Clinical trial NCT04292470
Conditions: GERD
Sponsor: University of California, Davis
Start date: 2020-11-05; Completion date: 2021-11-04
Enrollment: 7 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This study is designed to assess the physiologic and behavioral mechanisms associated with enhanced medication effects in adult patients with functional GERD-related symptoms.

Detailed description:
Subjects will complete questionnaires regarding their GERD-related symptoms and have a visit with a study clinician regarding their symptoms. Heart rate variability and galvanic skin response will be measured in the patient-provider dyads and the visits video recorded. Subjects will receive a two-month supply of amitriptyline (10 mg/day), along with instructions for taking it. Subjects will complete a daily GERD symptom diary during the first and eighth weeks of the study. At the end of the 8-week observation period, subjects will complete follow-up measures of GERD symptom severity and quality of life.

Arms: arm 1: Amitriptyline 10 mg daily
Interventions: intervention 1: Amitriptyline
Intervention descriptions: intervention 1: Amitriptyline tablet

Protocol documents:
Prot_SAP_000.pdf: 
 
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Version 11.0 
 
 
7 July 2021 
Physiology of GERD and Treatment Response 
 
Principal Investigator:   
Michelle L. Dossett, MD, PhD, MPH 
Assistant Professor,  
Division of General Medicine, Geriatrics & Bioethics 
University of California, Davis 
 
Supported by: 
The National Center for Complementary and Integrative Health 
K23 AT009218 
 
 
NCT 04292470 
 
 


 
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7 July 2021 
Tool Revision History 
Version Number: 2 
Version Date: 01/17/2020 
Summary of Revisions Made: Blood draw added 
Version Number: 5 
Version Date: 05/20/2020 
Summary of Revisions Made: Added Study Pages & Epic lists as recruitment options 
 
 
 
 
Added Physician Satisfaction Questionnaire 
 
 
 
 
Added option to conduct visit 2 remotely 
Version Number: 07/28/2020 
Version Date: 6 
Summary of Revisions Made: Added the additional option of using a video telehealth platform to  
conduct study visits.  
 
 
 
 
Added Appendix B.3 COVID-19 symptom screening. 
Added Appendix D.14 Impressions of the Study Physician 
Questions 
Modified Appendix E: Standard and Expanded Visits Scripts6 
Modified B.1 Telephone Pre-Screening Script 
Added another option for Provider Study Flyer 
 
Version Number: 7 
Version Date: 11/18/2020 
Summary of Revisions Made: Added the option of reviewing patients’ pH study results in EPIC  
in order to identify potentially eligible study subjects as part of the 
recruitment approach. 
 
Version Number: 8 
Version Date: 12/23/2020 
Summary of Revisions Made: Adjusted eligibility age to include any adults from ages 24 to 70. 
 
Version Number: 9 
Version Date: 3/12/2021 
Summary of Revisions Made: Added additional recruitment methods including sending letters 
and using MyChart messages.  
 
Version Number: 10 
Version Date: 6/10/2021 
Summary of Revisions Made: Added UCDH Otolaryngology Reflux Clinic as a recruitment site. 
 
Version Number: 11 


 
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7 July 2021 
Version Date: 7/7/2021 
Summary of Revisions Made: Added second group of eligible subjects – individuals with GERD 
who would be eligible for a prescription for Omeprazole 20 mg per day. 
 


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TABLE OF CONTENTS 
FULL PROTOCOL TITLE ..........................................................................................................1 
PREFACE ......................................................................................... Error! Bookmark not defined. 
Tool Revision History ..................................................................................................................2 
TABLE OF CONTENTS ..............................................................................................................4 
STUDY TEAM ROSTER ...........................................................................................................7 
PARTICIPATING STUDY SITES .............................................................................................7 
PRÉCIS ........................................................................................................................................7 
1. STUDY OBJECTIVES..............................................................................................................8 
1.1      Primary Objective .............................................................................................................8 
1.2 
Secondary Objectives.......................................................................................................8 
2. BACKGROUND AND RATIONALE .....................................................................................9 
2.1 
Background on Condition, Disease, or Other Primary Study Focus ...............................9 
2.2 
Study Rationale ..............................................................................................................10 
3. STUDY DESIGN ......................................................................................................................12 
4. SELECTION AND ENROLLMENT OF PARTICIPANTS ...............................................13 
4.1 
Inclusion Criteria ...........................................................................................................13 
4.2 
Exclusion Criteria ..........................................................................................................13 
4.3       Study Enrollment Procedures ........................................................................................15 
5. STUDY INTERVENTIONS ...................................................................................................18 
5.1   Interventions, Administration, and Duration .....................................................................18 
5.2   Handling of Study Interventions ........................................................................................19 
5.3   Concomitant Interventions .................................................................................................19 
5.4   Adherence Assessment ......................................................................................................19 
6. STUDY PROCEDURES .........................................................................................................21 
6.1 
Schedule of Evaluations for Subjects/Patients ............... Error! Bookmark not defined. 
6.2 
 Description of Evaluations ............................................................................................23 
6.2.1        Telephone Screening (Day -3o to -7) .....................................................................23 
6.2.3 
Blinding..................................................................................................................25 
6.2.4 
Post-Intervention Measures (Day 0) ......................................................................26 
6.2.5 
Completion/Final Evaluation .................................................................................26 


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7. SAFETY ASSESSMENTS ......................................................................................................28 
7.1 
Specification of Safety Parameters ................................................................................29 
7.2 
Methods and Timing for Assessing, Recording, and Analyzing Safety Parameters .....29 
7.3 
Adverse Events and Serious Adverse Events ................................................................30 
7.4 
Reporting Procedures .....................................................................................................30 
7.5 
Follow-up for Adverse Events .......................................................................................30 
7.6 
Safety Monitoring ..........................................................................................................31 
8. 
INTERVENTION DISCONTINUATION.........................................................................31 
9. STATISTICAL CONSIDERATIONS ...................................................................................31 
9.1 
General Design Issues ....................................................................................................31 
9.2 
Sample Size and Randomization ...................................................................................33 
9.3  
Definition of Populations ...............................................................................................33 
9.4 
Interim Analyses and Stopping Rules ............................................................................34 
9.5 
Outcomes .......................................................................................................................34 
9.5.1 Primary Outcome   .....................................................................................................36 
9.5.2 Secondary Outcomes .................................................................................................36 
9.6 
Data Analyses ................................................................................................................37 
10. DATA COLLECTION AND QUALITY ASSURANCE ...................................................37 
10.1 
Data Collection Forms ...................................................................................................37 
10.2 
Data Management ..........................................................................................................38 
10.3 
Quality Assurance ..........................................................................................................38 
10.3.1 
Training ..................................................................................................................38 
10.3.3 
Metrics ...................................................................................................................38 
10.3.4 
Protocol Deviations ................................................................................................38 
10.3.5 
Monitoring .............................................................................................................38 
11. PARTICIPANT RIGHTS AND CONFIDENTIALITY ....................................................38 
11.1 
Institutional Review Board (IRB) Review .....................................................................38 
11.2 
Informed Consent Forms ...............................................................................................39 
11.3 
Participant Confidentiality .............................................................................................39 
11.4 
Study Discontinuation ....................................................................................................39 
12. POTENTIAL BENEFITS .....................................................................................................40 
12.1 
Potential Benefits to Participating Individuals ..............................................................40 
13. COMMITTEES......................................................................................................................40 


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14. PUBLICATION OF RESEARCH FINDINGS ....................... Error! Bookmark not defined. 
15. REFERENCES  ......................................................................................................................40 
16. LIST OF SUPPLEMENTS/APPENDICES .........................................................................47 
 


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     STUDY TEAM ROSTER - key personnel 
Michelle L. Dossett, MD, PhD, MPH, Principal investigator  
Juan Carlos Garcia, MD, Co-investigator  
Stephen G. Henry, MD, MSc, Co-investigator 
Richard L. Kravitz, MD, MSPH, Co-investigator 
 
PARTICIPATING STUDY SITES 
University of California, Davis  
Division of General Medicine 
4150 V Street, Suite 2400 
Sacramento, CA 95817 
Phone: 916-734-7005 
Email: mdossett@ucdavis.edu 
 
PRÉCIS  
 
Study Title: Physiology of GERD and Treatment Response 
 
Objectives  
Primary Aim: To determine in a randomized controlled trial (n=60) whether an expanded, 
compared to a standard, provider visit can augment the effects of a medication targeting 
traditional or functional GERD symptoms. 
Secondary Aims:  
1. To identify physiologic markers of enhanced therapeutic relationships.  
2. To identify patient and physician behaviors associated with GERD symptom 
improvement. 
Design and Outcomes   
This is a randomized controlled trial to assess the physiologic and behavioral mechanisms 
associated with augmented medication effects in adult patients with functional GERD-
related symptoms.   
Subjects will be randomized to receive one of two different semi-scripted visit types – 
either a “standard visit” modeled after an empathic, conventional primary care evaluation 
or an “expanded visit” modeled after an integrative medicine consultation. During the 
visit, we will measure heart rate variability (HRV) and galvanic skin response (GSR) in 
the patient-provider dyads; in addition, we will video record the interactions for later 


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analysis of behavioral responses. Subjects will receive a two-month supply of 
amitriptyline (10 mg/day) or omeprazole (20 mg/day, depending upon the nature of their 
GERD symptoms), along with instructions for taking it. Following the visit, subjects will 
complete questions assessing their relationship/rapport with the study provider. Subjects 
will complete a daily GERD symptom diary during the first and eighth weeks of the 
study. At the end of the 8-week observation period, they will complete follow-up 
measures of GERD symptom severity and quality of life. 
Interventions and Duration  
Subjects will have a single visit with a “study provider,” a physician or nurse practitioner 
who they have never previously met. Subjects will complete a daily symptom diary for 
the 1st and 8th weeks following this visit and return for a second study visit in which they 
will complete questionnaires and be debriefed by a member of the study team. 
Sample Size and Population   
We plan to enroll 60 subjects with functional GERD, age 24-70 with heartburn symptoms 
3 or more days per week.  Thirty subjects will be randomized to the expanded visit 
intervention and 30 subjects will be randomized to the standard visit intervention (1:1 
expanded vs. standard randomization).  We will also enroll approximately 5-6 physicians 
or nurse practitioners and stratify randomization by study provider such that each 
provider will see 10-12 subjects (5-6 expanded visits and 5-6 standard visits).   
1. STUDY OBJECTIVES 
The patient-provider relationship is central to the art of medicine and affects a range of health 
outcomes. However, the specific benefits, and exact mechanisms, by which this relationship 
supports the healing process is poorly understood. Emerging data suggests that physiologic 
biomarkers such as galvanic skin response (GSR) and heart rate variability (HRV) are 
associated with empathy and correlated with the complex verbal and non-verbal behaviors of 
patients and providers during an encounter. Physiologic synchrony in patient-provider dyads 
and supportive non-verbal behaviors may be associated with subsequent health outcomes. This 
study will test these hypotheses using GERD as a model condition. 
     1.1     Primary Objective 
To determine in a randomized controlled trial whether an expanded, compared to a 
standard, provider visit can augment the effects of a medication targeting functional 
GERD symptoms. 
  1.2     Secondary Objectives 
1. To identify the physiologic responses/markers associated with improvement in 
GERD symptom severity in response to an enhanced vs. standard provider visit and 
amitriptyline or omeprazole. 
2. To determine whether an expanded patient-provider visit modeled after an 
integrative medicine consultation leads to more supportive provider behaviors, an 
enhanced patient-provider interaction, and greater improvements in GERD 
symptom severity compared to a standard provider visit.   


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2. BACKGROUND AND RATIONALE 
2.1 
Background on Condition, Disease, or Other Primary Study Focus 
The patient-physician relationship is central to the art of medicine1,2. The quality of 
this relationship affects a range of health outcomes, from irritable bowel3 and cold 
symptoms4 to blood pressure, pain levels, and diabetes outcomes5–8. However, the 
specific benefits, and exact mechanisms, by which this relationship supports healing 
remain poorly understood. Previous work has demonstrated that when providers 
maintain eye contact, actively listen, and express empathy, their patients improve more 
after receiving a placebo than patients receiving care from apparently more detached 
providers3,4. Though studies have suggested a role for communication skills and both 
cognitive and emotional components of empathy, the variety of measures used and 
lack of clarity in definitions have limited the interpretation of this work5,6,9,10.  
In most conventional medical settings, practice demands have resulted in reduced 
time to focus on relational aspects of care. Concomitantly, medical educators and 
professional societies have called for greater emphasis on humanism, patient-centered 
care, and improved patient-provider communication11,12. Indeed, patients are 
frequently stressed/in distress when they visit a physician13. Perceived lack of time 
and anxiety about the visit likely contributes to this stress, one manifestation of which 
is white coat hypertension14. 
The public has become increasingly interested in complementary and integrative 
medicine (IM) healing approaches in which patient-provider dynamics often differ 
substantially from most conventional medical visits15–19. IM providers frequently 
spend more time with patients and ask questions that are quite different from those 
asked during conventional visits. The IM consultation process may produce enhanced 
placebo effects19. It is unclear whether these effects represent a form of interpersonal 
healing20, an enhanced patient-provider relationship (e.g., increased perceived 
empathy or trust), or simply provide patients with the opportunity to reflect on their 
symptoms in a safe and non-judgmental space (a form of therapeutic narrative 
medicine21) creating an openness to perceiving symptoms differently and enhancing 
coping22. Some patients feel “more heard” by IM providers23. IM providers may make 
patients feel more “at ease” and relaxed, promoting a physiologic response (e.g., 
reduced heart rate and blood pressure) similar to that elicited by meditation and other 
mind body techniques24. Feeling less stressed during a medical visit may create an 
openness to change and improved memory of, and follow-through with, the 
provider’s recommendations25. Yet there are few studies of these interactions and 
they largely rely upon patient interviews or responses to surveys15–18. 
Gastroesophageal reflux disease (GERD) is one of the most prevalent health-related 
conditions in the Western world with prevalence estimates ranging from 20-40%26,27. 
GERD is primarily a clinical diagnosis, characterized by symptoms of heartburn and 
acid reflux. It is associated with decreased health-related quality of life and 
significant healthcare costs and lost productivity28,29. Standard treatment includes 
antacids, H2 receptor blockers, and proton pump inhibitors (PPIs), with the latter 


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generally regarded as the most effective of these therapies and is generally used as an 
initial treatment for patients who first present with GERD symptoms. Nonetheless, 
many patients experience continued symptoms despite taking PPIs30. Many patients 
who do not find relief with PPIs have functional heartburn symptoms and/or co-
occurring dyspepsia symptoms (e.g., upper abdominal discomfort, bloating, and gas) 
that do not respond well to this class of medication31,32. Moreover, awareness of the 
interconnections between the central nervous and gastrointestinal systems has led to 
the recognition that stress can profoundly affect gastrointestinal (GI) symptoms, such 
as GERD33, suggesting that interventions targeting these pathways may improve 
symptoms34. Notably, the placebo response rate in trials of GERD medications can be 
as high as 40%35.  
Many individuals with GERD symptoms who do not respond to PPIs have functional 
heartburn which is defined as less than 4% acid exposure on pH manometry and 
esophageal hypersensitivity36,37. These patients respond better to neuromodulators 
such as tricyclic antidepressants, serotonin reuptake inhibitors, gabapentin, and other 
agents.   
Amitriptyline is a tricyclic antidepressant originally used to treat depression but now 
frequently prescribed in low doses to treat functional GERD-related symptoms as 
well as functional dyspepsia, irritable bowel, fibromyalgia, and interstitial cystitis as 
well as other pain-related conditions36,38.  
Omeprazole is a PPI that is used as a first line treatment for patients who initially 
present with GERD symptoms.  
2.2 
Study Rationale 
Studies are beginning to reveal the neural 
correlates of empathy, both in general39 and 
in patient-provider relationships40,41. 
Activation of specific neural pathways 
drives changes in autonomic nervous 
system regulation42, resulting in 
downstream changes in physiologic 
biomarkers such as galvanic skin response 
(GSR) and heart rate variability (HRV)43,44. 
A growing body of research has identified 
concordance in physiologic biomarkers 
between individuals. An excellent review 
of this topic, also known as “interpersonal autonomic physiology” or “physiologic 
synchrony,” has been published45. The authors reviewed 61 studies covering 
relationships between therapist and client, couples, mother and child, teammates, and 
other relationships. There were 8 studies of the therapist-client relationship which 
examined either heart rate (HR) or skin conductance/galvanic skin response (GSR). 
Multiple studies found positive correlations between empathy ratings and physiologic 
synchrony. The study I have proposed would be the first to examine physiologic 
biomarkers in the context of physician-patient interactions in a medical setting. 
1. Provider statement 
or behavior
2. Patient’s neural 
response
3. Change in autonomic 
activity
4. Patient statement 
or behavior
6. Change in autonomic 
activity
5. Provider’s neural 
response
Provider
Patient
Figure 1: Proposed model for mechanisms 
underlying the patient-provider relationship


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As illustrated in Figure 1 above, we hypothesize that moment-to-moment autonomic 
changes in patients and providers over the course of a visit collectively influence 
perceptions of the encounter (part of the “neural response”) and response to treatment 
and that improved treatment response is associated with increased concordance in these 
autonomic changes.  
GSR and HRV can also be used to assess relative physiologic stress vs. relaxation46. 
Typically GSR and HR decrease and high frequency HRV increases in the relaxed 
state24,47,48. While empathic visits may theoretically reduce patients’ allostatic load 
and distress49, this hypothesis has not been studied rigorously. Newer computational 
approaches incorporating complexity theory to the analysis of physiologic data50 have 
yielded valuable insights to the study of human disease (e.g., decreased HRV is 
associated with increased cardiovascular mortality51,52) and the effects of integrative 
modalities such as tai chi53,54. There is limited data using these approaches to study 
client-therapist interactions55–57. 
Social psychologists have developed and validated a variety of coding schemes to 
analyze providers’ verbal and non-verbal behaviors and to link these behaviors with 
patient satisfaction, understanding, trust, rapport, empathy, and a variety of related 
factors9,58–63. This rich literature has yielded many insights and a variety of tools used 
in studies of physician-patient communication, but rarely have these tools been linked 
with physiology or health outcomes7.  
Dr. Dossett recently observed that an “expanded” provider visit modeled after a visit 
to an IM provider was more effective in decreasing heartburn and dyspepsia 
symptoms in patients with GERD than a “standard” provider visit modeled after an 
empathic conventional medical visit64. This study used a script of pre-determined 
questions for each visit type. The standard visit script included questions about 
GERD history, symptoms, prior evaluation and treatments, and past medical history. 
The expanded visit script included the same questions plus additional questions that 
inquired about their GI symptoms, non-GI symptoms, and overall temperament. Thus, 
the main differences between the visits were the length of time spent with the subject 
and the additional questions that were asked. Many of the subjects in this study were 
already taking pharmaceutical medications for GERD, suggesting that symptom 
improvement resulting from the expanded provider visit may enhance the efficacy of 
some medications in providing adequate symptom relief. We intend to formally test 
this hypothesis, that augmented patient-provider visits can enhance medication-
related benefits, in this current study.   
While some may argue that increasing visit length is impractical in conventional 
healthcare settings, one reason why payers will not adequately reimburse for 
increased visit lengths is the lack of data linking visit length with health outcomes. 
Increased visit length has been associated in clinical practice with reduced number of 
prescriptions and increased patient satisfaction, engagement, and quality of care65–67. 
Other studies suggest mechanisms by which provider communication (verbal & non-
verbal) may affect health outcomes68. Yet we really do not know what makes longer 
visits more effective. By better understanding the mechanisms that make the 
expanded visit intervention effective, we will be able to make informed decisions 


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regarding future changes to this intervention and adaptations that may make it more 
feasible in today’s healthcare environment.  
3. STUDY DESIGN 
Study design: Single-center, single-blind, randomized controlled trial 
 
 
Primary outcome:  
1. Change in the average daily GERD symptom severity score from baseline to the last 
week of the study in the expanded vs. standard group. GERD symptom severity is 
based on the sum of scores assessing the severity of daytime heartburn, nighttime 
heartburn, and acid reflux each on a 0-4 point scale (none, mild, moderate, severe, 
very severe; higher scores signify worse symptoms). 
 
Secondary outcomes: 
1. Ratio of the sum of positive correlations over the sum of negative correlations in GSR 
(or HRV) across patient-provider encounters for standard vs. expanded visit types and 
for responders vs. non-responders (those with a 50% or greater improvement in their 
GERD symptom severity).   
2. Absolute change in GSR (or high frequency HRV signal) in patient recordings from 
the beginning of the study visit to the end of the study visit and correlation with 
subsequent change in GERD symptom severity.   
3. Differences in blinded ratings of 2 minute thin slices of study visit videos from the 
beginning to the end of the study in supportive global impressions (e.g., engagement, 
relaxed, patient seems pleased/satisfied) and non-verbal behaviors (e.g., smiling) 
between standard and expanded visit types and correlation with subsequent change in 
GERD symptom severity.  
Study population:  
Men and women age 24-70 with heartburn symptoms 3 or more days per week not 
responsive to proton pump inhibitors or with known functional heartburn. We will enroll 
until we reach 60 completing subjects. 
Study location:  
University of California Davis Medical Center 
Length of subject participation: 8 weeks 
Length of study enrollment: 2 years 
Groups:  
1) Standard visit (n=30), modeled after an empathic, high quality conventional primary 
care visit.  
2) Expanded visit (n=30), modeled after a visit with an integrative medicine provider 
Randomization:  


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The randomization code will be generated by the study statistician as described below 
(sections 4.3 and 9.2). The study will be single-blinded (study providers and the research 
team will know what the subject is receiving but the subject will not). Randomization 
will be stratified based on study provider. We anticipate 5 or 6 providers each seeing 10-
12 subjects (5-6 standard visits, 5-6 expanded visits).   
4. SELECTION AND ENROLLMENT OF PARTICIPANTS  
4.1 
Inclusion Criteria 
Research subjects eligible to receive amitriptyline must meet all of the following 
inclusion criteria to participate in the study: 
• Adults ages 24-70 years old (rationale: population of interest, GERD frequency 
increases with age; amitriptyline is not recommended in older adults and may 
have increased risk of suicidality in adults younger than 24) 
• Functional heartburn (defined as <4% of time with reflux on 24 hour pH 
manometry) symptoms 3 or more days per week with an average daily symptom 
severity of 3 or more on a 7-day baseline symptom diary (see section 6.2.2 for 
description of instrument; rationale: subjects must be symptomatic enough that 
improvement in symptoms is detectable. This threshold is similar to that seen in 
my pilot study64).  
• English language proficiency (rationale: feasibility) 
• Willingness to be videotaped and connected to physiologic monitoring devices 
during the visit (rationale: feasibility/study procedures) 
• Willingness to take amitriptyline daily for 8 weeks following study visit 1 
(rationale: feasibility/study procedures) 
Research subjects eligible to receive omeprazole must meet all of the following 
inclusion criteria to participate in the study: 
• Adults age 24 and older 
• Heartburn symptoms 3 or more days per week with an average daily symptom 
severity of 3 or more on a 7-day baseline symptom diary 
• English language proficiency 
• Willingness to be videotaped and connected to physiologic monitoring devices 
during the visit 
• Willingness to take omeprazole daily for 8 weeks following study visit 1 
4.2 
Exclusion Criteria 
Any candidates eligible to receive an 8-week supply of amitriptyline meeting any of 
the following exclusion criteria at baseline will be excluded from study participation. 
• Diagnosis of Crohn’s disease, systemic sclerosis, known active ulcer disease, 
gastric cancer, or untreated/active Barrett’s esophagitis based on subject self-report 
and/or medical record review (rationale: heartburn symptoms may be due to 
another, more serious medical illness) 


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• Heavy alcohol use (> 6 drinks/week for women and > 13 drinks/week for men) 
based on subject self-report (rationale: can exacerbate heartburn symptoms) 
• Pregnant, attempting to become pregnant, or breast-feeding (rationale: 
feasibility/medical safety - amitriptyline is not recommended in pregnancy or 
breast-feeding and the physiology of heartburn is different in pregnant women).  
• Dementia or significant memory difficulties as determined by the study team and 
medical record review (rationale: feasibility and human subjects concerns) 
• Severe, unstable psychiatric disease based on subject self-report, study team 
determination, and/or medical record review (rationale: feasibility and human 
subjects concerns) 
• Bipolar disorder, concurrent treatment with a SSRI or another antidepressant that 
interacts with tricyclic antidepressants (rationale: medical safety) 
• Prolonged QTc or severe heart disease (rationale: medical safety – amitriptyline 
can prolong cardiac conduction). 
• History of seizure disorder (rationale: medical safety – amitriptyline can lower the 
seizure threshold). 
• Severe liver impairment – e.g., cirrhosis, hepatocellular carcinoma, hepatitis 
(rationale: medical safety, not recommended in patients with hepatic impairment).  
• Currently taking a tricyclic antidepressant, allergy to tricyclic antidepressants, or 
another medical contraindication to taking amitriptyline or related medications 
(rationale: safety and feasibility).  
• Greater than 15 doses of nonsteroidal anti-inflammatory drugs (NSAIDS) within 
the prior 30 days (aspirin ≤ 325 mg daily permitted) or ongoing NSAID use at a 
level deemed likely to interfere with the study (rationale: NSAIDS can exacerbate 
GERD and cause peptic ulcers) 
• Failure to complete the baseline symptom diary for at least 6 of 7 days (rationale: 
feasibility) 
• Change in GERD treatment regimen within the last 2 weeks (subjects may use 
antacids, H2 receptor blockers, and/or proton pump inhibitors as long as they are 
symptomatic on a stable regimen; rationale: feasibility, need a stable symptom 
baseline) 
• Allergy to adhesives (rationale: feasibility/study procedures) 
• Inability to provide informed consent (rationale: human subjects concerns) 
• In the opinion of the investigator, unable to comply with the study protocol or has a 
condition that would likely interfere with the study (rationale: feasibility) 
Any candidates eligible to receive an 8-week supply of omeprazole meeting any of 
the following exclusion criteria at baseline will be excluded from study participation. 


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• Diagnosis of Crohn’s disease, systemic sclerosis, known active ulcer disease, 
gastric cancer, or untreated/active Barrett’s esophagitis based on subject self-report 
and/or medical record review (rationale: heartburn symptoms may be due to 
another, more serious medical illness) 
• Concurrent treatment for H. pylori infection (rationale: treatment for H. pylori may 
resolve heartburn symptoms) 
• Heavy alcohol use (> 6 drinks/week for women and > 13 drinks/week for men) 
based on subject self-report (rationale: can exacerbate heartburn symptoms) 
• Pregnant, attempting to become pregnant, or breast-feeding (rationale: 
feasibility/medical safety - the physiology of heartburn is different in pregnant 
women and omeprazole may not be safe during breast-feeding).  
• Dementia or significant memory difficulties as determined by the study team and 
medical record review (rationale: feasibility and human subjects concerns) 
• Severe, unstable psychiatric disease based on subject self-report, study team 
determination, and/or medical record review (rationale: feasibility and human 
subjects concerns) 
• Greater than 15 doses of nonsteroidal anti-inflammatory drugs (NSAIDS) within 
the prior 30 days (aspirin ≤ 325 mg daily permitted) or ongoing NSAID use at a 
level deemed likely to interfere with the study (rationale: NSAIDS can exacerbate 
GERD and cause peptic ulcers) 
• Currently taking a medication that is contraindicated with omeprazole treatment 
(e.g., acalabrutinib, cefuroxime, dacomitinib, dasatinib, delavirdine, erlotinib, 
infigratinib, pazopanib, pexidartinib, rilpivirine, sotorasib, and strong CYP2C19 
inducers) 
• Allergy to a proton pump inhibitor 
• Failure to complete the baseline symptom diary for at least 6 of 7 days (rationale: 
feasibility) 
• Change in GERD treatment regimen within the last 2 weeks (subjects may use 
antacids, H2 receptor blockers, and/or proton pump inhibitors as long as they are 
symptomatic on a stable regimen; rationale: feasibility, need a stable symptom 
baseline) 
• Allergy to adhesives (rationale: feasibility/study procedures) 
• Inability to provide informed consent (rationale: human subjects concerns) 
• 
In the opinion of the investigator, unable to comply with the study protocol or has a 
condition that would likely interfere with the study (rationale: feasibility) 
4.3 Study Enrollment Procedures  
Patient Recruitment:  


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Initial recruitment efforts will start with the UC Davis Gastroenterology Clinic, and in 
particular, the motility disorders group. We will review scheduled patient visits and 
results from pH studies performed at the Midtown GI Clinic in EPIC. Patients identified 
as having typical GERD symptoms who have not yet tried a PPI or esophageal 
hypersensitivity will be contacted by Dr. Garcia or their UCD gastroenterologist 
regarding their results and this study. The research team will contact the patient about 
the study only if the patient expresses interest and gives permission to the 
gastroenterologist to be contacted by the research team. If Dr. Garcia is unable to reach 
the patient by phone, we will send the patient a letter in the mail or a MyChart message 
to inform them of the study. 
 
Clinicians will also have copies of flyers they can hand to patients and the study 
research coordinator may also meet with some patients directly in the clinic. Study flyers 
may also be posted within the clinic. We may also recruit from primary care clinics. If a 
patient is interested in learning more about the study, they may request additional 
information during their appointment or may call the phone number on the flyer. 
Providers may also obtain verbal permission to give their prospective subjects’ contact 
information to a study staff member who can provide further details about the study. 
This information may be shared with study staff in the form of an Epic patient list.  We 
will also recruit using Study Pages and may use similar electronic recruiting platforms. 
 
We will also recruit patients from the UCD Otolaryngology Reflux Clinic using 
procedures similar to those described above. 
 
Patient Screening:  
Potential subjects will undergo a telephone or in person prescreen by study staff and 
have the opportunity to ask questions about the study (see telephone script). Potential 
subjects will be informed that the study involves taking amitriptyline or omeprazole 
(depending upon their diagnosis and treatment plan with their physician) daily for 8 
weeks. Assuming the potential subject receives care at UC Davis, their medical record 
will be reviewed as part of the eligibility assessment. A standardized form (see attached) 
will be used to ascertain potential eligibility and an electronic screening log will be kept 
to keep track of reasons for ineligibility. Those who are deemed potentially eligible and 
are interested in participating will be sent a 7 day baseline symptom diary (by email or 
via the post office) and scheduled for a baseline visit and 8 week follow-up visit. 
Potential subjects will be mailed a copy of their medication list and asked to update it or 
bring a complete list of medications, vitamins, herbs, and supplements that they are taking 
to the baseline visit. Potential subjects will be called several days after the diary is mailed 
to ensure that they received it and that the instructions for completing the diary are clear. 
One day prior to the scheduled study visit, potential subjects will also be called and 
screened for COVID-19 symptoms/exposure to ensure the safety of the study staff and 
other employees of UD Davis Health. 
 
Baseline Visit and Consent:  
At the first study visit, the baseline symptom diary will be reviewed by a study team 
physician (one of the study investigators) and potential subjects will be rescreened. If 


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they are deemed eligible, they will have an opportunity to review the written informed 
consent document, ask any questions, and will be consented by a study team physician. 
The consent process will include a discussion of the risks and benefits of taking 
amitriptyline or omeprazole (whichever medication is most appropriate to their 
condition). 
To avoid alerting subjects to the fact that we are directly studying the effect of the 
patient-provider relationship on health outcomes (which could influence study 
results69,70), subjects will be told during the consent process that 1) we are studying the 
relationship between their symptoms, their physiology, and their response to 
amitriptyline or omeprazole and 2) we are studying whether physicians mirror patients’ 
physiology as has been suggested by some neuroimaging studies40,71 (to explain why 
providers are being similarly monitored). While it is challenging to study patient-
provider interactions without subjects’ direct knowledge, particularly since both are 
being monitored in this study, we believe that framing the study in this way is the most 
sensible way to proceed and the least likely to substantively affect the study’s results. As 
the standard vs. expanded visit intervention is minimal risk, we believe it meets the federal 
criteria for modification of informed consent72, which allows us to conceal from 
participants that we are studying the patient-provider interaction. 
Individuals who sign the informed consent document and elect to participate in the study 
will be considered enrolled. Only individuals who can provide informed consent will be 
eligible to participate.  
 
 
Provider Recruitment and Screening: 
We will advertise the study to primary care internal medicine and family medicine 
physicians and nurse practitioners via email. We may also recruit providers from the 
division of gastroenterology. We may also present the study at practice group meetings. 
Providers must be willing to adhere to the study protocol and not provide specific 
treatment recommendations (pharmacologic or non-pharmacologic) as this is outside the 
scope of the study. Providers must also be willing to receive a brief training to 
understand how to deliver the standard and expanded visit interventions. 
Provider Consent: 
Participating providers will be consented by the study PI. As study providers will deliver 
both visit interventions, they will be trained in both visit type formats. Providers will be 
notified of which intervention they are delivering immediately before walking into the 
room to conduct the study visit. 
Randomization: 
Once enrolled, subjects will be randomized to receive either the standard visit 
intervention (n=30) or the expanded visit intervention (n=30). They will not know that 
there are two possible visit choices. This aspect will be revealed to subjects during a 
debriefing at the follow-up visit at the end of their participation in the study. We will 
stratify by provider and create permuted block sizes of 2 and 4 with the intent to enroll 
5-6 providers who will each see 10-12 subjects. If a provider cannot commit to this many 


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visits, the study biostatistician may need to adjust the randomization scheme and we will 
consent additional providers. 
 
5. STUDY INTERVENTIONS  
5.1 Interventions, Administration, and Duration  
Subjects will be randomized to receive either a “standard visit” or an “expanded visit” 
with a study provider. The standard visit is based on a high quality, empathic, 
conventional primary care encounter. The expanded visit is based on an integrative 
medicine consultation. Both visits are based on a script of questions and statements to the 
patient/subject (see Appendix E). The standard visit script includes questions about 
GERD history, symptoms, prior evaluation and treatments, and past medical history as 
well as a brief physical exam. The expanded visit script includes the same questions as 
the standard visit script plus additional questions that inquire about the modalities of their 
GI symptoms (e.g., nature of the reflux taste, sensation of heartburn pain and/or 
abdominal fullness, time of day better/worse), details about non-GI symptoms, quality of 
sleep, the effect of the weather on symptoms, food cravings and aversions, menstrual 
flow, fears/phobias, and overall temperament. In this way, the expanded visit tries to 
understand the patient’s/subject’s constitution in a way that many systems of integrative 
medicine attempt to do. To reduce the potential for introducing bias by using the words 
“standard” and “expanded”, the visit templates that the study providers will follow will 
simply refer to the number of questions to be asked on the template (e.g., 6 Question 
Template). 
 
At the end of both the standard and expanded visits, the provider will recommend the 
subject take the study medication and describe how to take it and what to expect. Subjects 
will receive the same scripted advice in both groups. Each subject will receive an 8-week 
supply of amitriptyline or omeprazole with instructions for how to take it (10 mg daily at 
bedtime or 20 mg daily when waking up, respectively).   
 
In our pilot study64 we did not limit the amount of time spent with the study subject. On 
average, the standard visit lasted 18 minutes (range 11-32 minutes) and the expanded 
visit lasted 42 minutes (range 23-74 minutes). The study providers will be instructed to 
maintain equal empathy in both groups (e.g., kind and friendly manner, maintain eye 
contact, active listening and repeating back the patient’s words, expressions of empathy). 
Thus, the main differences between the visits will be the length of time spent with the 
subject and the additional questions that are asked. 
 
Each study provider will participate in an orientation session to learn how to deliver the 
standard and expanded visit interventions. Providers will be explicitly instructed not to 
offer lifestyle treatment advice for GERD to maintain uniformity of the intervention 
across providers. The study PI will review video recordings of the interactions to offer 
feedback to study providers and ensure protocol fidelity. As each study provider finishes 
his/her portion of the study, the PI will interview them to understand their experiences of 
the study, the two visit types, and their views on the doctor-patient relationship.  


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5.2   Handling of Study Interventions  
To minimize potential bias that could affect study staff interactions with subjects, the 
subject will be randomized immediately before the study visit and the study provider 
will receive the appropriate study visit script. At the time of consent, study subjects 
will not be informed about the two different interview types or that part of the study 
involves testing the effect of the doctor-patient interaction on response to treatment. 
Concealment of these aspects of the study protocol is essential to maintaining the 
validity of the study as data suggests that patients’ responses change when they know 
that the doctor-patient interaction is being studied69,70. The study PI, or another study 
team member, will notify subjects at their follow-up study visit, after the exit 
interview, that there were two possible types of physician visits, that this aspect of the 
study was concealed from them initially, and of the rationale for doing so.  A script 
outlining this planned debriefing is present in Appendix F. We believe that this 
intervention is minimal risk and that our plan meets the federal criteria for permitting 
alteration of some elements of informed consent72. 
Subjects will be informed about taking amitriptyline or omeprazole as part of the study 
during the consent process and the study physician will discuss this with them during 
the study visit. Subjects will receive a container with an 8 week supply of the 
medication from a study team member at the end of the study visit.  
5.3   Concomitant Interventions  
5.3.1 Allowed Interventions 
Subjects are permitted to remain on all baseline medications, over-the-counter products, 
and dietary supplements, including those used to treat GERD symptoms during the 
study. We will request that they not change doses of medications used to treat GERD 
symptoms during the 8 weeks that they are enrolled in the study. 
5.3.2 Required Interventions 
Amitriptyline 10 mg or omeprazole 20 mg daily for 8 weeks. 
5.3.3 Prohibited Interventions 
We will ask subjects not to increase their dose of GERD medications, add additional 
GERD medications, or change their GERD treatment regimen (with the exception of 
introducing amitriptyline or omeprazole) during the study. This will be monitored via 
the daily symptom diary and a follow-up visit medication review. 
5.4   Adherence Assessment  
Subject adherence is defined by subjects completing at least 6 out of 7 days of their 
daily symptom diary during the last week of the study period and taking amitriptyline 


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or omeprazole at least 6 out of 7 days during that week. Adherence will be assessed 
when subjects return their symptom diaries at their follow-up visit. For subjects who 
return incomplete symptom diaries, average daily symptom severity for the days 
completed will be calculated. If there is insufficient data to make this calculation, we 
will assume that symptoms are unchanged from baseline. 
 
 
 


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6. STUDY PROCEDURES  
6.1   Schedule of Evaluations for Subjects/Patients 
 
Assessment 
Telephone 
Screening: 
(Day 
-30 to -7) 
Baseline, 
Enrollment, 
Randomization: 
Visit 1 (Day 0) 
Post Intervention: 
Visit 1 
(Day 0) 
Follow-up: Visit 2 
(Day 53 - 60) 
Screening Form 
X 
X 
GERD Daily Symptom Diary 
Reviewed 
X 
X 
Informed Consent Form 
X 
Current Medication List 
X 
X 
Height and weight 
X 
Demographics & Health Behaviors 
X 
Blood Draw (optional) 
X 
X 
GERD-Health Related Quality of Life 
Questionnaire (GERD-HRQL) 
X 
X 
Patient Reported Outcomes 
Measurement Information System 
(PROMIS) GERD 
X 
X 
Gastrointestinal Symptom Rating 
Scale (GSRS) 
X 
X 
Perceived Stress Scale-10 (PSS-10) 
X 
X 
Current Stress Question 
X 
X 
X 
NEO Five Factor Inventory (NEO- 
FFI) 
X 
Randomization 
X 
HRV, respiratory rate, skin 
temperature, and GSR 
X 
Video recording 
X 
Study visit 
X 
Impressions of the Study Physician 
 
X 
Consultation And Relational Empathy 
questionnaire (CARE) 
X 
HEAL Patient-Provider Connection 
X 
Adverse Events 
X 
Debriefing 
X 
 
 
 


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Schedules of Evaluations for Providers  
 
Assessment 
Enrollment 
Prior to each 
subject/patient 
encounter 
After each 
subject/patient 
encounter 
After the last 
study visit 
Informed Consent Form 
X 
Interpersonal Reactivity Index (IRI) 
X 
NEO-FFI 
X 
Demographics 
X 
Intervention Training 
X 
PSS-10 
X 
 
 
Current Stress Question 
X 
 
 
Fatigue Scale 
X 
 
 
Physician Satisfaction Questionnaire 
X 
 
Interview at completion of study 
 
X 
 
 


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6.2  
Description of Evaluations  
6.2.1 Telephone Screening (Day -30 to -7) 
A standardized pre-screening form will be used to assess the potential subject’s 
eligibility for the study.  See Appendix B.  
6.2.2 COVID-19 Screening (Day -1) 
A standardized COVID-19 screening form will be used to assess whether the 
potential subject has symptoms consistent with COVID-19 or exposure to 
someone recently diagnosed with COVID-19, prior to the scheduled study visit. If 
the potential subject is experiencing any symptoms or has had a recent exposure, 
the potential subject will be rescheduled for another time at least 2 weeks later in 
order to ensure everyone’s safety. See Appendix B.3. 
 
6.2.3 Enrollment, Baseline, and Randomization (Visit 1, Day 0) 
Potential subjects will be rescreened using the pre-screen form by a study 
physician. The study physician will also review the baseline symptom dairy to 
ensure that the individual is symptomatic enough to enroll. If the individual is 
eligible to participate in the study, they will be given a copy of the consent form 
to review. 
  
Consenting Procedure and Enrollment  
Written informed consent will be obtained by a study team physician (see 
also section 4.3). The subject will be given adequate time to read the 
consent form, and any questions the subject has will be answered. The 
study team physician will confirm that the subject understands that 
he/she will be connected to physiologic monitors during the visit and 
that the visit will be video recorded. The physician will also discuss the 
risks and benefits of taking amitriptyline or omeprazole. The subject will 
also have the opportunity to choose whether or not to consent to blood 
draws as part of the study which will involve one blood draw at the first 
visit and one blood draw at the second visit. The subject will receive a 
copy of the consent form and the original signed copy will be kept in a 
study binder. If the subject agrees to participate and signs the informed 
consent form, they will be considered “enrolled”. 
Study providers will be consented by the study PI, following a similar 
process, using a different written informed consent form. 
 
Baseline Assessments 
Evaluations for study participants/patients (self-administered questionnaires take 
about 15-25 minutes to complete): 


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• Current medication List – will be pulled from Epic and verified with the 
patient by a study team physician 
• Height and weight – will be obtained by a study team member. 
• Demographics and health behaviors – will access things such as age, 
gender, race/ethnicity, smoking status, alcohol & caffeine use (see 
Appendix D) 
• Blood draw (optional) – 10 mL of blood will be obtained by a trained 
study staff member or phlebotomist. Blood will be processed to obtain 
RNA, DNA, and plasma then frozen at -80oC for later omics analyses.  
• Baseline Symptom Diary – 7-day diary indicating the frequency and 
severity of 9 different GERD and dyspepsia-related symptoms on a 5-
point scale as well as any medications, supplements, or other products 
used to help manage symptoms. The first 3 symptoms (daytime 
heartburn, nighttime heartburn, and acid reflux) will be used to assess 
severity of GERD symptoms. 
• GERD-HRQL – a validated 11 item scale for assessing the impact of 
GERD symptoms on health-related quality of life73. 
• NIH PROMIS GERD scale – a validated 13 item instrument assessing 
frequency and severity of GERD symptoms over a 7-day recall period26. 
• GSRS: The Gastrointestinal Symptom Rating Scale is a validated 15 item 
instrument for measuring the severity of gastrointestinal symptoms74.  It 
contains 5 subscales: abdominal pain, reflux syndrome, diarrhea 
syndrome, indigestion syndrome, and constipation syndrome. 
• Current Stress Question – 1 item self-report measure of current stress 
level on a scale of 0 (no stress) to 10 (extreme stress) 
• Perceived Stress Scale (PSS) – a widely used 10 item measure of 
perceived stress that has been shown to correlate with a variety of 
different health outcomes75.  We have adapted the originally validated 
measure to ask about stress over the past week (7 days), rather than the 
past month, to better fit the timeframe of the study.  We have used this 
timeframe in other studies. 
• NEO Five Factor Inventory (NEO-FFI) – a validated 60 item instrument 
that measured five major dimensions of personality: extraversion, 
neuroticism, agreeableness, conscientiousness, and openness to 
experience76.  Some dimensions have been associated with response to 
enhanced patient-provider interactions in others’ studies77. 
• Physiologic Measures and Video Recording: During the intervention we 
will measure HRV, respiratory rate, skin temperature, and GSR in both 
study patients and study providers. The study visit will also be video 
recorded. During the COVID-19 pandemic, in order to allow us to collect 
physiologic and nonverbal behavior data (e.g., smiles) with the patient 
and physician unmasked, while also complying with institutional and 
state public health guidelines, the patient and doctor will sit in separate 
but adjacent, exam rooms with the door closed and use a video telehealth 
platform (e.g., Zoom, Cisco Meeting) to communicate. We will use the 
recording function to capture video data. 


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Evaluations for study providers: 
• Interpersonal Reactivity Index (IRI) – a validated 28 item self-assessment 
of cognitive and affective components of empathy78. 
• NEO Five Factor Inventory (NEO-FFI) – a validated 60 item instrument 
that measures five major dimensions of personality: extraversion, 
neuroticism, agreeableness, conscientiousness, and openness to experience 
[73]. Some dimensions have been associated with response to enhanced 
patient-provider interactions in others’ studies77. 
• Demographics and practice – will assess things such as age, gender, 
race/ethnicity, and clinical experience (see Appendix D). 
• Current Stress Question – 1 item self-report measure of current stress level 
on a scale of 0 (no stress) to 10 (extreme stress).  Study providers will 
complete this question immediately prior to each study subject visit. 
• Perceived Stress Scale (PSS) – a widely used 10 item measure of 
perceived stress that has been shown to correlate with a variety of different 
health outcomes75. Study providers will complete this questionnaire 
immediately prior to each study subject visit. 
• Fatigue Scale – 1 item self-report measure of the current fatigue level on a 
scale of 0 (no fatigue) to 10 (extreme fatigue).  Study providers will 
complete this question immediately prior to each study subject visit. 
• Physician Satisfaction Questionnaire (PSQ) – 20 item self-report measure 
assessing physician satisfaction with the patient visit.  This measure 
includes a global satisfaction question and 19 items assessing 4 other 
domains: satisfaction with the patient-physician relationship, with the data 
collection process, with the appropriateness of the use of time, and with 
the absence of excessive demands on the part of the patient.  Study 
providers will complete this questionnaire immediately after each study 
visit79.  
Randomization 
Subjects will be randomized on the day of their baseline visit (Visit 1) to receive 
either the standard or expanded visit with the specific provider that they are 
scheduled to see that day. We will stratify randomization by provider so that 
each provider does the same proportion of standard and expanded visits. 
Randomization will occur during or immediately after subjects have completed 
their baseline questionnaires, immediately prior to the study visit.  
6.2.4 Blinding 
This is a single-blinded study. Subjects will be unaware of the possibility for 
two different types of study visits. Study providers and staff will be aware of 
the study intervention delivered, but only immediately prior to the study visit to 
decrease the potential for introducing bias in how study staff interact with 
subjects during recruitment and consent. Subjects will be debriefed at the end of 
the Visit 2 regarding the nature of the study and the intervention that they 


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received. Data will be analyzed in a blinded fashion, also to avoid introducing 
bias. Given the low-risk nature of the study, we do not anticipate a need to 
break the blind while a subject is enrolled. 
 
6.2.5 Post-Intervention Measures (Day 0) 
Immediately following the study physician visit, subjects will be asked to 
complete the following questionnaires: 
• Impressions of the Study Physician questionnaire – a 4 item measure 
assessing the patient’s impression of the study physician including 
overall rating of the physician, satisfaction with the physician, 
willingness to recommend the physician to others, and desire to see the 
physician again.  
• Consultation and Relational Empathy questionnaire (CARE) – a 
validated and commonly used 10 item measure for assessing the quality 
of the patient encounter and perceptions of empathy from the treatment 
provider80.  I used it in my pilot study. 
• HEAL Patient-Provider Connection – a subset of the Healing Encounters 
and Attitudes, a recently validated 7-item measure of the patient-provider 
connection. This is a patient-reported outcome developed as part of a set 
of tools to measure non-specific factors in treatment using the NIH 
PROMIS methodology81. 
• Current Stress Question – 1 item self-report measure of current stress 
level on a scale of 0 (no stress) to 10 (extreme stress) 
 
6.2.6 Telephone Check-in 
Study coordinators will call enrolled subjects who have completed study visit 1 
twice to check in.  The first time will be approximately 1 week after the first 
study visit and the second time 1 week before the second study visit. These 
telephone check-ins will 1) serve as a reminder to participants to complete their 
daily symptom diary, 2) remind participants to take the medication as 
prescribed 3) address any participant questions or concerns, and 4) 
remind/confirm participants’ second study visit appointment. 
Participants who wish to discontinue the study medication and unenroll from the 
study will be directed to speak with the study PI to receive instructions for 
tapering off of the medication if they have not done so already.  
 
6.27 
Completion/Final Evaluation 
We will attempt to schedule subjects’ Visit 2 appointments as close to the 8-
week window as possible but will allow a window of several days (53-60 days). 
Visit 2 will be scheduled simultaneously with Visit 1 to help promote adherence 
to this timeline.  If it is not safe for the subject to come to the lab for study Visit 
2 (due to the COVID-19 pandemic), we will have the subject complete 
questionnaires online and schedule a video or telephone call to obtain adverse 


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event data, determine whether the subject benefited from the medication, and 
conduct the debriefing.   
• Blood draw (optional) – 7.5 mL of blood will be obtained by a trained study 
staff member or phlebotomist. Blood will be processed to obtain RNA and 
plasma then frozen at -80oC for later omics analyses.  
• Current medication List – will be pulled from Epic or the prior visit and 
verified with the subject by a study team physician. 
• GERD-HRQL - a validated 11 item scale for assessing the impact 
of GERD symptoms on health-related quality of life73. 
• NIH PROMIS GERD scale – a validated 13 item instrument assessing 
frequency and severity of GERD symptoms over a 7 day recall period26. 
• GSRS: The Gastrointestinal Symptom Rating Scale is a validated 15 item 
instrument for measuring the severity of gastrointestinal symptoms74. It 
contains 5 subscales: abdominal pain, reflux syndrome, diarrhea syndrome, 
indigestion syndrome, and constipation syndrome. 
• Current Stress Question – 1 item self-report measure of current stress level 
on a scale of 0 (no stress) to 10 (extreme stress). 
• Perceived Stress Scale (PSS) – a widely used 10 item measure of perceived 
stress that has been shown to correlate with a variety of different health 
outcomes75. 
• Adverse events – study staff will ask subjects if they experienced any 
adverse events and ask about any hospital or emergency room visits since 
enrollment. 
• Daily symptom diary – Identical in content to the baseline symptom diary, 
this diary allows subjects to track the frequency and severity of 9 different 
GERD and dyspepsia-related symptoms on a 5 point scale as well as any 
medications, supplements, or other products used to help manage symptoms. 
• Debriefing – a study team member will debrief with each subject 
regarding the two different visit types and the patient-provider 
interaction being studied. See Appendix F for a debriefing script. 
 
If a subject experienced benefit taking amitriptyline or omeprazole, they will be 
offered a 30 day prescription so that they may continue taking the medication 
until they have a chance to follow-up with their PCP or gastroenterologist who 
can continue prescribing and monitoring the medication. If a subject did not 
experience any benefit and/or wishes to stop the medication, they will be 
instructed in how to taper off of it.  
 
 


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7. SAFETY ASSESSMENTS  
Expected risks to subjects are as follows: 
• Study questionnaires: Symptom and behavioral data collection involves virtually no 
risk; however, psychosocial tests or questions about symptom intensity may cause 
minor emotional distress. Because participants are free to stop at any time and will be 
reminded of this throughout the assessment process, the risk of distress is low. In our 
experience, such questionnaires are well-tolerated and complications are extremely 
rare. 
• Discomfort from ECG/GSR leads and physiologic monitoring: Some participants 
may experience minor skin irritation due to the adhesive used to apply leads for 
physiologic monitoring. Subjects with known adhesive allergies will not be eligible 
to participate in the study. Some participants may experience psychological distress 
knowing that their physiology is being monitored. The physiologic monitoring will 
be described in the consent document and care will be taken to minimize such 
distress. Participants will be free to stop at any time. In general, such monitoring is 
well-tolerated. 
• Discomfort from blood draws: some participants may have an aversion to needles, 
blood, and/or the drawing of blood. Blood will be drawn by trained study staff or 
phlebotomists and care will be taken to minimize discomfort to participants. Blood 
draws are generally well-tolerated, although occasionally there may be bruising or 
discomfort at the site. Rarely an infection can occur. The blood draw will be an optional 
component of the study, and if an enrolled subject consents to the blood draw and is 
particularly challenging to draw blood from, we cancel the blood draw and will not 
require a successful blood draw to be a condition of continued enrollment in the study.  
• Videotaping: Some participants may experience psychological distress knowing that they 
are being videotaped. Participants will be free to stop at any time. In general, videotaping 
is generally well-tolerated. 
• Amitriptyline: The most common side effects are dry mouth, sleepiness, and 
constipation.  Less common side effects include dizziness, fatigue, headache, agitation, 
tremor, blurred vision, nausea, insomnia, and sexual dysfunction.  Rare side effects 
include an allergic reaction, changes in heart conduction causing slowing or speeding 
up of the heart rate, serotonin syndrome, and suicidal ideation. We are prescribing low 
doses of this medication and have excluded those most vulnerable to adverse effects 
and so do not anticipate any serious adverse events. If a study subject calls with 
concerns about side effects, they will be directed to speak with a physician on the study 
team to assess their symptoms and determine whether any dose modification or further 
evaluation is needed. If it is deemed that the subject should stop the medication, they 
will be instructed in how to do so. If it is determined that they need further medical 
evaluation, they will be instructed what to do.   
• Omeprazole: The most common side effects are headaches, abdominal pain, diarrhea, 
and nausea. Less common side effects include skin rash, constipation, dizziness, and 
back pain. Rarely someone may develop a hypersensitivity reaction, acute interstitial 
nephritis, lupus, or an enteric infection. Long-term use may increase the risk of 


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fractures, vitamin B12 deficiency, or low magnesium levels. Despite these risks, 
omeprazole is generally well-tolerated and available over-the-counter. If a study 
subject calls with concerns about side effects, they will be directed to speak with a 
physician on the study team to assess their symptoms and determine whether any dose 
modification or further evaluation is needed. If it is deemed that the subject should stop 
the medication, they will be instructed in how to do so. If it is determined that they 
need further medical evaluation, they will be instructed what to do.   
• Severe GERD symptoms: It is possible that subjects may experience a flare in their 
GERD symptoms during the study. If a subject calls with severe GERD symptoms, he 
or she will be directed to speak with a study physician to discuss their symptoms and 
determine the best course of action. In some cases as needed antacids may be 
recommended for refractory symptoms. If this recommendation does not suffice, the 
subject may need to initiate additional medication and possibly be removed from the 
study.  
• Deception: Subjects may experience minor psychological distress at study visit 2 when 
they learn that some information was withheld from them at enrollment. Based upon 
our experience with our prior studies, we feel this is unlikely to happen or to be 
problematic as we have experience conducting such debriefings and subjects generally 
understand why such information was withheld initially. 
 
7.1 
Specification of Safety Parameters 
As amitriptyline is known to cause cardiac conduction delays and lower the seizure 
threshold in some individuals, we will not enroll anyone with known cardiac disease 
or seizure history that would be allocated amitriptyline during the study. We will also 
not enroll anyone with bipolar disorder (to avoid causing mania) or medications that 
could interact with amitriptyline and cause serotonin syndrome that would be 
allocated amitriptyline during the study.  
7.2 
Methods and Timing for Assessing, Recording, and Analyzing Safety 
Parameters 
Subjects will be instructed to call the research team if they have any questions or 
concerns during the study period. A research team member will call subjects 
approximately 1 week into the study period to confirm that they are taking their 
study medication as prescribed and to see if they have any questions or concerns. If 
so, a physician on the study team will reach out to them.  
When subjects return for their follow-up visit, a study team member will inquire 
about any changes to their health or medical visits (including emergency room visits 
or hospitalizations) since their initial study visit. We will ask specifically if they 
experienced any adverse effects from the amitriptyline or omeprazole. If a subject 
reports a new or worsening symptom that is medically concerning (e.g., bright red 
blood per rectum), they will be referred for further evaluation. 


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7.3 
Adverse Events and Serious Adverse Events  
An adverse event (AE) is any unfavorable or unintended diagnosis, symptom, sign, 
syndrome or disease which either occurs during the study (having been absent at 
baseline), or if present at baseline, appears to worsen. 
A serious adverse event (SAE) is any untoward medical occurrence that results in 
death, is life threatening, requires inpatient hospitalization or prolongation of 
existing hospitalization, results in persistent or significant disability/incapacity, or is 
a congenital anomaly. 
During the follow-up visit, the study team member will specifically ask about any new 
or worsening symptoms in the last 8 weeks, unanticipated medical appointments, 
emergency room, or hospital visits. 
In addition, during telephone check-ins, the study research coordinator will record 
any health concerns reported by subjects (not specifically solicited) and report 
these to the study PI. If there are any signs or symptoms of concern or that require 
further clarification, the study PI will contact the subject. 
• Unexpected fatal or life-threatening AEs related to the intervention will be 
reported to the National Center for Complementary and Integrative Health 
(NCCIH) Program Officer within 3 business days of the investigator 
becoming aware of the event and to the study’s Independent Safety 
Monitor(s) and UC Davis IRB within 5 business days of the investigator 
becoming aware of the event. Other serious and unexpected AEs related to 
the intervention will be reported within 5 business days. 
• Anticipated or unrelated SAEs will be handled in a less urgent manner but will 
be reported to the Independent Safety Monitor(s), IRB, and other oversight 
organizations in accordance with their requirements and will be reported to 
NCCIH on an annual basis. 
• All other AEs documented during the course of the trial will be reported to 
NCCIH and the UC Davis IRB on an annual basis by way of inclusion in the 
annual report and in the annual AE summary which will be provided to NCCIH 
and to the Independent Monitors. The Independent Safety Monitor(s) Report 
will state that all AEs have been reviewed (see Data Safety and Monitoring 
Plan). 
 
7.4 
Reporting Procedures 
Study staff and visit intervention providers will be instructed to report all adverse 
events (or potential AEs) to the study PI (Dr. Dossett). Determination of relatedness 
will be made in conjunction with Dr. Henry and/or Dr. Garcia. An electronic log of 
various types of AEs will be kept and updated by study staff. 
 
7.5 
Follow-up for Adverse Events 
AEs will be followed-up by the study PI by phone calls to the subject and/or 


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monitoring of the medical record until they are resolved or considered stable. Formal 
AE follow-up will end with subjects’ follow-up visit unless they have an ongoing 
issue or call to report an event after completing the study. 
 
7.6 
Safety Monitoring  
Please see the separate data safety and monitoring plan for this study, found in 
Appendix G. 
8. INTERVENTION DISCONTINUATION  
Subjects who decline to participate in study procedures (e.g., completion of study 
questionnaires, physiologic monitoring, and/or video recording) will be terminated from the 
study without further follow-up. Any subjects who are disruptive or felt to pose a threat to 
study staff will also be terminated without follow-up. If a subject experiences an adverse 
reaction to amitriptyline or omeprazole and decides to stop taking the medication, or if a study 
physician deems it in the subject’s best interest to stop the medication, the subject will 
continue to be followed for the duration of their initially planned participation (out to 8 
weeks), unless the subject declines to participate further.  
9. STATISTICAL CONSIDERATIONS  
9.1 
General Design Issues  
Design: This is a single-blinded randomized controlled trial in which subjects will 
be randomized in a 1:1 fashion to receive either an expanded or standard visit with 
a healthcare provider about their GERD symptoms and then treated with 
amitriptyline or omeprazole for 8 weeks to determine whether an expanded visit can 
augment the effects of a medication compared to a standard visit.  
Primary hypotheses: 
1. Subjects who receive an expanded visit will have a greater improvement in 
their GERD symptoms after 8 weeks of treatment with amitriptyline or 
omeprazole compared to subjects who receive a standard visit.   
Secondary hypothesis: 
1. Patient-provider dyads in expanded visits will have a greater percentage of 
the total visit time spent in physiologic concordance (measured by either GSR 
or HRV) compared patient-provider dyads in standard visits.   
2. Percentage of visit time with physiologic concordance (in GSR or HRV) will 
be correlated with GERD symptom improvement. 
3. Subjects who experience physiologic changes similar to those elicited by mind-
body techniques (i.e., decreased GSR and increased high frequency HRV) over 
the course of their visit (first several minutes compared to the last several 
minutes of the visit) will demonstrate greater improvements in GERD symptom 
severity than subjects who do not. 


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4. Healthcare providers in expanded visits will demonstrate more patient-
centered non-verbal behaviors (e.g., smiles and gazes) and global impression 
(e.g., engaged, friendly, relaxed) compared to providers in standard visits as 
rated by blinded reviews of thin slices of video excerpts.  
5. Patient and provider smiling at the end of study visits will be significantly 
associated with GERD symptom improvement 8 weeks later. 
 
Primary outcome: 
1. Change in the average daily GERD symptom severity score from baseline to 
the last week of the study in the expanded vs. standard group. GERD 
symptom severity is based on the sum of scores assessing the severity of 
daytime heartburn, nighttime heartburn, and acid reflux each on a 0-4 point 
scale (none, mild, moderate, severe, very severe; higher scores signify 
worse symptoms). 
Secondary outcomes: 
1. Ratio of the sum of positive correlations over the sum of negative correlations in 
GSR (or HRV) across patient-provider encounters for standard vs. expanded visit 
types and for responders vs. non-responders (those with a 50% or greater 
improvement in their GERD symptom severity).   
2. Absolute change in GSR (or high frequency HRV signal) in patient recordings 
from the beginning of the study visit to the end of the study visit and correlation 
with subsequent change in GERD symptom severity.   
3. Differences in blinded ratings of 2 minute thin slices of study visit videos 
from the beginning to the end of the study in supportive global impressions 
(e.g., engagement, relaxed, patient seems pleased/satisfied) and non-verbal 
behaviors (e.g., smiling) between standard and expanded visit types and 
correlation with subsequent change in GERD symptom severity.  
Validity and reliability of outcome measures: 
1. Assessment of physiologic concordance has been described by a number of 
groups and we will be using similar methodology45,82. 
2. GERD symptom severity will be assessed by a daily symptom diary used by a 
number of other groups in medication trials and in our previous study64,83,84. 
The average daily GERD symptom severity is based on the daily sum of scores 
from the first three questions assessing severity of daytime heartburn, 
nighttime heartburn, and acid reflux averaged over a 7 day period. The change 
in GERD symptom severity is calculated by subtracting the average daily 
GERD symptom severity score during the last 7 days of the study from the 
average daily GERD symptom severity score at study enrollment. The other 
GERD symptom questionnaires we are using have also been validated26,73,74. 
3. Social psychologists have developed and validated a variety of coding schemes 
to analyze providers’ verbal and non-verbal behaviors and to link these 
behaviors with patient satisfaction, understanding, trust, rapport, empathy, and a 
variety of related factors9,58–63. We will use a subset of these validated coding 


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schemes. Thin slices have shown high reliability and validity for behaviors such 
as gaze, nods, and smiles85. 
 
9.2 
Sample Size and Randomization 
The combined standard deviation (root mean square error) in my pilot fellowship 
study was 1.564. We are conservatively assuming that this number will likely be larger 
in this study given the greater number of providers involved. Given 30 subjects in 
each group (n=60 total), 80% power, a two-sided 
significance test with alpha = 0.05, the minimal detectable 
difference (MDD) in GERD symptom severity scores 
between the standard and expanded groups given the 
estimated standard deviations (SD) is shown in the adjacent 
table. These MDD values are similar to those found in my 
fellowship study64 and are clinically meaningful86,87. 
 
Treatment Assignment Procedures 
A randomization scheme will be devised before the start of the study by the study 
biostatistician who will retain the code and will be responsible for breaking the blind 
at the end of the study. We do not anticipate a need to break the blind during the 
study because we are not expecting serious adverse events to occur more frequently 
in one visit group than another. Randomization will be stratified by provider, with 
permuted block sizes of 2 and 4 with a goal to have 5-6 providers each see 10-12 
subjects. If a provider cannot commit to this many visits, the study biostatistician 
may need to adjust the randomization scheme and we will consent additional 
providers. 
The study biostatistician will enter the randomization scheme into REDCap and 
subjects will be randomized immediately prior to the study visit intervention.   
If a subject drops out or is unable to complete the study, the statistician may need to 
rebalance the randomization scheme. 
Subjects will be informed of their visit group assignment during the debriefing at the 
end of the second study visit.  
9.3  
Definition of Populations 
For analyses including the intervention group type, we will analyze our data 
according to which visit intervention subjects received (standard or expanded). We 
do not anticipate any discrepancies between what subjects were assigned to receive 
by randomization and what they actually received. Study visit type will be guided 
by a written script that the providers will follow during the visit. The actual 
intervention received will also be verified by reviewing study video recordings. 
The intent to treat analysis will include all randomized subjects who received a 
study visit intervention. The per protocol analysis will include all individuals who 
received a study visit intervention and completed the follow-up questionnaires at 8 
Minimal Detectable 
Difference Between 
Groups 
SD 
MDD 
1.5 
1.10 
2.0 
1.47 
2.5 
1.84 


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weeks. 
9.4 
Interim Analyses and Stopping Rules 
No interim analyses are planned. The study PI will periodically review video 
recordings of visit interventions as the study progresses to offer feedback to the 
study intervention providers and ensure adherence to the protocol.  
If at any point 20% or more of participants have dropped from the study due to 
adverse effects from amitriptyline or omeprazole and/or there is a serious adverse 
event likely due to amitriptyline or omeprazole, the study team will meet with the 
study safety monitor to determine whether any protocol modifications are necessary.   
 
9.5 
Outcomes  
A combination of description statistics, pearson correlations, and general linear models 
(GLM) such as ANCOVA, will be used for analyzing the data.  
 
 


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Assessment 
Time Points Collected 
Analysis Plan 
Section 
Demographics, 
health behaviors, 
height & weight 
Visit 1 
Descriptive statistics 
9.6 
Daily GERD 
Symptom Diary 
Visit 1 & Visit 2 
Primary Outcome – ANCOVA analysis adjusting for 
baseline GERD symptom severity and visit type using 
follow-up GERD symptoms as the outcome.  
9.5.1 
GERD-HRQL 
Visit 1 & Visit 2 
Descriptive statistics and secondary measures of 
GERD symptom severity in ANCOVA analyses. 
9.6 
NIH PROMIS GERD 
GSRS 
Current Stress 
Visit 1 (both before 
& after provider 
visit) 
&Visit 2 
Descriptive statistics and covariate in GLM analyses. 
9.6 
PSS-10 
Visit 1 (before 
provider visit) 
&Visit 2 
GLM to determine whether perceived stress is a 
modifying factor for change in GSR and HRV in the 
context of the visit intervention 
9.6 
FFI 
Visit 1 
GLM to determine whether personality is a 
modifying factor for change in GERD symptoms in 
the context of the visit intervention 
9.6 
GSR & HRV 
Visit 1 
Secondary Outcome – GLM assessing change in 
GERD symptom severity and physiologic concordance 
in patient-provider dyads 
9.5.1 
Video Recording 
Visit 1 
Secondary Outcomes - GLM to compare the 
frequency of supportive provider behaviors between 
the standard and expanded visit groups and responders 
vs. non-responders (those with a 50% or greater 
improvement in GERD symptoms).  
9.5.2 
Impressions of the Study 
Physician  
CARE 
 
Visit 1, 
post- 
intervention 
 
 
GLM to determine whether empathy and the patient-
provider connection modify change in GERD 
symptoms in the context of the visit intervention 
 
 
9.6 
HEAL Patient-
Provider Connection 


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9.5.1 Primary Outcome   
1. Change in the average daily GERD symptom severity score from baseline 
to the last week of the study in the expanded vs. standard group. GERD 
symptom severity is based on the sum of scores assessing the severity of 
daytime heartburn, nighttime heartburn, and acid reflux each on a 0-4 point 
scale (none, mild, moderate, severe, very severe; higher scores signify 
worse symptoms). We will use ANCOVA for the primary analysis, 
adjusting for baseline GERD symptom severity and visit type assignment 
using the 8 week follow-up GERD symptom severity as the outcome. 
Potential moderators that will be assessed in exploratory analyses will 
include gender (both patient and provider), race, visit length, patient stress, 
personality type, and perceived connection with/empathy of the provider.    
 
9.5.2 Secondary Outcomes  
1. To analyze physiologic synchrony in GSR, first, an average slope of the GSR 
will be calculated in the patient and provider recordings in moving 5 second 
windows, offset by 1 second. Next, Pearson correlations with lag zero will be 
calculated over successive 15 second windows between time-locked patient 
and provider GSR slope values. Then, a single session index will be calculated 
from the ratio of the sum of the positive correlations across the entire visit 
divided by the sum of the absolute value of the negative correlations across 
the entire visit. To reduce skew, the natural logarithm of the index will be 
calculated. Thus, an index value of zero reflects equal positive and negative 
correlations, a value greater than zero reflects more concordance in GSR than 
not, while a value less than zero reflects less concordance in the dyad (less 
than 50%)82. These index values will be used in GLM analyses with GERD 
symptom severity and/or correlated with visit type.   
We will also perform similar analyses on the HRV data – comparing variation in 
the beat-to-beat intervals over short segments of time and calculating Pearson 
correlation coefficients for time-locked patient and provider data for these 
intervals. 
2. We will calculate absolute changes in both GSR and also high frequency HRV 
within study subjects from the beginning to the end of the study visit. We will 
assess the Pearson correlation between these changes and reported changes in 
GERD symptom severity. We will also look at absolute levels of GSR and HRV 
at the end of the study visit and compare those values with changes in GERD 
symptom severity in GLM models. As an exploratory analysis, I will test whether 
changes in GSR and HRV are a function of baseline perceived stress and if that 
relationship differs between the standard and expanded visit interventions. 
3. To analyze study visit videos, 2 minute thin slices of each video at three time 
points (beginning, middle, and end of study visits) will be analyzed by trained 
and blinded coders, for the presence of 1) micro-level non-verbal supportive 
behaviors (e.g., gazes, smiles, nods, gestures – measured as absolute number or 


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length of time) as well as 2) macro-level impression ratings of the interaction 
(e.g., engagement, friendliness, relaxed, empathic, reciprocity – measured on a 
1-9 scale). The PI will meet weekly with the coders to review findings and 
resolve areas of disagreement until greater than 70% concordance is achieved 
between coders using Cronbach’s alpha. Each of these variables will be assessed 
in a GLM examining time, visit type, and time x visit type effects. We will also 
calculate the Pearson correlation coefficient for each variable relative to 
improvement in GERD symptoms and construct a GLM examining patient and 
provider smiling as a predictor of improvement in GERD symptoms. Other 
models may also be constructed based on the results of the initial video analyses.  
9.6 
Data Analyses  
We will perform descriptive statistics on the sample demographics similar to our 
prior paper64 including age, gender, race, ethnicity, body mass index (BMI), smoking 
status, and current medication use for GERD symptoms. We will also assess whether 
perceived stress, perceived empathy (both patient and provider), personality type 
(five factor inventory), or demographic factors modify improvement in GERD 
symptoms using generalized linear models. We will use the GERD-HRQL, NIH 
PROMIS GERD, and GSRS as adjunct/corroborating measures of GERD symptom 
severity. Blood samples will be processed and stored at - 80oC for later omics-based 
analyses that will be the subject of a future grant/study. 
 
10. DATA COLLECTION AND QUALITY ASSURANCE 
10.1 Data Collection Forms  
Most questionnaire data will be collected on iPads at the study site using Research 
Electronic Data Capture (REDCap; http://project-redcap.org/) forms. In the event 
that a subject cannot physically return for the second study visit, a link to the 
follow-up questionnaires will be emailed to the subject. Subjects will complete 
GERD symptom dairies either online (REDCap) or in paper format daily. Paper 
data will be doubled entered into a REDCap database by study personal and 
checked for consistency. REDCap is a secure, web-based application developed at 
Vanderbilt University for electronic collection and management of clinical research 
study data and is hosted locally by UC Davis. 
Study staff will maintain an electronic screening file and enrollment log file and 
paper files of consent forms. 
Study participant confidentiality will be maintained by a unique identifier. An 
electronic file linking participants’ personally identifying information and study ID 
will be password protected. All paper data will be stored in a locked filing cabinet. 
Only study affiliated personnel will have access to the study database and 
associated files. Electronic communication with collaborators will only involve 
deidentified information. All published data will be presented in aggregate format 
and deidentified.   


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10.2 Data Management  
All paper symptom diaries will be reviewed in real time with subjects to ensure that 
data can be transferred completely and accurately to electronic form. Such data will 
be double entered and cross checked as described above. All data (questionnaire, 
physiologic, video) will be cleaned by study staff and reviewed every 1-2 months by 
the study PI to ensure accuracy, completeness, and timeliness of subsequent 
analyses.  
10.3 Quality Assurance  
10.3.1 Training 
The study PI will personally train and supervise all research coordinators and interns 
working on the study in collaboration with relevant consultants to ensure that study 
measures are collected appropriately. All research coordinators/interns will have 
completed the appropriate human subjects training programs and may complete 
additional training depending upon the capacity in which they will serve in the 
study. 
10.3.2 Protocol Deviations 
Protocol deviations will be documented and reported to the UC Davis IRB. 
Unapproved major protocol deviations will be reported to the IRB and NCCIH 
within 5 business days of discovery. 
 
Unapproved minor protocol deviations will be reported to the IRB at the time of the 
annual continuing review and to NCCIH annually as well. Should a protocol 
deviation become repetitive and/or problematic, the investigational team may 
consider submitting a protocol amendment to adjust study procedures. 
 
10.3.3 Monitoring 
The study PI will regularly review study questionnaires, HRV and GSR data, video 
recordings, and logs for completeness and quality. Such review will follow each 
subject initially but will occur at least every 1-2 months for the duration of the 
study. 
 
11. PARTICIPANT RIGHTS AND CONFIDENTIALITY  
11.1 Institutional Review Board (IRB) Review  
This protocol and the informed consent documents and any subsequent 
modifications will be reviewed and approved by the UC Davis IRB. 


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11.2 Informed Consent Forms 
Written informed consent will be obtained by a study team physician at the initial 
study visit after reviewing inclusion and exclusion criteria, the participant’s symptom 
diary, and the electronic medical record if the participant is a patient at UC Davis. 
The consent form will describe the purpose of the study, the procedures to be 
followed, and the risks and benefits of participation. Participants will have the 
opportunity to ask questions. A copy will be given to each participant and this fact 
will be documented in the participant’s record. Participants who cannot consent for 
themselves or who are not fluent in English will not be eligible to participate due to 
the nature of the study. 
11.3 Participant Confidentiality  
Study visits will be conducted in a private setting. Whenever possible, 
questionnaire data will be collected electronically using REDCap. REDCap is a 
secure, web-based application developed by Vanderbilt University for electronic 
collection and management of clinical research study data. All electronic data not 
gathered using REDCap (symptoms diaries, physiologic data, video recordings) 
will be stored on a UC Davis shared drive which is backed up regularly to protect 
against data loss and is behind the UC Davis firewall. Any data that cannot be 
collected directly onto a shared drive (i.e., must be saved on a local hard disk 
during data collection) will be collected on an encrypted laptop and transferred to a 
UC Davis-affiliated server shortly after collection. Any paper questionnaire data 
will be stored in a locked filing cabinet. 
Only those researchers involved in the study will have access to electronic and paper 
data. The file linking participants’ personally identifiable information with their 
participant identification number (PID) will be password protected and access will 
be restricted to the fewest number of staff required but will include at least the PI 
and a research coordinator. Electronic access to videos will also be password 
protected. All paper records will be kept in a locked file cabinet. All computer 
entry and analysis will be done using PIDs only. Any data, forms, reports, video 
recordings, and other records that leave the site will be identified only by a PID to 
maintain confidentiality. Digital video files may be stored for up to 12 years but 
may be destroyed sooner. 
Information will not be released without written permission of the participant, 
except as necessary for monitoring by IRB, the NCCIH, and the OHRP. 
 
11.4 Study Discontinuation  
The study may be discontinued at any time by the IRB, the NCCIH, the Office of 
Human Research Protections (OHRP), or other government agencies as part of their 
duties to ensure that research participants are protected. 


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12. POTENTIAL BENEFITS 
12.1 Potential Benefits to Participating Individuals 
Study subjects (“patients”) may experience improvement in their GERD symptoms by 
participating in this study. The placebo response in GERD-related trials may be as 
high as 40% [35] and our prior data suggests that a therapeutic encounter such as the 
expanded visit can result in at least temporary symptom improvement for some 
individuals [61]. In addition, subjects may also experience improvement in their 
GERD symptoms from taking amitriptyline or omeprazole. It is also possible that 
subjects may not experience any direct benefit from participating in this study. 
Subjects will receive $30 and a 2 month supply of amitriptyline or omeprazole for 
participating in the first study visit and $50 for attending the second study visit. 
Participating study providers will also be remunerated for their time ($80.00 per 
visit) and may benefit by learning skills for relating to patients more effectively. 
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36.  Gyawali CP, Fass R. Management of Gastroesophageal Reflux Disease. Gastroenterology. 
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73.  Velanovich V. The development of the GERD-HRQL symptom severity instrument. Dis 
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74.  Revicki DA, Wood M, Wiklund I, Crawley J. Reliability and validity of the Gastrointestinal 
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75.  Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. J Health Soc 
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84.  Chey DW, Huang B, Jackson RL. Lansoprazole and Esomeprazole in Symptomatic GERD. 
Clin Drug Invest. 2003;23(2):69–84.  
85.  Murphy NA, Hall JA, Schmid Mast M, Ruben MA, Frauendorfer D, Blanch-Hartigan D, 
Roter DL, Nguyen L. Reliability and validity of nonverbal thin slices in social interactions. 
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86.  Kahrilas PJ, Miner P, Johanson J, Mao L, Jokubaitis L, Sloan S. Efficacy of rabeprazole in 
the treatment of symptomatic gastroesophageal reflux disease. Dig Dis Sci. 2005 
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2009 Jun 15;29(12):1261–1272. PMID: 19392864 
 
16. LIST OF SUPPLEMENTS/APPENDICES 
 
Appendix A: Recruitment Materials 
A.1 Study flyer for patient subjects 
A.2 Study Flyer/email for healthcare providers 
A.3 Modified Provider Study Flyer 
 
Appendix B: Screening Documents 
B.1 Telephone script for pre-screening (amitriptyline substudy 
B.1.1 Telephone script for pre-screening (omeprazole substudy) 
B.2 Screening form 
B.3 COVID-19 Screening 
 
Appendix C: GERD Daily Symptom Diary 
Appendix D: Study Questionnaires 
Appendix E: Standard and Expanded Visit scripts 
E.1 Standard Visit Script 
E.2 Expanded Visit Script 
 
Appendix F: Debriefing Script 
Appendix G: Data Safety and Monitoring Plan  


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Appendix H: Provider semi-structured exit interview  
 

ICF_001.pdf: 
 
 
 Page 1 of 13 
Do not write below this line. For IRB stamp and version date only. 
Document Revision Date:  April 23, 2019 
HRP-502 Consent Template – General 2018 Common Rule 
Title of research study: Physiology of GERD and Treatment Response 
Investigator: Michelle Dossett, MD, PhD, MPH 
California Experimental Subjects Bill of Rights  
• Someone will explain this research study to you, including: 
o The nature and purpose of the research study. 
o The procedures to be followed. 
o Any drug or device to be used.  
• Any common or important discomforts and risks. 
• Any benefits you might expect. 
• Other procedures, drugs, or devices that might be helpful, and their risks and benefits compared to 
this study. 
o Medical treatment, if any, that is available for complications.  
• Whether or not you take part is up to you. 
• You can choose without force, fraud, deceit, duress, coercion, or undue influence. 
• You can choose not to take part. 
• You can agree to take part now and later change your mind. 
• Whatever you decide it will not be held against you. 
• You can ask all the questions you want before you decide. 
• If you agree to take part, you will be given a signed and dated copy of this document. 
Key Information about This Research Study 
You are invited to participate in a research study. The purpose of this research is to better understand the 
relationship between gastroesophageal reflux disease (GERD) symptoms, physiology (e.g., heart rate 
and the amount of sweat produced by the skin), and response to treatment with amitriptyline. 
Amitriptyline is an FDA-approved medication for depression. In low doses, it can be helpful for treating 
nerve pain. You are invited to be in this study because you have GERD-related symptoms with a 
hypersensitive esophagus. Your participation in this research will involve 2 visits and will last about 2 
months. We expect about 60 people at UC Davis will participate in this research. 
Participation in this study will involve completion of questionnaires, study diaries, meeting with a 
healthcare provider about your symptoms, and taking a medication known as amitriptyline for 2 months. 
There is also an optional blood draw. All research studies involve some risk. These risks are described in 
detail later in this document. There is the possibility that you may benefit from participation in this 
study.  
Here are some reasons you may not want to participate in this research: 
- 
You will be asked to complete a daily diary of your symptoms for a few weeks. 
- 
You will be asked to take a medication, amitriptyline 10 mg, once a day at bedtime for 2 months. 
Some individuals experience side effects with this medication which will be discussed later in 
this consent.  
 
 
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Document Revision Date:  April 23, 2019 
HRP-502 Consent Template – General 2018 Common Rule 
Your participation in this study is voluntary. You do not have to participate in this study if you do not 
want to. There may be other choices available to you. Some other choices may include talking with your 
gastroenterologist or primary care physician about other medications for your symptoms. You will not 
lose any services, benefits, or rights you would normally have if you choose not to participate.  
The remainder of this form contains a more complete description of this study. Please read this 
description carefully. You can ask any questions you need to help decide whether or not to join this 
study.  
Information to help you understand research is online at 
http://www.research.ucdavis.edu/policiescompliance/irb-admin/for-research-participants.  
What if I have Questions?  
The person in charge of this study is Dr. Michelle Dossett. If you have questions or concerns about this 
study, please contact her at 916-734-5367. 
For non-emergency issues you can call the UCDMC Hospital Operator (916-734-2011), tell the 
Operator you are participating in a research study and you wish to talk to the internal medicine resident 
on-call. In the case of an emergency, dial 911 from any phone. 
If you have any questions about your rights as a research subject or have complaints about the research 
study or study team, you may talk to a team member at the Institutional Review Board (IRB) at (916) 
703-9151, hs-irbadmin@ucdavis.edu, or 2921 Stockton Blvd, Suite 1400, Room 1429, Sacramento, CA 
95817. The IRB is a group of people who oversee research.  
How is this research funded? 
This research is being funded by the National Institutes of Health (NIH) also called the sponsor. 
Sponsors may change or be added. 
UC Davis is being paid to conduct this study, but the study doctor and research staff have not received 
any direct income from the sponsor. 
Why is this research being done? 
We are trying to understand if there is an association between GERD symptoms (also known as acid 
reflux or heartburn), a patient’s physiology (their heart rate and the amount of sweat produced by the 
skin measured as skin conductance), and their response to treatment with amitriptyline. Amitriptyline 
was originally designed as an antidepressant medication. However, in much smaller doses, it functions 
as what we call a neuromodulator. It can help to decrease pain signals that are sent to the brain. Data 
suggests that this medication can be helpful in reducing GERD-related symptoms in patients with a 
hypersensitive esophagus. However, we cannot predict who will respond best to this medication.  
 
We hypothesize that certain physiologic markers may help predict response to amitriptyline. To measure 
your physiology, we will examine markers of the stress response, also known as the “fight or flight” 
response. We will ask you to wear a chest strap to measure your heart rate and breathing rate and 2 
electrodes on your fingers to measure your skin conductance (how well your skin conducts tiny amounts 
of electricity based on how much sweat your skin produces). You will only wear the monitors during 
 
 
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Document Revision Date:  April 23, 2019 
HRP-502 Consent Template – General 2018 Common Rule 
your first study visit. We will also ask you to consider providing a sample of blood so that we can 
analyze whether your genes or certain small molecules in the blood help to predict your response to 
treatment. 
 
You may notice that the study healthcare provider (a physician or nurse practitioner) you are meeting 
with is also wearing electrodes on their fingers. There is some data that suggests that healthcare 
providers may mirror patients’ physiology and we are also testing whether this is true.   
 
What happens if I say yes, I want to be in this research? 
If you decide to participate in this research study, the researchers will ask you to  
Study Visit #1 (today) 
• Review your medication list 
• Measure your height and weight 
• Provide a blood sample (optional), approximately 2 teaspoons (10 mL) 
• Complete questionnaires 
• Wear a chest strap to monitor your heart rate and breathing rate and 2 electrodes on your fingers 
to measure skin conductance. You will wear these devices during your visit with the study 
healthcare provider.  
• Meet with a study-affiliated healthcare provider about your GERD symptoms. This visit will be 
video and audio recorded. Only the study team will have access to this data. During the COVID-
19 pandemic, you may meet with the healthcare provider via a telehealth platform instead of in-
person, and your interaction will be video and audio recorded on the telehealth platform. 
• Complete additional questionnaires 
 
Between Study Visits (2 months) 
• Take the study medication (amitriptyline) daily before bed 
• Complete a daily symptom diary for 2 weeks after Visit #1 and again for 2 weeks before Visit #2 
• Study staff will check in with you by phone or email periodically 
 
Study Visit #2 (in 2 months) 
• Return symptom diaries 
• Provide a blood sample (optional), approximately 1.5 teaspoons, (7.5 mL) 
• Complete questionnaires 
• Meet with a study team member 
• Discuss next steps regarding medication (tapering off or continuing) 
How is being in this study different from my regular health care? 
If you take part in this study, the main difference between your regular care and the study is that we will 
give you a 2 month’s supply of medication and ask you to complete symptom diaries and have your 
physiology measured while you meet with our study healthcare providers.  
 
 
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What are my responsibilities if I take part in this research? 
If you take part in this research, you will be responsible for: 
• Attending 2 study visits 
• Taking the study medication daily as prescribed for 2 months 
• Completing study questionnaires and symptom diaries 
 
Do I have to be in this study? What if I say “yes” now and change my mind later? 
No, you do not have to be in this study. Taking part in research is voluntary. You can choose to be in the 
study or not be in the study. If you decide to be in the study, you can choose to leave the study at any 
time. 
If you decide not to take part in the study, or if you choose to leave the study, your choice will not affect 
any treatment relationship you have with healthcare providers at UC Davis Health or any services you 
receive from them. No matter what you decide, and even if your decision changes, there will be no 
penalty to you. You will not lose medical care or any legal rights. 
Please let the researchers know if you choose to leave the study. We will tell you how to leave the study 
safely. 
Instead of being in this research study, your choices may include: no medical treatment, treatment with 
other kinds of medications, or treatment with the medication offered in this study but without the 
physiologic measurements or associated study questionnaires and diary. 
If you decide to leave the research, contact the study team so the investigator can work with you to 
create a safe plan for your withdrawal. This will include instructions for how to taper your medication to 
reduce the risk of side effects.  
If you stop being in the research, data and specimens that have already been collected will not be 
removed from the study database. 
 
What are my other choices if I do not take part in this study? 
You do not have to be in this research study to get care for your GERD. If you decide not to take part in 
this study, you have other choices.  For example: 
You may decide not to get treatment. 
You may choose to take another medication recommended by your physician. 
You may choose to take part in a different study if one is available.  
These options may have risks. Discuss the possible risks and benefits with your study doctor.  
 
We will tell you about any new information that may affect your health, welfare, or choice to stay in the 
research. 
 
 
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Can I be removed from the research without my OK? 
The researchers may take you out of the study, even if you want to continue, if : 
• your health changes and staying on the study is no longer in your best interest; 
• you do not follow the study rules or you no longer meet the requirements to be in the study; or 
• the study is stopped by the sponsor or researchers. 
Is there anyway being in this study could be bad for me? 
There are risks to participating in this research.  The study doctor and study team will monitor you to see 
if you are experiencing any harm related to your participation.  If you experience any pain or discomfort, 
you must inform the study team as soon as possible.   
• Physical Risks  
o Some patients experience side effects when taking amitriptyline.   
▪ The most common side effects are dry mouth (up to 50%) and sleepiness (up 
to 50%).  
▪ Less common side effects include dizziness (2-15%), fatigue (up to 30%), 
constipation (up to 20%), headache (5%), agitation (less than 5%), tremor (up 
to 15%), blurred vision (up to 13%), nausea (up to 20%), insomnia (up to 
10%), and sexual dysfunction (up to 5%).   
▪ Rare side effects include an allergic reaction (less than 2%), changes in heart 
conduction causing slowing or speeding up of the heart rate (less than 1 in 
100), and serotonin syndrome (symptoms include fever, sweating, fast heart 
rate, restless, confusion, and diarrhea; less than 1 in 100).   
o In addition, some participants may experience minor skin irritation from the adhesive 
used to attach the electrodes to your skin (less than 1 in 100).  If you have an allergy 
to adhesives, please let us know.   
o There is also a possibility that your GERD-related symptoms may flare.  If so, please 
call the research team so that a study-affiliated physician can provide 
recommendations.  
o Blood draws may cause a small amount of pain. In addition, you may get a temporary 
bruise or “black and blue mark.” Rarely, people faint when their blood is drawn. Very 
rarely, the vein may become red and swollen or infected. If this happens, the problem 
can be treated. 
• Psychological risks  
o Some people may feel uncomfortable being video recorded.  If you do not wish to be 
video recorded, we will stop your participation in the study.   
o If any of the questions that we ask make you feel uncomfortable, you may refuse to 
answer them or take a break at any time during the study.  
o In rare instances (less than 1 in 1000), people may experience suicidal thoughts while 
taking amitriptyline. We are using a low dose to reduce this risk, but if you 
 
 
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experience such thoughts, please call the research team or go to your local emergency 
room.  
 
As with all research, there is a chance that confidentiality could be compromised. To minimize the risks 
of breach of confidentiality, we will not include any information that directly identifies you on the 
information we collect, and on the data resulting from the research. Instead, we will record a code on the 
information, and we will keep a link between the code and your identity in a different location.  
 
There is a risk that your information could become known to someone not involved in this study.  
What about Birth Control?  
Contraception Requirements for Women  
The study drug may harm a fetus or a breastfeeding baby. If you are pregnant or breastfeeding, you 
cannot take part in this study. If you think you may be pregnant, you should not volunteer for this study. 
If you are able to become pregnant, you must have a pregnancy test before you begin the study. You 
must not get pregnant or breastfeed while you are in this study. If you are a woman who can become 
pregnant, you must take measures to avoid becoming pregnant while you are in this study. The 
following are acceptable measures to avoid becoming pregnant: 
One of the following forms of birth control should be used:  
• Abstinence (not having sexual relations with a person of the opposite sex) 
• Implantable hormone (e.g. Norplant) 
• Intrauterine Device  
• Male partner must have a vasectomy 
• Female sterilization  
• Hormonal injection  
• Oral contraceptives  
 
You must use contraception, at least 1 month before starting study treatment unless you abstain from 
sexual intercourse. You must use contraception during study treatment and for at least 1 week after 
stopping study treatment.  
Will being in this study help me in any way? 
Being in this study may reduce or relieve your GERD symptoms, but we cannot promise this will 
happen. The study treatment might not work at all, or it might have side effects. Even if the study does 
not help you directly, your participation in this study may help other people in the future by helping us 
learn more about GERD and how people respond to amitriptyline. 
 
 
What happens if I benefit from taking amitriptyline? 
If you notice an improvement in your GERD-related symptoms while taking amitriptyline, a study-
affiliated physician can write you a prescription for a 30-day supply of amitriptyline after the study is 
 
 
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over to bridge you until you have a chance to meet with your primary care physician or 
gastroenterologist who can evaluate you and continue prescribing the medication if it is helpful.  
If you do not benefit from the amitriptyline or wish to stop the medication, a study-affiliated physician 
will provide you with instructions for tapering off of the medication.  
Will being in this study cost me anything? 
You will have to pay for basic expenses like any childcare, food, or transportation related to study 
activities.  
 
If you need treatment for side effects while you are on the study, you or your insurance will need to pay 
for this treatment.  
 
For more information about possible costs, please contact the research team. The research team can 
follow UC Davis Uninsured Non-Emergency Estimate Policy (Policy ID 1883) to work with their 
department and Decision Support Services to get you a cost estimate. 
 
Will I be paid or receive anything for being in this study? 
We will pay you $30 for completing Visit 1 and $50 for completing Visit 2, for a total of $80 if you 
complete both study visits. Payment will be provided at the end of the study in the form of check that 
will be mailed to you. If you choose to leave or we take you off the study for any reason, you will 
receive an amount proportional to the number of study visits you completed.  
 
You will also receive a 2 month’s supply of amitriptyline at no cost to you. If you decide to stop 
amitriptyline after the study is over, we will provide you with instructions for how to taper off this 
medication and additional medication, if needed, to complete the taper.  
 
You may be asked for your social security number for payment purposes. It will not be used for any 
other purpose without your permission. 
 
If you receive $600 or more during a calendar year from the University for participating in research, you 
may receive a 1099 for tax reporting purposes.  Reimbursements for travel and other expenses are not 
included in this amount.  
 
What happens if I am injured or get sick because of this study? 
If you are injured or get sick because of this study, medical care is available to you through UC Davis 
Health, your local provider, or emergency services.  
If you are injured as a result of being in this study, the University of California will provide the 
necessary medical treatment. Depending on the circumstances, the costs of the treatment may be covered 
by the University or the study sponsor or may be billed to your insurance company just like other 
medical costs. The University and the study sponsor do not normally provide any other form of 
compensation for injury. For more information about compensation, you may contact the IRB 
Administration at (916) 703-9151 or  HS-IRBAdmin@ucdavis.edu. 
 
 
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What happens to the information collected for the research? 
We will do our best to limit the use or disclosure of your personal information, including information 
from this research study and from your medical records, to people who have a need to review this 
information. We cannot promise complete confidentiality. Some organizations may be required to 
inspect and copy your information including the IRB and other University of California representatives 
responsible for the management or oversight of this study. 
We have strict rules to protect your personal information and protected health information (PHI). We 
will limit who has access to your name, address, phone number, and other information that can identify 
you. We will remove identifiable information from the data we collect about you. After we remove all of 
the identifiers, we will place a code on the information. The code will be linked to your identity but the 
link will be kept in a location that is separate from your study data. We will maintain your study data on 
encrypted computers and access to the information will be limited to only members of the research team 
who need the access to properly conduct the study.  
 
However, we cannot promise complete confidentiality. If you agree to be in this study, Federal or state 
laws may permit or require us to show information to university or government officials and to study 
sponsors responsible for monitoring this study. We may also show your medical records to study 
monitors, auditors, the IRB, and the FDA. These groups are obligated to maintain your confidentiality. 
The following is a list of individuals who may access your records:   
• Members of the research team  
• Offices and committees responsible for the oversight of research 
• Personnel who schedule or perform medical tests or procedures, handle accounting and billing, 
or do other tasks related to this study 
• U.S. Office for Human Research Protections  
• The study sponsor, the National Institutes of Health (NIH) 
 
If you agree to participate in this research study, a signed copy of this consent document will be filed in 
your electronic medical record (EMR) to ensure people caring for you at UC Davis Health will have the 
information they need about this research study when they provide care for you. Placing a copy of this 
consent form in the EMR is intended only to give information to caregivers providing treatment for you 
while you are on this study.  
Federal and state privacy laws give patients the right to access information about their care and 
treatment contained in their medical record. During this study, you may not be able to access certain 
information related to this study in your EMR until the study is complete to ensure that the study 
remains unbiased. If necessary for your care, this information will be provided to you or your physician. 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. 
Law. This website will not include information that can identify you. At most, the website will include a 
summary of the results. You can search this web site at any time. 
 
We will access protected health information (e.g., your medical record) for this study and you will be 
asked to sign a separate form to give your permission. Your medication list will become part of the 
 
 
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research record.  If that happens, your medications may be looked at by the sponsor of this study and 
government agencies or other groups associated with the study.  They may not copy or take your 
personal health information from your medical records unless permitted or required by law. 
Federal law provides additional protections of your medical records and related health information. 
These are described in the UC Davis Health System Notice of Privacy Practices 
(http://www.ucdmc.ucdavis.edu/legal/privacy/) and in an attached document. 
This research is covered by a Certificate of Confidentiality (CoC) from the National Institutes of Health. 
The researchers with this CoC may not disclose or use information, documents, or biospecimens that 
may identify you in any federal, state, or local civil, criminal, administrative, legislative, or other action, 
suit, or proceeding. For example, the information collected in this research cannot be used as evidence in 
a proceeding unless you consent to this use. Information, documents, or biospecimens protected by this 
CoC cannot be disclosed to anyone else who is not connected with the research, except: 
• To a federal agency sponsoring this research when information is needed for auditing or program 
evaluations; 
• To meet the requirements of the U.S. FDA;  
• If a federal, state or local law requires disclosure such as a requirement to report a communicable 
disease; 
• If information about you must be disclosed to prevent serious harm to yourself or others such as 
child abuse, elder abuse or spousal abuse;  
• If you consent to the disclosure, including for your medical treatment, to an insurer or employer 
to obtain information about you; or  
• If it is used for other scientific research, as allowed by federal regulations protecting research 
subjects.  
This CoC also does not prevent you or a family member from voluntarily releasing information about 
yourself and your involvement in this research. 
Will I receive any results from this research?  
No.  Because we are de-identifying the data before we analyze it and not relinking the data to your 
identity we will not be able to share your individual results study results. 
Will information or leftover specimens be used for other research?    
During this research, the study team will obtain information about you. The information will be used for 
this research and may also be used for other research studies here at UC Davis. We may also share the 
information with other institutions for research.  Before using the information for other research, the 
study team will remove information that identifies you so the individuals performing the research will 
not know who the information came from.  We will not ask for additional consent from you to use your 
information for the additional research.   
 
Are there any optional parts of the study? 
 
 
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This part of the consent form is about an additional, optional part of the study that you can choose to 
take part in. Things to know about this optional part of the study: 
• This is optional. You can still take part in the main study even if you say “no” to any or all of 
this optional part of the study. 
• This part of the study will not help you directly. We hope the results from this optional part of 
the study will help us to better predict in the future which patients best respond to the treatment 
being offered in this study.  
• We will not tell you the results of this optional part of the study, and we will not put the results in 
your medical records.  
• Taking part in the optional part of the study will not cost you anything.  
 
The optional part of the study involves having two blood draws, one during each study visit.   
 
We will use your blood samples to conduct genomics and metabolomics analyses to determine whether 
there are certain genes and small molecules in your blood that are activated in response to the study 
treatment and whether this information can help us to predict who will best respond to the treatment.   
 
To maintain your confidentiality, we will freeze your processed blood samples in tubes labeled with 
your unique study ID so that none of your personally identifying information is on the sample.  When 
we report the results of our analyses, we will do so only for the study as an aggregate so that no 
individual genetic data will be reported.   
 
Will genetic research be done as a part of this study? 
Some of the tests we will perform on your blood will be genetic testing, which is done on your DNA. 
DNA, or deoxyribonucleic acid, carries the genetic instructions for the cells that make up your body. 
Genes tell your body how to do things like form your spine, or what color your eyes should be.  
The DNA samples and information sent to other researchers will not include personal information like 
your name or your birthdate. However, even without your name or other identifiers, your genetic 
information is unique to you, like a fingerprint. Scientists expect that over the next few years, 
researchers will be able to look at your genetic information and be able to trace the data back to you (and 
potentially also to your blood relatives).  
There may be other risks related to genetic testing that we don’t know about right now. This is because 
the field of genetics is moving forward very quickly. 
Will My Genetic/Genomic Data Be Shared With Repositories? 
At some point in the future, we will be required to share genetic data with federal repositories. Because 
this research receives funding from the National Institutes of Health (NIH), we will submit your 
genomic information to a public repository approved by NIH. NIH is a national research agency and is 
part of the federal government. The NIH and other central repositories have developed special data 
(information) banks that collect the results of genetic studies, especially when the research looks at all or 
large sections of individual’s genetic code. This is often called whole genome sequencing. Genomic 
information relates to the structure and function of all of the genetic material in the body.  
 
 
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These central banks will store your genetic information and give them to other qualified and approved 
researchers to do more studies. The data that we share with federal repositories will be coded in such a 
way that you would not be able to be identified. We will not share your name, birth date, or any other 
information that could directly identify you. The link to the code would be kept securely at UCD. Even 
so, there is a possibility that when your genomic information is combined with other information 
available to researchers, either now or in the future, they may be able to identify a group you belong to 
(like an ethnic group or a disease population) or, less likely, you personally. NIH prohibits people from 
trying to identify individuals whose genomic information is in an NIH-designated repository.  
We do not think that there will be further risks to your privacy and confidentiality by sharing your 
genetic information with these banks. However, we cannot predict how genetic information will be used 
in the future. The genetic data could be used to study a wide variety of diseases. 
 
Please initial one of the lines below to indicate whether or not you agree to the optional blood draws. 
 
____  Yes, I agree to have my blood drawn at each study visit. 
 
____  No, I DO NOT agree to have my blood drawn at each study visit. 
 
 
Will information or leftover specimens be used for other research?    
We may keep your frozen samples for up to 15 years and may use them for related studies.  Keeping 
data or samples for future research is called “banking.” The banked data and samples will be kept in a 
secure location for use by researchers.  
 
This is what will happen with your banked data and samples:   
• We may use the data and samples in other research projects related to GERD. 
• The data and samples may be shared with other researchers at UC Davis and with researchers 
outside of UC Davis.  
• The banked data and samples will be labeled with a code instead of your name. 
• When we give your data and samples to other investigators for research projects, they will not be 
able to use the code to figure out which data and samples are yours. 
• The research team will maintain a link between your data and samples and your identifiable 
information kept by the study team. 
• You can request to have your data and samples removed from the bank by contacting the 
research team at any time. 
 
 
Please initial one of the lines below to indicate whether or not you agree to the optional data and 
samples banking:  
____   Yes, I agree to have my data and samples banked for future research purposes.  
____   No, I DO NOT agree to have my data and samples banked for future research purposes. 
 
 
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May we contact you by e-mail?  
We are requesting your email address so we can contact you to confirm study appointments and send 
you copies of study diaries. Email is generally not a secure way to communicate about your health, as 
there are many ways for unauthorized users to access email. You should avoid sending sensitive, 
detailed personal information by email. Email should also not be used to convey information of an 
urgent nature. If you need to talk to someone immediately, please contact the study research coordinator 
(you will be given their contact information) or Dr. Michelle Dossett, the lead study investigator). You 
do not have to provide your email address to participate in this study. Please initial one of the lines 
below. 
_____  Yes, may use email to contact me for this study. My email address is: _____________________ 
_____  No, I do not want to be contacted by email.  
 
 
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Signature Block for Capable Adult 
Your signature documents your permission to take part in this research. 
 
 
 
Signature of subject 
 
Date 
 
 
Printed name of subject 
 
 
 
Signature of person obtaining consent 
 
Date 
 
 
 
Printed name of person obtaining consent 
 
 
 
 
 
 
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