A Pilot Study to Assess Transmembrane Electromyography (TM-EMG) for the Assessment of Neuromuscular Function in the Oropharynx
Phase: NA
Conditions: Obstructive Sleep Apnea, Amyotrophic Lateral Sclerosis, Muscular Dystrophies, Healthy
Sponsor: Powell Mansfield Inc.

Transmembrane Electromyography (TM-EMG) for the 
Assessment of Neuromuscular Function in the Oropharynx 
 
Principal Investigator: Perry Mansfield, M.D. 
Co-Principal Investigator: Vera Bril, M.D. 
Subinvestigator: Michael O’Leary, M.D. 
 
Sponsor: Powell Mansfield, Inc. 
Funded by: Powell Mansfield, Inc. 
 
Version 2 
April 4, 2019 
 
 
 

 
 
STUDY SUMMARY 
Study Description: 
Transmembrane electromyography (TM-EMG) may be a feasible and 
valid non-invasive EMG technique for detecting neuromuscular (NM) 
impairment. This study will assess whether, in healthy volunteers and 
participants with known obstructive sleep apnea (OSA) and other NM 
diseases involving the oropharynx, the same characteristic motor unit 
potentials obtained on conventional needle EMG (NEMG) can be 
obtained using a TM-EMG sensor. The purpose of this study is to 
demonstrate whether the TM-EMG sensor can provide the 
same diagnostic accuracy as the concentric needle electrode for the 
diagnosis of NM diseases. Having demonstrated diagnostic similarity of 
TM-EMG to NEMG, the secondary aim of this study is to confirm that 
NM disturbance of oropharyngeal striated muscles in participants with 
OSA can be elicited with the TM-EMG sensor. 
 
Objectives: 
 
Primary Objective: To validate the TM-EMG sensor as a non-invasive 
technique for the assessment of neuromuscular function in the 
oropharynx. 
Secondary Objective: To elicit, using the TM-EMG sensor, 
neuromuscular findings that correlate to OSA in affected participants. 
Endpoints: 
Primary Endpoint: Proof of diagnostic consistency using both the TM-
EMG sensor and NEMG in neuromuscular disorders affecting 
oropharyngeal muscles.  
Secondary Endpoint: Proof that participants with known OSA exhibit 
EMG findings different from healthy participants and that these 
findings can be detected using both the NEMG and the TM-EMG 
sensor. 
 
Study Population: 
 15 total participants with disorders affecting the function of 
oropharyngeal muscles 
• 10 participants with one of the following neuromuscular 
disorders: 

- ALS with the presence of bulbar symptoms  
- muscular dystrophy with the presence of bulbar 
symptoms 
• 5 participants with severe OSA 
 8 healthy volunteer participants 
 
Phase: 
Pilot 
 
Description of 
Sites/Facilities 
Enrolling 
Participants: 
All study recruitment and screening will occur at the SENTA Clinic in 
San Diego, CA, USA; a tertiary referral center which focuses on diseases 
of the head, neck, brain and spine. All EMG testing procedures will be 
performed in this clinic under the supervision of an expert 
otolaryngologist who will obtain the EMG tracings. In-Laboratory 
polysomnogram (PSG) studies, if required, will be performed at 
AmeriSleep Diagnostics in San Diego, CA, USA; a comprehensive and 
ACHC accredited sleep diagnostic facility. 
 
Description of 
Study Intervention: 
Medical device for use as novel diagnostic modality. 
Examination of the electromyographic signal from oropharyngeal 
muscles obtained using an investigational TM-EMG sensor attached to 
a rigid probe and a very fine concentric needle electrode (Ambu 
Neuroline 25 mm x 30G). 
 
Study Duration: 
Six months 
 
Participant 
Duration: 
• 60 minutes for in-office screening exam. 
• 60 minutes for in-office EMG exam.  
• Healthy participants: One overnight stay for In-Laboratory 
Polysomnogram (PSG).  
 
  

STUDY BACKGROUND AND RATIONALE 
Electromyography (EMG) is the electrophysiological examination of muscle used for the 
diagnosis of suspected neuromuscular (NM) disorders such as myopathies, neuropathies, 
neuronopathies and neuromuscular junction disorders. 1 Routine needle electromyography 
studies (NEMG) are mainly restricted to skeletal limb muscles, which are easily accessible, and 
are not performed routinely on less accessible muscles, such as striated muscles of the 
oropharynx. This limits the evaluation of neuromuscular involvement in disorders involving 
muscles of the oropharynx such as obstructive sleep apnea (OSA) and neurogenic 
oropharyngeal dysphagia. Surface EMG (SEMG) is a non-invasive EMG method that assesses 
muscle function by recording muscle activity from one or more electrodes placed on the 
surface of the skin above the muscle or muscles to be examined but lacks the signal quality to 
provide diagnostic information on individual motor unit morphology and recruitment. 2,3 
In-laboratory polysomnography (PSG) is considered the gold standard for diagnosis of OSA. 4 
This study measures numerous sleep metrics including oxygen level, sleep stages, REM 
patterns, wakefulness, EKG, and leg movements. An apneic event is defined by a 4% drop in the 
level of oxygen associated with a pause in breathing of 10 seconds or longer.  The diagnosis of 
OSA is determined by the apnea/hypopnea index (AHI) [normal ≤ 5, mild OSA 5-15, moderate 
15-30 and severe OSA  > 30]. 5 
A videofluoroscopic swallowing evaluation (VFSE) is currently considered the diagnostic gold 
standard for accurate assessment of oropharyngeal dysphagia arising from pharyngeal muscle 
dysfunction due to multiple etiologies including neurologic disorders such as stroke, Parkinson’s 
disease (PD), multiple sclerosis (MS), multi-system atrophy (MSA), and amyotrophic lateral 
sclerosis (ALS); autoimmune disorders such as myasthenia gravis; and myopathies such as 
muscular dystrophy. Both PSG and VFSE are laborious, costly, and have limited accessibility for 
the diagnosis of muscular disorders of the oropharynx. 
Our body contains more than 600 skeletal muscles as well as cardiac and smooth muscles with 
different properties and different selective vulnerability for certain disease processes, owing to 
structural or physiological differences. Disease processes that affect the limb muscles differ 
from those affecting cardiac, gastrointestinal, or urogenital muscles. From a practical and 
clinical point of view, it is essential in most clinical scenarios to be able to confirm and 
characterize the nature of muscle disease, to provide appropriate and effective treatment. 
OSA is a collective term used for conditions that over time cause damage to the delicate soft 
tissues of the upper airway from turbulent air flow and can comprise anatomically obstructive 
processes that result in nocturnal narrowing of the upper airway leading to partial or complete 
obstruction of the airway. The upper airway encompasses the entire upper airway passages 
to include the nasal cavity, oropharynx and hypo-pharynx. Partial and total airway obstruction 
results in sleep arousals, sleep fragmentation and subsequent behavioral derangements 
such as excessive daytime sleepiness. Concurrently, pathophysiologic derangements usually 

accompany the behavioral decrements with altered daytime performance and excessive 
daytime sleepiness. The cardiovascular derangements can cause in part high blood pressure, 
stroke, myocardial infarction and death. Decreased quality of life and a shortened life span 
are common in participants with untreated OSA. 
Although the complications of OSA are well known, the physiological mechanism for upper 
airway collapse during inspiration and sleep is not clear. Nonetheless, there is substantial 
physiological, electrophysiological and histological evidence for neuromuscular impairment in 
the upper airway in participants with OSA, 2 6 and pharyngeal nerve injury has been proposed as 
a possible contributory factor in OSA development, 2 which might be related to vibratory 
trauma caused by sleep-disordered breathing. 7 Evidence for sensory involvement in 
participants with OSA includes the finding of abnormal two-point palatal sensory 
discrimination, 8 and disordered thresholds for warmth and cold detection in the oropharyngeal 
mucosa. 9 Although the activity of the genioglossus, an upper airway dilator muscle, was found 
to be significantly greater during wakefulness in OSA, possibly due to a reflex-driven 
neuromuscular compensation for an anatomically compromised airway, a greater decline was 
observed during the early and late sleep onset period, suggesting the loss of this reflex. 10 
Evidence for motor nerve fiber loss was shown by needle electromyography (EMG), 
demonstrating longer duration motor unit potentials (MUP) with larger size index. 2 Histological 
evidence for neuromuscular impairment in the upper airways includes frequent focal 
degeneration of myelinated nerve fibers and axons,9 increased number of sensory and motor 
nerve fibers, indicating peripheral sprouting secondary to neuropathy, 11 abnormal muscle fiber 
variability with increased amount of connective tissue, and alternation in myosin heavy chain 
compositions. 12,13 
Dysphagia is difficulty swallowing due to structural or functional impairment of the 
aerodigestive tract. Such impairment may arise from an underlying neurological disorder 
producing oropharyngeal dysphagia (OPD). Participants with OPD have difficulty initiating 
swallowing and present with choking, nasal regurgitation or coughing episodes while eating, 
and drooling due to difficulty managing saliva. In addition, neurogenic OPD may be complicated 
by aspiration pneumonia, dehydration and malnutrition, increasing the morbidity of the 
underlying neurological disorder. Participants with symptoms of oropharyngeal dysphagia 
undergo a VFSE, which in the case of neurogenic OPD, typically reveals impairment of 
oropharyngeal motor performance and/or laryngeal protection. 14  
Electrophysiologic examination of muscles can provide diagnostic information as to the 
underlying process: myopathy, neuropathy, neuronopathy or neuromuscular junction 
disorders.  There are currently two primary types of EMG techniques or methods: intramuscular 
or needle EMG (NEMG) and surface EMG (SEMG). NEMG involves the insertion of a needle 
electrode directly into the muscle to be examined and is considered the gold standard for 
assessing the muscle attributes of neuromuscular diseases. NEMG allows the clinician the 
ability to provide a precise evaluation of key indicators of neuromuscular function such as 

spontaneous activity and motor unit action potential (MUAP) recruitment and morphology. 
These indices are utilized to: 1) differentiate between primary muscle pathology and muscle 
dysfunction secondary to nerve injury 2) characterize the nature of the pathology by the 
assessment of denervation activity which is typically indicative of an active disease process 3) 
assess re-innervation changes indicating disease chronicity and 4) define the topographical 
distribution of the neuromuscular disorder. 1 
However, NEMG is invasive and painful. Insertion of the needle damages the pierced tissues 
causing swelling and bleeding and nociceptor activation causes pain. There is risk of infection, 
viscus perforation and disease transmission. 3 These drawbacks are especially evident in areas 
of the body that are sensitive or dangerous places to use a needle such as the mouth/pharynx, 
eyes, ears, GI tract, urinary system, and myocardium. Consequently, NEMG is not used in these 
areas routinely in EMG laboratories. In an awake participant, needle electrode placement into 
oral or pharyngeal muscles is constrained by the gag reflex, insertion pain, procedure fear, local 
trauma, and bleeding risk. Once inserted, the needle electrode must be optimally positioned to 
record muscle activity. This requires repositioning of the needle in the muscle which further 
challenges participant tolerance and compliance.  
SEMG is a non-invasive EMG method that assesses muscle function by recording muscle activity 
from one or more electrodes placed on the surface of the skin above the muscle or muscles to 
be examined. The main advantages associated with SEMG are that it is a pain-free technique 
which is not associated with the bleeding and infection risks of NEMG. As a result, SEMG can be 
used to record signals from many sites and motor units at the same time, for prolonged periods 
of time, and during activity. An additional potential advantage, is a larger recording area, 
making possible the collection of data over a wider region of muscle.5 Due to these attributes, 
SEMG is used routinely for obstetric monitoring, kinesiologic analysis of movement disorders 
and in rehabilitation.3 However, the role of SEMG in the diagnosis of neuromuscular disorders is 
limited by lack of information on insertional activity, spontaneous activity, motor unit size and 
shape, and interference pattern. In fact, the American Academy of Neurology concluded that 
SEMG is substantially inferior to NEMG for the evaluation of participants with neuromuscular 
disorders. Furthermore, SEMG has limited spatial resolution, is more susceptible to mechanical 
and electrical artifact, and is more likely to show cross-talk between adjacent muscles than 
NEMG. 3 Finally, SEMG uses adhesive surface electrodes that are not appropriate for muscles 
located within internal body cavities and organ systems with moist mucous membranes. 
Development of surface sensors and probes for internal use has not been successful so far. 
Electrophysiological examination of the muscles located in body cavities such as the oropharynx 
could provide physicians with valuable data to aid in diagnosis and treatment. For example, 
pharyngeal muscles located in the oropharynx that act to dilate the airway do not function 
properly in participants with OSA. These muscles can also be affected in gastrointestinal 
conditions such as dysphagia, which may involve dysfunction of pharyngeal muscles. 

Due to the drawbacks and limitations of both NEMG and SEMG, routine clinical EMG 
examination of these types of muscles is not feasible or practical. Therefore, there is a need to 
provide an EMG sensor that can overcome the drawbacks of NEMG and the deficiencies of 
SEMG to provide accurate diagnostic data for the clinical evaluation of participants with 
neuromuscular disorders affecting muscles located in body cavities or associated with internal 
organ systems. 
For that reason, we propose a pilot study to examine the diagnostic utility of a novel 
transmembrane surface sensor, and compare signals obtained with the TM-EMG sensor to 
conventional NEMG signals participants from healthy volunteers to those with documented 
neurologic pharyngeal muscle dysfunction (ALS and muscular dystrophy) and to those with 
severe OSA. 
 
STUDY SETTING 
Study recruitment will occur at the SENTA Clinic in San Diego, CA, USA; a tertiary referral center 
which focuses on diseases of the head, neck, brain and spine. All EMG testing procedures will 
be performed in this clinic under the supervision of an expert otolaryngologist who will obtain 
the EMG tracings. In-Laboratory polysomnogram (PSG) studies will be performed at AmeriSleep 
Diagnostics in San Diego, CA, USA; a comprehensive and ACHC accredited sleep diagnostic 
facility. 
 
STUDY DESIGN 
This is a prospective, cohort, pilot study of adults from healthy volunteers to those with 
documented neurologic pharyngeal muscle dysfunction (ALS and muscular dystrophy) and to 
those with severe OSA; assessing diagnostic properties of EMG studies using a conventional 
needle and TM-EMG sensor in pharyngeal muscles. 
OBJECTIVES and HYPOTHESIS 
Primary Objective 
To validate the TM-EMG sensor as a non-invasive technique for the assessment of 
neuromuscular function in the upper airway.  
Secondary Objective 
To elicit, using the TM-EMG sensor, neuromuscular findings that correlate to OSA in affected 
participants. 
Study Hypothesis 

The primary hypothesis is that transmembrane EMG (TM-EMG) examination of muscles located 
within internal body cavities and organ systems such as the oropharynx using the TM-EMG 
sensor will have similar diagnostic findings to the conventional NEMG examinations and that 
neurogenic changes will be observed in OSA.  
Eligibility Criteria 
Inclusion Criteria 
• 
Gender: Male and or female 
• 
Age: 18-70 years 
• 
Must be able pause use of anticoagulation, NSAID and multi-vitamins for appropriate period prior to 
study test. Timeline and safety to be determined by principal investigator.  
• 
A cohort of participants with documented neurological disorders involving upper airway striated 
muscles including ALS and muscular dystrophy with the presence of bulbar symptoms.  
• 
A cohort of participants diagnosed with moderate to severe OSA on in-lab PSG, including the 
following criteria: 
o AHI > 25 made up of primarily of obstructive apneas and hypopneas. 
o Nadir Sa02 < 85% 
o Untreated 
• 
A cohort of healthy participants that meet the following criteria  
o Normal craniofacial anatomy 
o AHI ≤ 2 
o Epworth score ≤ 10 
o Stop-Bang score ≤ 2 
o BMI < 30 
Exclusion Criteria 
• 
Allergy to topical anesthetic agent.  
• 
Heavy alcohol use – defined as 4 or more alcoholic drinks on the same occasion on 5 or more days in 
the past month.  
• 
Any type of smoking with 10 days prior testing. 
• 
The presence of any underlying medical, surgical or psychiatric disorder that would preclude 
participation in the study as determined study principle investigators. 

• 
 Prior radiation to the oral cavity. 
• 
Craniofacial anatomical disorders. 
Interventions (Diagnostic Procedure) 
EMG Testing Procedure 
Study participants will be seen by Dr. Mansfield in an outpatient otolaryngology clinic in San 
Diego, California (SENTA Clinic). Drs. O’Leary and Bril will serve as consulting physicians. All 
participants will be evaluated and selected as study candidates based on inclusion/exclusion 
criteria. 
Baseline data obtained will include participant demographic information, a comprehensive 
history including HPI, medications, past medical history, allergies, family history, social history—
including smoking and alcohol consumption, STOP-Bang, and Epworth sleepiness scale. A 
comprehensive physical examination will be performed. The data will be documented using 
Cerner Ambulatory Electronic Health Record. Once a candidate is selected for the trial, they will 
be presented with the risks and benefits of this study. This will be discussed with each 
participant prior to written consent being obtained. Risks include induction of a gag reflex 
and/or feeling of nausea, minor irritation or bleeding at the testing site, mild allergic reactions 
to the topical anesthetic or to the probe tip itself, infection at the needle insertion site. All 
reactions, if any, are expected to be minor. 
Standard ENT examining room equipment and supplies will be available as part of the study.  
The participant will be positioned in a powered reclining and elevating otolaryngology 
examination chair. The testing physician will stand to the left of the sitting participant, and the 
participant will be positioned at the appropriate height, head supported in a headrest, to allow 
the physician to adequately visualize the soft palate anatomy. The physician will use a headlight 
to illuminate the oral airway. Photographs of the participant and the participant’s soft 
palate/tongue/dentition and oral airway will be taken, and anatomic findings documented. 
Participant’s blood pressure, heart rate, and respiratory rate will be recorded prior to the start 
of testing. 
The skin of the cheek on the zygomatic arch will be prepared and cleaned with an alcohol swab 
to optimize skin contact with the ground electrode. The investigational TM-EMG probe device is 
hooked up to the EMG system.  
The participant will open his or her mouth adequately to allow for visualization of the soft 
palate musculature by the physician. For participants in which the palatopharyngeus/ 
palatoglossus or musculus uvulae are poorly seen, gentle tongue depression will be used to 
better visualize the anatomy.  

Topical 20% Benzocaine will be applied to the mucosal surfaces overlying the muscles to be 
examined using the TM-EMG probe prior to the start of testing. With the participant’s mouth 
open and in neutral position, the TM-EMG probe is positioned on the mucosal surface 
correlating to the expected midpoint of the palatoglossus by the co-investigator. Free run EMG 
recording of the palatoglossus will be obtained. Once an optimal EMG tracing is obtained the 
probe will be released off the mucosal surface. The same procedure is repeated on the 
contralateral palatoglossus.  
The same protocol will be used to test the genioglossus. The TM-EMG probe is placed on the 
mucosa of the genioglossus until an optimal EMG tracing is obtained. The same procedure is 
repeated on the contralateral genioglossus.  
The principal investigator will then take his turn at assessing the same muscles. The 
palatoglossus will be examined in the same location using the same TM-EMG probe. Once an 
optimal EMG recording is obtained, the TM-EMG probe will be released off the mucosal surface 
and a very fine concentric needle electrode (Ambu Neuroline 25 mm x 30G) will be placed into 
the palatoglossus using the procedure as described below. Needle insertion will be done in a 
straight line through the mucosal membrane into the midpoint of the muscle at the desired 
depth. 1-3 needle insertions will be used to obtain a diagnostic-quality EMG tracing from each 
muscle. The needle is placed in the same location tested by the TM-EMG probe. Once both 
tracings are recorded, the contralateral palatoglossus will be tested via both TM-EMG and 
NEMG. The principal investigator will then obtain bilateral genioglossus EMG using the same 
protocol that was used for the palatoglossus. 
The principal investigator will also obtain EMG data from both left and right palatopharyngeus 
using the TM-EMG probe and associated protocol. However, due to anticipated difficulty with 
gag reflex associated with the palatopharyngeus, NEMG will not be used at this site, and testing 
of this muscle will only be performed by the principal investigator. In total, 6 muscles locations 
will be tested via TM-EMG, and 4 muscle locations by NEMG.  
The free-run EMG tracing for both TM-EMG and NEMG will be displayed on an oscilloscope and 
heard through an audio-amplifier. All EMG recordings will be made using standard gain and 
sweep speed settings. Waveforms for both TM-EMG and NEMG tests will be recorded on a 
Cadwell Sierra Summit EMG system. 
We anticipate the recording time per muscle will be approximately 10 seconds. If participant 
exhibits intolerance during an individual muscle test, that particular muscle test will be 
discontinued. 
The participant will be examined at the conclusion of the EMG procedures for excessive 
bleeding or swelling. The participant will have blood pressure, heart rate, and respiratory rate 
checked for stability immediately upon completion of testing and prior to discharge. The 
participant will be given written instructions on how to contact the research staff should any 
adverse events arise, such as a sore throat, fever, testing site irritation or any other study 

related concerns. The research staff will contact the participant 1 day and 7 days after 
completion of the EMG test to document any adverse events the participant may have had 
following the testing. Responses will be documented in the EMR and serious adverse events will 
be reported to the study sponsor and IRB within 24 hours. Adverse events which occur more 
than 5 days after the EMG test will not be considered related to the study intervention, unless 
the investigator suspects a potential link. 
Sleep Study 
All healthy study participants selected for the study will be required to complete an overnight 
stay for an in-laboratory Polysomnogram (“PSG”).  
Study Endpoints 
TM-EMG and NEMG data will be analyzed offline upon completion of testing by Dr. Vera Bril. 
Analysis will include the presence of spontaneous activity (fibrillation potentials and positive 
sharp waves), MUP morphology (number phases, duration and amplitude) and recruitment 
pattern. MUP morphology will be analyzed manually. Each recording will be labeled as a normal 
or abnormal study. Abnormal studies will be classified into active or chronic neurogenic 
changes or myopathic changes. 
Secondary Endpoint 
Proof that participants with known OSA exhibit EMG findings different from healthy 
participants and that these findings can be detected using both the needle electrode and the 
transmembrane sensor.  
Analysis results will be compared between the healthy cohort and the neurologic disorders 
cohort; and between the healthy cohort and the OSA cohort. 
Sample Size Calculation 
Given that this is a novel EMG testing technique, a formal sample size calculation was not 
performed. The sample size chosen for this study was based on what would be reasonably 
feasible given constraints in areas such as funding and recruiting. The results from this pilot 
study will enable design of a larger, multi-site study adequately powered to show the diagnostic 
usefulness of TM-EMG. 
Statistical Methods 
Primary Endpoint 
Proof of diagnostic consistency using both the TM-EMG sensor and NEMG in neuromuscular 
disorders of the oropharyngeal muscles. 

All data will be examined to determine if there are any missing or non-plausible values, and 
these will be removed. Summary statistics will be calculated, including means or medians, 
minimums and maximums, standard deviations, and interquartile ranges.   
The distribution of EMG findings in OSA will be presented as descriptive statistics.  
 
ADVERSE EVENT MONITORING 
Documented above under Interventions. 
 
STUDY DISCONTINUATION 
Participants will be withdrawn from the study if they withdraw consent or if the study physician 
determines that there is a safety risk associated with their participation. If a participant exhibits 
intolerance during an individual muscle test, that particular muscle test will be discontinued. 
 
ANCILLARY OR POST-TRIAL CARE 
Following the trial, each participant will return to the clinical care of their original physician. We 
will also assume responsibility for any adverse effects or harms caused by the intervention. 
 
ETHICS AND DISSEMINATION 
Research Ethics Approval, Protocol Amendments, and Consent 
Participants who are eligible for study participation will be approached by the research 
assistants, to avoid any coercion on the part of the investigators.  Consent will be obtained in 
writing, with the risks and potential benefits of the study clearly explained in basic language in 
the consent form.   The participant will be allowed ample time to review the consent form prior 
to signing; and if the participant wishes to discuss the study with family members prior to going 
forward, they may take the consent form home.  The research assistants will be available to 
answer any questions about the study; and if the research assistants are unable to answer the 
question, this will be addressed by the study investigator.  All participants will be re-assured 
that at any point during the study, they may withdraw consent and end their participation in 
the study.  If consent is withdrawn, all data collected to that point remains as part of the study, 
however, will be de-identified. 
The study will be conducted in accordance with International Conference on Harmonisation 
Good Clinical Practice (ICH GCP), applicable United States (US) Code of Federal Regulations 

(CFR). The Principal Investigator will assure that no deviation from, or changes to the protocol 
will take place without prior agreement from the sponsor and documented approval from the 
Institutional Review Board (IRB), except where necessary to eliminate an immediate hazard(s) 
to the trial participants. The protocol, informed consent form(s), recruitment materials, and all 
participant materials will be submitted to the IRB for review and approval.  Approval of both 
the protocol and the consent form must be obtained before any participant is enrolled.  Any 
amendment to the protocol will require review and approval by the IRB before the changes are 
implemented to the study.  All changes to the consent form will be IRB approved; a 
determination will be made regarding whether a new consent needs to be obtained from 
participants who provided consent, using a previously approved consent form. 
Confidentiality, Data Access, and Declaration of Interests 
Participant confidentiality will be strictly maintained throughout the study.  All study records 
will be de-identified to maximum capability, and all study charts will be kept under lock-and-key 
in a secure office.  The study charts will not contain any protected health information (PHI), and 
each participant will be identified only according to initials and unique study identifier. 
Following completion of the trial, all data will be kept by SENTA Clinic for two (2) years, as 
mandated.  Electronic data will be stored on password-protected computers using the SENTA 
Clinic’s secure servers.  Access to trial data will be available to study investigators, research 
assistants, and statisticians; however, this data will be de-identified to the maximum of the 
investigators’ capabilities.  Finally, each investigator will declare any financial or other conflicts 
of interests prior to study onset, and at completion. 
Dissemination Policy 
Any manuscripts derived from the study will be written by the investigators, without 
professional writers.  The principal investigators (PI) will be the senior authors.  Other 
investigators who have contributed to the planning and conception; manuscript writing or 
revision; participant recruitment; or data analysis may be named as co-authors on any 
publications.  The results of the study may be presented at national or international scientific 
meetings.  Participants will be informed about study results through local dissemination. In 
order to protect Sponsor’s confidential information and intellectual property rights, any 
proposed publication, presentation or other public disclosure of study must be reviewed and 
approved in writing by Sponsor prior to submission or public disclosure, such approval not to be 
unreasonably withheld. Sponsor will respond to requests for publication or other public 
disclosure within sixty (60) days. 

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