Internal Jugular Vein Compression Collar for Novel Symptomatic Treatment of Venous Pulsatile Tinnitus
Phase: NA
Conditions: Pulsatile Tinnitus
Sponsor: University of North Carolina, Chapel Hill

Template version: January 30, 2020 
Internal Jugular Vein Compression Collar for Novel 
Symptomatic Treatment of Venous Pulsatile Tinnitus,  
IJV Collar for Pulsatile Tinnitus 
Q Collar 
N/A 
Title: 
Short Title 
Drug or Device 
Name(s): 
FDA IND 
Regulatory Sponsor: 
eIRB Number:  
Protocol Date:  
Protocol Number: 
Dr. Brian Sindelar, UNC Department of Neurosurgery 
21-3127
1/24/2022 
NCT05441540
Study Principal Investigator 
Benjamin S. Succop Jr. 
201 S. Elliott Rd 
Chapel Hill, NC 27514 
Phone 828-443-9726 
email: benjamin_succop@med.unc.edu 
Faculty Advisor 
Dr. Brian Sindelar 
170 Manning Drive 
Chapel Hill, NC 27599 
Phone 919-966-1374 
email: bsind@email.unc.edu 

  
 
 
 
 
 
 
 
ii 
TABLE OF CONTENTS 
Table of Contents ................................................................................................................... ii 
Abbreviations and Definitions of Terms .............................................................................. v 
Abstract .................................................................................................................................. v 
Protocol Synopsis .................................................................................................................. vi 
EXAMPLE: Table 1: Schedule of Study Procedures ..................................................... iviii 
1 
BACKGROUND INFORMATION AND RATIONALE ........................................................................ 1 
1.1 
INTRODUCTION ......................................................................................................................................... 1 
1.2 
NAME AND DESCRIPTION OF INVESTIGATIONAL PRODUCT OR INTERVENTION ......................................... 1 
1.3 
FINDINGS FROM NON-CLINICAL AND CLINICAL STUDIES ......................................................................... 2 
1.3.1 
Non-Clinical Studies ......................................................................................................................... 2 
1.3.2 
Clinical Studies ................................................................................................................................. 2 
1.4 
RELEVANT LITERATURE AND DATA ......................................................................................................... 2 
1.5 
COMPLIANCE STATEMENT ........................................................................................................................ 3 
2 
STUDY OBJECTIVES ............................................................................................................................... 3 
2.1 
PRIMARY OBJECTIVE (OR AIM) ................................................................................................................. 3 
2.2 
SECONDARY OBJECTIVES (OR AIM) .......................................................................................................... 3 
3 
INVESTIGATIONAL PLAN ..................................................................................................................... 4 
3.1 
GENERAL SCHEMA OF STUDY DESIGN ...................................................................................................... 4 
3.1.1 
Screening Phase ............................................................................................................................... 4 
3.1.2 
First Visit: Consent, Fitting, Education, Evaluation, Scales ........................................................... 4 
3.1.3 
At Home Use ..................................................................................................................................... 4 
3.1.4 
Second Visit: Reevaluation and Exit Scale ....................................................................................... 4 
3.2 
STUDY DURATION, ENROLLMENT AND NUMBER OF SITES ....................................................................... 4 
3.2.1 
Duration of Study Participation ....................................................................................................... 4 
3.2.2 
Total Number of Study Sites/Total Number of Subjects Projected ................................................... 4 
3.3 
STUDY POPULATION ................................................................................................................................. 4 
3.3.1 
Inclusion Criteria ............................................................................. Error! Bookmark not defined. 
3.3.2 
Exclusion Criteria ............................................................................................................................ 5 
4 
STUDY PROCEDURES ............................................................................................................................. 5 
4.1 
STUDY TREATMENT PHASE ...................................................................................................................... 5 
4.1.1 
Visit 1 ................................................................................................................................................ 5 
4.1.2 
Between Visit (at home) .................................................................... Error! Bookmark not defined. 
4.1.3 
Follow up Visit ................................................................................. Error! Bookmark not defined. 
4.2 
SUBJECT COMPLETION/WITHDRAWAL ..................................................................................................... 6 
4.2.1 
Early Termination Study Visit .......................................................................................................... 6 
5 
STUDY EVALUATIONS AND MEASUREMENTS .............................................................................. 7 
5.1 
SCREENING AND MONITORING EVALUATIONS AND MEASUREMENTS ...................................................... 7 
5.1.1 
Medical Record Review .................................................................................................................... 7 
5.1.2 
Physical Examination ....................................................................................................................... 7 
5.2 
EFFICACY EVALUATIONS .......................................................................................................................... 7 
5.2.1 
Diagnostic Tests, Scales, Measures, etc. .......................................................................................... 7 
5.3 
SAFETY EVALUATION ............................................................................................................................... 7 
6 
STATISTICAL CONSIDERATIONS ....................................................................................................... 8 
6.1 
PRIMARY ENDPOINT ................................................................................................................................. 8 
6.2 
SECONDARY ENDPOINTS .......................................................................................................................... 8 
6.3 
STATISTICAL METHODS ............................................................................................................................ 8 
6.3.1 
Baseline Data ................................................................................................................................... 8 

 
 
 
 
 
 
 
 
iii 
6.3.2 
Efficacy Analysis .............................................................................................................................. 8 
6.3.4 
Safety Analysis .................................................................................................................................. 8 
6.4 
SAMPLE SIZE AND POWER ........................................................................................................................ 9 
6.5 
INTERIM ANALYSIS ................................................................................................................................... 9 
7 
STUDY DEVICE (STUDY DEVICE OR OTHER STUDY INTERVENTION) ................................ 10 
7.1 
DESCRIPTION .......................................................................................................................................... 10 
7.1.1 
Usage .............................................................................................................................................. 10 
7.1.2 
Treatment Compliance and Adherence .......................................................................................... 10 
7.1.3 
Safety .............................................................................................................................................. 10 
8 
SAFETY MANAGEMENT ...................................................................................................................... 11 
8.1 
CLINICAL ADVERSE EVENTS .................................................................................................................. 11 
8.2 
ADVERSE EVENT REPORTING ................................................................................................................. 11 
 
9 
STUDY ADMINISTRATION .................................................................................................................. 12 
9.1 
TREATMENT ASSIGNMENT METHODS ..................................................................................................... 12 
9.2 
DATA COLLECTION AND MANAGEMENT ................................................................................................ 12 
9.3 
CONFIDENTIALITY .................................................................................................................................. 12 
9.4 
REGULATORY AND ETHICAL CONSIDERATIONS ...................................................................................... 12 
9.4.1 
Data and Safety Monitoring Plan ................................................................................................... 12 
9.4.2 
Risk Assessment .............................................................................................................................. 12 
9.4.3 
Potential Benefits of Trial Participation ........................................................................................ 13 
9.4.4 
Risk-Benefit Assessment ................................................................................................................. 13 
9.5 
RECRUITMENT STRATEGY ...................................................................................................................... 13 
9.6 
INFORMED CONSENT/ASSENT AND HIPAA AUTHORIZATION ................................................................ 13 
9.6.1 
Waiver of Consent .......................................................................................................................... 13 
9.6.2 
Waiver of Assent ............................................................................................................................. 14 
9.6.3 
Waiver of HIPAA Authorization ..................................................................................................... 14 
10 
PUBLICATION ......................................................................................................................................... 15 
11 
REFERENCES .......................................................................................................................................... 16 
Appendix ............................................................................................................................... 18 
 

  
 
 
 
 
 
 
 
iv 
ABBREVIATIONS AND DEFINITIONS OF TERMS 
 
 
 
AE 
 
Adverse event 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

  
 
 
 
 
 
 
 
v 
ABSTRACT 
Context:  (Background) 
Tinnitus is a medical condition with a wide variety of causes that is characterized by the 
perception of sound, often described as ringing or buzzing, without an external stimulus. 
Venous pulsatile tinnitus is a specific subtype of tinnitus with limited treatment options 
beyond surgical correction of underlying vascular defect. The clinical diagnostic hallmark of 
venous pulsatile tinnitus is relief of symptoms with light compression of the ipsilateral 
external jugular vein by the physician. 
Objectives: (primary and important secondary objectives) 
This study seeks to pilot an evaluation of whether an external jugular vein compression 
collar approved by the FDA for contact sports can provide symptomatic relief of venous 
pulsatile tinnitus. Furthermore, the study will pilot quality of life impacts of the device. 
Study Design:  
This is a non-blinded, interventional, prospective single cohort pilot study in which 
participants will be asked to evaluate the effect of wearing the collar, if any, on tinnitus 
symptoms. Secondary effects such as adherence, comfort, and quality of life while wearing 
the device will also be evaluated. 
Setting/Participants: 
This study will recruit 20 particpants complaining of pulsatile tinnitus who are patients at 
the UNC Meadowmont ENT outpatient clinic. Inclusion criteria will include those patients 
identified to have pulsatile tinnitus without a medical or surgical treatment upon thorough 
evaluation by the ENT service. Exclusion criteria will be those with non-pulsatile tinnitus, 
age, cerebral infarction (blockage or narrowing in the arteries supplying blood and oxygen 
to the brain) or severe head trauma, medical contraindications to restriction of blood outflow 
via the internal jugular veins, glaucoma, hydrocephalus, recent penetrating brain trauma 
(within 6 months), known carotid hypersensitivity, known increased intracranial pressure, 
idiopathic intracranial hypertension, known intracranial vascular malformation, central vein 
thrombosis, any known airway obstruction, or those not tolerating initial fitting of the collar. 
 
Study Interventions and Measures:  
The intervention device is marketed as the Q Collar, a light jugular vein compression device 
FDA approved for use in contact sports for individuals above the age of 13. 
Main study outcomes will be degree of relief upon application of collar, sustainment of 
relief with home use of the collar, and quality of life metrics administereed at the beginning 
and end of the study. 

  
 
 
 
 
 
 
 
vi 
PROTOCOL SYNOPSIS 
Study Title 
Internal Jugular Vein Compression Collar for Novel Symptomatic 
Treatment of Venous Pulsatile Tinnitus 
 
Funder 
Departmental Funds 
Clinical Phase 
Pilot Study 
Study Rationale 
Venus pulsatile tinnitus is a subtype of tinnitus that is refractory to 
medical treatment. Its defining symptom is patient perception of a 
whooshing sound in time with the heartbeat, and its characteristic 
diagnostic sign is relief of symptoms when the internal jugular vein 
is lightly compressed by the physician during examination. This 
study seeks to apply the defining diagnostic findings to treatment 
through use of a internal jugular vein compression collar approved 
by the FDA for contact sports. 
Study Objective(s) 
Primary  
• 
To determine if an internal jugular vein compression collar 
significantly relieves symptoms of venous pulsatile tinnitus. 
Secondary 
• 
To determine quality of life impacts 
Test Article(s) 
(If Applicable) 
The Q-Collar is a non-invasive device intended to be worn around 
the neck of athletes aged 13 years and older during sports activities 
to aid in the protection of the brain from effects associated with 
repetitive sub-concussive head impacts. 
Study Design 
 
Interventional single cohort pilot study. Data collected at original 
visit vai completion of tinnitus intensity and QOL scales, daily 
during 2-4 week follow up, and at follow up visit. All data collected 
through REDCAP administered scales into REDCAP password 
protected database 
Subject Population 
key criteria for 
Inclusion and 
Exclusion: 
Inclusion Criteria 
1. Subjects age 18 and older 
2. Subjects are diagnosed with pulsatile tinnitus 
3. Subjects are patients at UNC ENT Meadowmont outpatient 
clinic. 
Exclusion Criteria 
1. Known risk factors for or existence of intracranial or 
intraocular hypertension, listed in detail in study protocol. 
Number Of Subjects  
 
20 
Study Duration 
Each subject’s participation will last 2 weeks 

 
 
 
 
 
 
 
 
 
 
vii 
Study Phases 
Enrollment 
Study Treatment 
Follow-Up   
Participants meeting inclusion/exclusion criteria at UNC 
Meadowmont will be invited to participate. Those who consent will 
be fitted with the collar. Then, the at home treatment phase will 
begin where they report on collar efficacy. Finally, a follow up visit 
will be conducted to complete exit surveys.  
Efficacy Evaluations 
Significant improvement in tinnitus symptoms while wearing collar.  
Safety Evaluations 
At intiial visit, team clinician will supervise collar fitting and 
evaluate for significant pain, discomfort, or adverse effect which 
will halt participation for that participant and be recorded. During at 
home study phase, participants will report any adverse effects with 
their daily recording of symptomatic efficacy.  
Statistical And 
Analytic Plan 
One sided t test on tinnitus intensity while wearing collar vs. while 
not wearing collar will evaluate primary endpoint of collar relief 
efficacy. ANOVA analysis of intensity differences will elucidate 
effect of time, if any. One sided t test will evaluate secondary 
endpoints of quality of life 
DATA AND SAFETY 
MONITORING PLAN 
Faculty mentor Dr. Brian Sindelar is monitoring all safety related 
aspects. These include the evaluation of the initial collar fit, collar 
use education, and reporting of adverse events during at home 
period.  

 
viii  
 
 
 
 
 
 
 
EXAMPLE: TABLE 1: SCHEDULE OF STUDY PROCEDURES  
Study Phase 
Screening through 
EPIC 
Initial consenting and 
fitting visit 
Home Use (Daily for 14 
days) 
Follow up visit 
Visit Number 
N/A 
1 
N/A 
2 
Study Days 
0 
1 
2-15 
16 
Informed Consent/Assent 
 
X 
 
 
Review Inclusion/Exclusion 
Criteria 
X 
 
 
 
Demographics/Medical 
History 
 
X 
 
 
Fit Collar 
 
X 
 
 
Adverse Event Assessment 
 
X 
 
 
QOL Data 
 
X 
 
X 
Symptom Relief Data 
 
X 
X 
X 
Adherence/Usage Data 
 
 
X 
 
Adverse Event Reporting 
 
 
X 
 

 
page ix 
  
 
 
 

 
  
 
 
 
1 
1 
BACKGROUND INFORMATION AND RATIONALE 
Section 1 should be no more than 3 – 5 pages. Refer the reader to the applicable grant, or 
attached literature references for more detailed information.  
Introduction 
Tinnitus is a medical condition with a wide variety of causes that is characterized 
by the perception of sound, often described as ringing or buzzing, without an 
external stimulus.1 It is extremely common, and has a prevalence in the United 
States ranging from 10% to 15% of the population.2 Persistent tinnitus can have 
a highly negative impact on quality of life, with individuals suffering from the 
condition manifesting higher rates of anxiety, depression, and lowered self 
esteem3-5.  Pulsatile tinnitus is a specific subtype of tinnitus with limited 
treatment options. It is defined as a “whooshing” sound that pulsates in rhythm 
with the patient’s heartbeat and generally manifests unilaterally.6 Pulsatile 
tinnitus affects over 10% of the total tinnitus population, and it has a variety of 
both vascular, specifically venous, and nonvascular causes.7 Unlike traditional 
tinnitus, medication is ineffective for most causes of pulsatile tinnitus.8  
The provocative physical exam test for venous pulsatile tinnitus consists of the 
physician lightly compressing the internal jugular vein ipsilateral to the side of 
symptoms.9 For patients with any venous cause of pulsatile tinnitus, symptoms 
will be relieved upon compression of the ipsilateral internal jugular vein and 
return when pressure is released by the examiner, a diagnostic finding with 93% 
sensitivity.10  Given that the provocative exam finding for venous pulsatile 
tinnitus is relief of symptoms while compressing the neck, and that in many cases 
effective treatment options are limited for this condition, it is the goal of this 
study to test a FDA approved internal jugular vein compression collar as a 
symptomatic treatment for patients with this condition. By applying and 
sustaining the compression technique used by physicians on exam, it is 
hypothesized that this collar will achieve significant, perhaps even complete 
reduction in patient symptoms. 
 
1.1 Name and Description of Investigational Product or Intervention 
The current FDA approved internal jugular vein compression collar, marketed as the Q 
collar, is manufactured by Q30 Innovations Home. It is designed to be worn around the neck 
of individuals aged 13 and older. It functions by lightly compressing the internal jugular 
vein’s bilaterally, safely increasing intracranial volume and intracranial pressure. The FDA 
approved neck collar device is made of a thermoplastic elastomer that is specifically fitted to 
an individual to provide mild internal jugular vein compression.11  The product was 
developed and confirmed with ultrasonography to confirm appropriate fit and compression 
of the vein based on an athlete’s neck circumference.12   
 
 
 
 

 
  
 
 
 
2 
1.2 Findings from Non-Clinical and Clinical Studies  
(This section is only applicable for drugs, biologics and devices) 
1.2.1 Non-Clinical Studies 
The landmark paper by Smith et al. (2012) and Turner et al. (2012) demonstrated significant 
reduction in axonal injury following internal jugular vein compression in a rodent 
concussion model and this catapulted the translatable research specifically in concussion 
mitigation.13  Interestingly during rodent behavioral testing in the application to blast 
concussive injury, a potential protective benefit of IJV compression against hearing injury 
was discovered by the faculty preceptor of this project, Dr. Brian Sindelar, and his team.14-15 
Through conversations with the student researcher and with colleagues at UNC 
otolaryngology, including faculty attending Dr. Matthew Dedmon, the collar was identified 
as a potential intervention for venous pulsatile tinnitus. 
1.2.2 Clinical Studies 
The use of jugular compression collars (Q-collar) during physical activity has recently been 
shown to reduce white matter alterations associated with head impact exposure in male and 
female athletes in sports including football, hockey, and soccer. Ongoing trials have 
demonstrated improvements in concussion biomarkers through clinical and radiographic 
measures.13, 16-17 
 
1.3 Relevant Literature and Data 
Pulsatile Tinnitus: Overview, Pathophysiology, Diagnosis  
Pulsatile Tinnitus is the auditory perception of rhythmic noises in time with the heartbeat.18 
It can be either vascular or nonvascular in origin, and vascular presentations are divided into 
venous and arterial etiologies.19 In vascular etiologies, the symptomatic presentation is a 
consequence of turbulence in vasculature near the cochlea, hence the synchronization with 
pulse.20 This condition can have significant adverse effects on patient quality of life, leading 
to insomnia, difficulty concentrating, impaired audition, and mental health deterioration.21 
Venous abnormalities are the most common causes of pulsatile tinnitus, particularly 
structural and flow abnormalities in one or multiple intracranial or extracranial venous 
structures secondary to intracranial hypertension or anatomical variation.22  Non-invasive 
imaging is an effective means of diagnosing pulsatile tinnitus, successfully identifying 
relevant phenomena in 40% to 70% of cases.23-24  Furthermore, physical exam alone can 
distinguish venous causes from other ideologies of pulsatile tinnitus.9 Specifically, relief of 
symptoms upon temporary manual neck compression of the ipsilateral IJV detects venous 
etiology with 93% sensitivity, a finding that is replicated with less sensitivity by a Valsalva 
maneuver or by turning the patient’s head toward the side lateralizing with pulsatile 
tinnitus.9-10 
    
Etiologies of Venous Pulsatile Tinnitus  
Venous pulsatile tinnitus is caused by a broad differential of specific etiologies. All 
etiologies involve disturbed flow of an internal jugular vein and/or one of the veins or 
sinuses that drain into it.30 The turbulent flow is conducted by the skull base and mastoids 
to the cochlea, resulting in the perception of pulsating sound.25-26 Broadly, these etiologies 
and their treatments can be classified by location of the abnormality: the lateral sinuses, 
emissary veins, jugular bulb, and internal jugular vein.10 For cases in which the underlying 
etiology cannot be identified and corrected, there are few options for symptomatic 

 
  
 
 
 
3 
management. Cognitive behavioral therapy, meditation, and sound machines have all been 
employed for symptomatic management with limited success.11 
 
Surveys and Scales:  
The Tinnitus Handicap Inventory (THI) is a 25-item validated survey that evaluates the 
degree of impact a patient’s tinnitus has on their quality of life.27 It is currently the first line 
survey for systemic impacts of tinnitus and is attached at the end of this proposal. In 
addition, NIH validated patient reported outcome measurement information system 
(PROMIS) questionnaires on anxiety, depression, physical function, and satisfaction will be 
administered before and after the treatment period to evaluate the collar’s broader impact on 
patient quality of life (see end of proposal).28 Additionally, a custom tinnitus intensity scale 
modeled after the numerical pain scale with be used to assess relief. Lastly, a single item 
Likert scale inquiring about use of the collar when symptoms present will be applied to 
evaluate adherence.  
 
1.4 Compliance Statement 
This study will be conducted in full accordance with all applicable University of North 
Carolina Research Policies and Procedures and all applicable Federal and state laws and 
regulations All episodes of noncompliance will be documented. 
The investigators will perform the study in accordance with this protocol, will obtain 
consent and assent, and will report unanticipated problems involving risks to subjects or 
others in accordance with University of North Carolina IRB Policies and Procedures and all 
federal requirements. Collection, recording, and reporting of data will be accurate and will 
ensure the privacy, health, and welfare of research subjects during and after the study.  
2 
STUDY OBJECTIVES 
The purpose of the study is to determine the preliminary efficacy of an internal jugular vein 
compression collar for treating pulsatile tinnitus. Pilot data, if demonstrative of efficacy, will 
be used to apply for a multicenter grant. 
2.1 Primary Objective (or Aim) 
The primary objective of this study is to determine if an internal jugular vein compression 
collar can relieve symptoms of venous pulsatile tinnitus. 
2.2 Secondary Objectives (or Aim) 
The secondary objectives are to:  
• Determine if the collar effect varies with time 
• Evaluate changes in quality of life as a result of collar use 
• Compare home use with in clinic use 
3 
INVESTIGATIONAL PLAN 
3.1 General Schema of Study Design 
Before contact: Screen for eligibile participants through EPIC 
First Visit: Consent, collect voluntary demographic and QOL data, fit collar, educate on use, 
evaluate symptom relief 
Home Use:  

 
  
 
 
 
4 
3.1.1 Screening Phase 
Potential subjects will be screened using the protocol inclusion and exclusion criteria 
through EPIC. A limited waiver has been requested for this information..    
3.1.2 First Visit: Consent, Fitting, Education, Evaluation, Scales 
During the first visit, potential participants identified through screening will be invited by a 
member of the study team to participate. If they agree, they will fill out consent forms, 
demographics, and preliminary QOL scales through REDCAP, as well as a baseline tinnitus 
intensity scale. At this point, a clinicial research team member not associated with their care 
will supervise fitting of the collar. The patient will be monitored for 10 minutes for adverse 
effects, then asked to complete the scale once more. Lastly, the patient will be educated on 
fitting and use of the collar, specifically not to use for more than 4 hours daily nor while 
sleeping, given the collar with its packaging and its instructions, and sent home for home 
use. 
3.1.3 At Home Use (2 weeks) 
Through a REDCAP link to their email or mobile device, the participants will daily record 
length of time using collar, average tinnitus intensity with and without collar, and any 
discomfort/adversity with collar use for 14 days consecutively. 
3.1.4 Second Visit: Re-evaluation and Exit Scales 
The participant will undergo refitting of the collar and evaluation of symptomatic relief 
under medical supervision once again. The participant will then complete QOL surveys 
again and an exit survey. This concludes participation. 
3.2 Study Duration, Enrollment and Number of Sites 
3.2.1 Duration of Subject Study Participation 
16 days: 1 day for consent, fitting, and initial evlauation; 14 days for at home use, and 1 day 
for follow up.  
3.2.2 Total Number of Study Sites/Total Number of Subjects Projected 
The study will be conducted at approximately 1 investigative site in the United States. This 
site is the UNC Meadowmont ENT outpatient clinic.  
Recruitment will stop when approximately 20 subjects are recruited. It is expected that 
approximately 22 subjects will be enrolled to produce 20 evaluable subjects.  
3.3 Study Population 
3.3.1 Subject Inclusion Criteria 
1) Male or female age 18 years and older 
2) Diagnosis of venous pulsatile tinnitus 
3) Patient at UNC ENT Meadowmont Clinic 
3.3.2 Subject Exclusion Criteria 
• Increased presence of acid in the body or excessive blood alkalinity 
• Open head injury (including in or around the eye) within the past six months 
• Pseudotumor cerebri (false brain tumor) 
• Presence of brain or spinal shunt 
• Known seizure disorder 
• Known airway obstruction 
• Increased likelihood of blood clotting (coagulation) 

 
  
 
 
 
5 
• Skin injury, rash, or other abnormality on or around the neck 
• age <18 
• unable to provide written consent,  
• history of neurological deficits, 
• previous cerebral infarction (blockage or narrowing in the arteries supplying blood 
and oxygen to the brain) 
• severe head trauma 
• medical contraindications to restriction of blood outflow via the internal 
jugular veins 
• glaucoma (narrow angle or normal tension - increased pressure in the eyes), 
• hydrocephalus (increased fluid on the brain) 
• recent penetrating brain trauma (within 6 months), 
• known carotid hypersensitivity 
• known increased intracranial pressure 
• idiopathic intracranial hypertension  
• known intracranial vascular malformation (e.g. aneurysm, arteriovenous 
malformation, cavernoma)  
• central vein thrombosis  
• not tolerating initial fitting of collar. 
• Known pregnancy (this is not a direct contraindication but is being made out of an 
abundance of caution) 
• Inability to speak or comprehend English (this pilot study does not have funding for 
translators) 
 
4 
STUDY PROCEDURES 
4.1 Study Treatment Phase 
Pre consent: identification of eligility according to inclusion/exclusion factors by chart 
review 
4.1.1 Visit 1 (at Meadowmont ENT clinic visit) 
• Explanation of Study 
• Invitation to participate 
• Consenting of participant 
• Tinnitus intensity and quality of life scales through REDCAP 
•  Fitting of collar 
• Evaluation of pain or discomfort 
• 10 minute observation of patient with fitted collar 
• Readministration of tinnitus intensity scale 
• Education on collar use and misuse (emphasis on no more than 4 hours daily and 
only while awake 
• Transfer of collar and materials to participant 
4.1.2 Between Visit (at home) phase 
Patient wears collar for <4 hours total while awake for symptomatic relief as needed  

 
  
 
 
 
6 
Patient reports daily average tinnitus intensity with and without collar, length of use, and 
any adverse events through REDCAP email/text link 
Continues daily for 14 days 
4.1.3 Follow up visit 
Reevaluation of tinnitus baseline without collar and with collar under medical 
supervision 
Collection of collar and instruction materials 
QOL surveys through REDCAP 
Qualitative Exit Survey on collar 
 
4.2 Subject Completion/Withdrawal 
Example: Subjects may withdraw from the study at any time without prejudice to their care.  
They may also be discontinued from the study at the discretion of the Investigator for lack of 
adherence to study treatment or visit schedules, development of exclusion criteria, or 
adverse events  The Investigator or the Faculty Advisor may also withdraw subjects who 
violate the study plan, or to protect the subject for reasons of safety or for administrative 
reasons.  It will be documented whether or not each subject completes the clinical study. If 
the Faculty Advisor becomes aware of any serious, related adverse events after the subject 
completes or withdraws from the study, they will be recorded in the source documents and 
on the CRF. 
4.2.1 Early Termination Study Visit 
Subjects who withdraw from the study will have all records deleted from the REDCAP 
database except for adverse events, which will be reported by the Faculty Advisor to the 
IRB. 

 
  
 
 
 
7 
5 
STUDY EVALUATIONS AND MEASUREMENTS 
5.1 Screening and Monitoring Evaluations and Measurements 
5.1.1 Medical Record Review 
Diagnosis of venous pulsatile tinnitus 
Inclusion/Exclusion criteria 
Year of Birth 
Time since diagnosis (chronicity of current disease) 
5.1.2 Physical Examination 
• Date of birth 
• Gender 
• Race 
5.2 Efficacy Evaluations 
5.2.1 Diagnostic Tests, Scales, Measures, etc. 
• Primary endpoint: symptom relief 
o Tinnitus aural intensity scale before and after collar administration at each 
visit and once daily for with collar and without collar intensity 
• Secondary endpoint: QOL Impact 
o Tinnitus Handicap Index (Once at beginning of study, once at end) 
o Patient Reported Outcome Measurement Information System (PROMIS) 
scales in depression, anxiety, physical function, and satisfaction 
• Secondary endpoint: Temporality 
o Aural intensity scale submissions will be plotted and compared over time 
course of study 
• Secondary endpoint: Homes vs. clinic use 
o Supervised tinnitus intensity scale measurements will be compared to at 
home measurements to evaluate if perception of symptomatic intensity varies 
with environment 
5.3 Safety Evaluation 
Example: Subject safety will be monitored by observation and intervention of adverse 
events during the physician-supervised fitting period at the beginning of the study and by 
education of the participants to discontinue use of the collar with any significant change in 
physical well-being or onset of new symptoms and immediate reporting of that occurrence 
to the PI and Faculty Advisor through the REDCAP link. 

 
  
 
 
 
8 
6 
STATISTICAL CONSIDERATIONS 
6.1 Primary Endpoint 
The primary efficacy endpoint will be the change in tinnitus intensity with and without the 
collar averaged within participants for each completion and across participants the study and 
6.2 Secondary Endpoints 
Secondary endpoints will include the following: 
• The change in participant quality of life 
• The effect of time on symptomatic relief 
•  The effect of medical supervision on symptomatic relief 
• Adverse events (none are expected; however, the unlikely occurrence will be tabulated 
or a lack thereof shall be reported) 
 
6.3 Statistical Methods 
6.3.1 Baseline Data  
Baseline and demographic characteristics will be summarized by standard descriptive 
summaries (e.g. means and standard deviations for continuous variables such as age and 
percentages for categorical variables such as gender). 
6.3.2 Efficacy Analysis 
The primary analysis will be based on an intention to treat approach and will include all 
subjects who complete the study.   
The primary efficacy endpoint will be the change in tinnitus intensity with and without the 
collar, averaged within and across each patient’s completion of the tinnitus scales. This 
means that there will be 16 paired collar and no collar measurements per patient, one at each 
clinic visit and one each day during the 14 day intervening period. The significance of this 
change will be evaluated using a unidirectional t-test.  
Secondary endpoints will include the following: 
• Temporality of symptom relief 
o Subjects with and without collar scores will be averaged for each day of the 
study, ANOVA testing will evaluate for the presence of a significant time 
component. 
• Supervised vs. unsupervised use 
o The mean relief recorded at the first and second visit will be averaged and 
compared avross patients with the mean relief recorded during at home use 
using a bidirectional t test. 
• QOL impacts 
o Evaluated for each scale using bidirectional t test 
6.3.3 Safety Analysis 
Adverse events are not expected; however,  all subjects entered into the study at Visit 1 will 
be included in the safety analysis. The frequencies of AEs by type, body system, severity 
and relationship to study drug will be summarized if at all present. SAEs (if any) will be 
described in detail. 
AE incidence will be summarized along with the corresponding exact binomial 95% two-
sided confidence intervals. 

 
  
 
 
 
9 
6.4 Sample Size and Power 
For the principal endpoint, the tinnitus intensity scale ranges from 1-10. Assuming an 
average tinnitus intensity of 5 and a standard deviation of plus or minus 2 (such that 95% of 
the venous pulsatile tinnitus population has tinnitus intensity between 1 and 9). Intensity 
scale measurements will be averaged across individual submissions and across participants. 
With 16 paired evaluations per participant and 20 participants total, that creates 320 non 
collar tinnitus intesnity measures 320 collar intensity measures. 
Setting an alpha of p=.05 and a power of 0.8 (beta=0.2), we expect a minimum effect of a 1 
point decrease between the no collar and collar measurements. To be conservative, we will 
preserve the 2 point standard deviation assumed for the baseline measure to apply to the 
collar relief measure. These parameters allow us to evaluate the viability of our sample size.  
 
 
Where n is the number of analyses that will allow our minimum effect size to be significant 
Substitution lends us the following 
ng = (1.96+ 0.8416)2*(22+22)/(2)2 
ng = 15.86 
 
Not only is our overall study well in exceeding the number of intensity measurement 
differences needed to measure a significant effect; we will be able to assess the significant 
effect within each participant, given that each participant will complete both the with and 
without collar scales a total of 16 times. This gives our study strong internal and external 
validity. 
 
6.5 Interim Analysis 
Not planned. Significant safety adverse events would lead to termination of study. 
 

 
  
 
 
 
10 
7 
STUDY DEVICE (STUDY DEVICE OR OTHER STUDY INTERVENTION) 
7.1 Description 
7.1.1 Usage 
The collar can be worn while awake for no more than 4 hours daily by participants who 
meet the inclusion/exclusion criteria. This point shall be educated to participants who enroll. 
7.1.2 Treatment Compliance and Adherence 
The daily scales completed by participants during the at home period will contain reminders 
of the safety and adherence stipulations of the collar 
7.1.3 Safety 
Subject safety will be monitored by observation and intervention of adverse events during 
the physician-supervised fitting period at the beginning of the study and by education of the 
participants to discontinue use of the collar with any significant change in physical well-
being or onset of new symptoms and immediate reporting of that occurrence to the PI and 
Faculty Advisor through the REDCAP link. 
 
 

 
  
 
 
 
11 
8 
SAFETY MANAGEMENT 
8.1 Clinical Adverse Events 
Clinical adverse events (AEs) will be monitored throughout the study.  
8.2 Adverse Event Reporting 
Since the study procedures are not greater than minimal risk, SAEs are not expected. If any 
unanticipated problems related to the research involving risks to subjects or others happen 
during the course of this study (including SAEs) they will be reported to the IRB in 
accordance with CHOP IRB SOP 408: Unanticipated Problems Involving Risks to Subjects. 
AEs that do not meet prompt reporting requirements will be summarized in narrative or 
other format and submitted to the IRB at the time of continuing review (if continuing 
reviews are required), or will be tracked and documented internally by the study team but 
not submitted to the IRB (if continuing reviews are not required).  

 
  
 
 
 
12 
9 
STUDY ADMINISTRATION 
9.1 Treatment Assignment Methods 
There will be no randomization or blinding of participants. 
9.2 Data Collection and Management 
All data will be collected and stored in a password-protected redcap database available only 
to access by study personnel. All study personnel are trained and certified in HIPAA. Data 
collection will occur through individualized links to REDCAP database administered on 
secure clinic iPad during visits or sent to participant phone/email during home phase. 
9.3 Confidentiality 
All data and records generated during this study will be kept confidential in accordance with 
Institutional policies and HIPAA on subject privacy. Data and records will not be used for 
any purpose other than conducting the study. All data and records will be stored in password 
protected REDCAP database.  
No identifiable data will be used for future study without first obtaining IRB approval or 
determination of exemption.  
9.4 Regulatory and Ethical Considerations 
9.4.1 Data and Safety Monitoring Plan 
The faculty advisor will oversee all aspects of safety monitoring. These include the 
supervised fitting and collar education under observation of research team position 
and the reporting of any adverse events during the at home phase. 
The faculty advisor will monitor and review the study progress, subject safety, and the 
accuracy and security of the emerging data. 
9.4.2 Risk Assessment 
Not Greater than Minimal: 
- 
Psychological 
o Wearing the collar might be embarrassing for some patients. This is averted 
through a flexible at home protocol in which they are only asked to wear the 
collar on an as needed basis for symptomatic relief and report their efficacy. 
Patients will be allowed to withdraw from the study at any time. 
- 
Confidentiality 
o Any study has potential consequences a breach of confidentiality, this study 
will avoid those consequences through maintenance of the data in a password 
protected REDCAP database accessible only to the research team, all of 
whom are HIPAA certified. 
- 
Discomfort 
o The device is FDA approved for contact sports, and there are no adverse risks 
for the indicated population. However there is a possibility that patients will 
feel discomfort when wearing it. Care will be made to ensure the fitting is 
optimize the patient's needs. Possibility of mild discomfort if collar used 
incorrectly; this will be averted by counseling patients to not use the collar 
while sleeping and by fitting the collar correctly to the neck circumference of 
the subject at the initial visit.  
 

 
  
 
 
 
13 
9.4.3 Potential Benefits of Trial Participation 
Direct Benefits: Immediate symptom and quality of life improvement while wearing the 
collar during the study. 
Indirect Benefits: contributing to widespread approval and access of color are used for 
venous pulsatile tinnitus population if effective in relieving symptoms by generating pilot 
data that will be used to justify clinical trials. 
9.4.4 Risk-Benefit Assessment 
Given that the device is approved by the FDA in a different setting, that is, contact sports, 
and given that use of the device in this application will follow all FDA recommendations 
regarding duration, use, and contraindications, we anticipate minimal risk to participants in 
the study. The benefits for participants are high given that it is likely the Color will be 
effective based on the principle of its use aligning directly with the chief diagnostic physical 
exam findings of this condition, that is, relief of symptoms upon light compression of the 
internal jugular vein. Therefore, in light of these observations, and given the fact that this 
condition has limited treatment options outside of surgery, we determine it worthwhile to 
proceed with the study. 
9.5 Recruitment Strategy 
A HIPAA waiver has been requested for the screening of eligible participants. The PI will 
then screen EPIC for patients meeting the exclusion and inclusion criteria to identify eligible 
participants. Recruiting will occur by a member of the study team not responsible for the 
patient’s direct care engaging them during their clinic visit independent of their provider at 
UNC ENT Meadowmont. 
 
9.6 Informed Consent/Assent and HIPAA Authorization 
The principal investigator or one of the physician investigators not responsible for the 
patient’s care will approach a patient meeting exclusion and inclusion criteria in person 
during one of their regular visits at UNC Meadowmont outpatient clinic. This will occur in 
the examination room after the patient’s care provider has stepped out. At this point the 
patient will be asked about their interest in hearing about and possibly participating in a 
study that could help their tinnitus. If the patient acquiescence, the team member will then 
explain the study as well as its potential direct benefits and risks to the patient, emphasizing 
that the ultimate goal is scientific advancement instead of improved care. If the patient 
acquiesces, the consent forms and HIPAA form will be shared and explained to them. If they 
are still willing to participate, they will sign the forms and become a participant. 
9.6.1 Individuals with Limited English Proficiency  
For Spanish speaking eligible to participate, a certified translator either in person or over the 
phone will be used to help explain the study. Spanish consent forms and HIPAA forms will 
be provided. 
9.6.2 Waiver of HIPAA Authorization 
A limited waiver of HIPAA has been requested for identifying prospective patients. 
Prospective patients will be documented in REDCAP and deleted from the study database 
if they decline participation. 

 
  
 
 
 
14 
10 PUBLICATION 
These data will be submitted for publication in a credentialed academic journal relevant to 
the field of otolaryngology and also submitted to a relevant academic conference for 
presentation as an abstract/poster. Data will only be published in aggregate, all identifying 
characteristics will be deleted prior to analysis and publication. 
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28 Patient-Reported Outcomes Measurement Information System Database 
https://commonfund.nih.gov/promis/index  
 
 
 
 

 
  
 
 
 
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APPENDIX 
All relevant scales, documents, and figures have been appended to the IRB