
front of a loudspeaker and letting the sounds penetrate into the mouth/nose and down the
pulmonary airways except that in order to protect the ears and intensify the sounds a funnel
is used to capture the waves and direct them into the oral cavity via a tube. The device is
made, tuned, and calibrated by the principal investigator. It can produce tones from 20 Hz
to about 11 KHz with useful intensities ranging from 65dB to a maximum of 110dB. The simple
device has been successfully used in rats and a human (PI) without any discernible side
effects.
For more detailed description of the methodology and results of our previous studies please
refer to the attached documents with the referenced literature.
Data Collection:
During the first part of the study, data with subjects' PtcCO2, PtcO2, heart rate,
respiratory rate, minute volume, and blood pressure will be logged onto a spread sheet and
saved on password protected computers.
Lung diffusion capacity variations under the influence of sound vibrations will be measured
and recorded using a DLCO machine at the respiratory department of LLUMC. Data will also be
saved on password protected computers using encrypted MS-Excel in addition to the memory of
the DLCO machine. During the metabolic tests, inhaled and exhaled concentrations of O2 and
CO2 will be continuously monitored along with subjects' heart rate, breath rate, pulse
oxymetry, blood pressure, general comfort level of the subject and his/her clinical well
being. The encrypted and password protected data will be collected on Microsoft Spreadsheets
for statistical analysis by a biostatistician.
RISK AND INJURY:
Human ears are particularly prone to damage by loud sounds. Ear pain or discomfort can
happen at sound levels as low as 110dB but painful sound levels are generally considered to
be in the range of 125-135dB. Other organs tolerate sound wave much better and tissue damage
normally does not occur in sound intensity levels less than 160-170dB. Sound intensity will
be monitored and recorded during the studies. The intensities will always be kept to below
105dB which is significantly below any harmful levels considering the fact that sound
pressure levels are measure in logarithmic scale.
During the metabolic tests, the subjects pulse oximetry will be kept above 92% to avoid any
ill effects. These levels are very well tolerated by humans and ordinarily physicians do not
supplement any oxygen to patients at these levels. Very brief hypoxia with hypercapnia will
happen during the frustum test when the frustum is held at held at +90 degree position as
the SpO2 will plummet to upper 70s to lower 90s in about 3 minutes which is the limit of
this test. We will halt the test before the 3 min landmark if a subject's SpO2 went below
80%. The brief and transient hypoxia and hypercapnia is well tolerated. A medical doctor
will be present at all times whenever the tests are running. A thorough medical exam
immediately before the tests will secure safety of the subjects as well.
Metabolic studies and DLCO tests have been done routinely for many years/decades and are
generally considered very safe. The amount of inhaled carbon monoxide used as a tracer gas
in DLCO is significantly below any toxic levels. These tests have been approved by FDA for a
long time and are considered safe even in patients with pulmonary disorders.
BENEFITS:
The studies do not have any direct or immediate benefit to the subjects participating in the
study. It has been anticipated that sound waves may help decrease incidence and severity of
"ventilation induced lung injury or VILI" to an extent yet to be measured. The main reason
behind this postulation is that addition of proper sound waves to breathing gases will
enable us to effectively ventilate lungs with lower FiO2 and/or less mean airway pressure
(Pmaw) compared to the currently available technologies. It is known for a long time that
high FiO2/Pmaw are the two major predictors of VILI. It is also anticipated that the outcome
of cardiopulmonary resuscitation (CPR) and many acute or chronic pulmonary disorders such as
COPD, asthma, cystic fibrosis, bronchopulmonary dysplasia, restrictive lung disorders, acute
lung injury, pneumothorax, RDS, and some other conditions may improve through use of proper
sound waves.
