GEnetic Counseling Through VIRTUAL Visits in Parkinson's Disease
Phase: NA
Conditions: Parkinson Disease
Sponsor: University of Pennsylvania

 
 
 
 
Protocol 843748– GET VIRTUAL PD 
Page i of 41   
 
 
 
Protocol Template V1.0 (17-June-2020) 
 
 
 
GEnetic counseling Through VIRTUAL visits in 
Parkinson’s Disease (GET VIRTUAL PD) 
Protocol Number: 843748 
National Clinical Trial (NCT) Identified Number: NCT04527146  
Principal Investigator: Thomas F Tropea 
Sponsor: University of Pennsylvania 
Funded by: NONE  
Version Number:  2.0 
21 OCT 2020 
 
STATEMENT OF COMPLIANCE 
The trial will be carried out in accordance with International Conference on Harmonisation Good Clinical 
Practice (ICH GCP) and the following:  
• 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR Part 46, 
21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812)  
 
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are responsible 
for the conduct, management, or oversight of NIH-funded clinical trials have completed Human Subjects 
Protection and ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the Institutional Review Board (IRB) for review and approval.  Approval of both the 
protocol and the consent form must be obtained before any participant is enrolled.  Any amendment to the 
protocol will require review and approval by the IRB before the changes are implemented to the study.  In 
addition, all changes to the consent form will be IRB-approved; a determination will be made regarding 
whether a new consent needs to be obtained from participants who provided consent, using a previously 
approved consent form.  
 

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 2 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
CLINICAL RESEARCH PROTOCOL 
INVESTIGATIONAL 
PRODUCT(S): 
Interactive Multimedia Approach to Genetic 
counseling to INform and educate in Parkinson’s 
Disease (IMAGINE-PD) 
STUDY 
NUMBER(S): 
IRB Number 
843748 
Other Protocol 
Identifiers  
NA 
PROTOCOL(S) TITLE: 
GEnetic counseling Through Virtual visits in 
Parkinson’s Disease (GET VIRTUAL PD) 
REGULATORY SPONSOR: 
None 
FUNDING SPONSOR(S): 
Department of Neurology 
MEDICAL DIRECTOR 
Thomas F Tropea DO 
ORIGINAL PROTOCOL DATE: 
6/17/2020 
VERSION NUMBER: 
V 2.0 
VERSION DATE: 
10/21/2020 
 
 
 
 
 

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 3 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
1 
Study Summary .......................................................................................................... 9 
1.1 
Synopsis ................................................................................................................... 9 
1.2 
Key Roles and Study Governance ...................................................................... 11 
1.3 Schema ........................................................................................................................ 12 
2 
Introduction and RationalE ..................................................................................... 13 
2.1 
Study Rationale .................................................................................................... 13 
2.2 
Background .......................................................................................................... 13 
2.2.1 
Pharmacokinetics, Pharmacodynamics and ToxicologyError! Bookmark not 
defined. 
2.2.2 
Assessment for Potential Study Products Drug-Drug, Drug-Device, 
Device-Device Interactions ................................ Error! Bookmark not defined. 
2.2.3 
Clinical Adverse Event Profile .......................... Error! Bookmark not defined. 
2.2.4 
Dosing Rationale ................................................ Error! Bookmark not defined. 
2.3 
Risk/Benefit Assessment ...................................................................................... 15 
2.3.1 
Known Potential Risks .................................................................................. 15 
2.3.2 
Known Potential Benefits .............................................................................. 15 
2.3.3 
Assessment of Potential Risks and Benefits ................................................. 15 
3 
Study Objectives and Endpoints ............................................................................. 16 
4 
Study Plan ................................................................................................................. 17 
4.1 
Study Design ......................................................................................................... 17 
4.2 
Scientific Rationale for Study Design ................................................................. 17 
4.3 
Justification for Dose ............................................... Error! Bookmark not defined. 
4.4 
End of Study Definition ....................................................................................... 18 
5 
Study Population ....................................................................................................... 19 
5.1 
Inclusion Criteria ................................................................................................. 19 
5.2 
Exclusion Criteria ................................................................................................ 19 
5.3 
Lifestyle Considerations .......................................... Error! Bookmark not defined. 
5.4 
Screen Failures ..................................................................................................... 19 
5.5 
Strategies for Recruitment and Retention ......................................................... 19 
6 
Study Intervention .................................................................................................... 21 
6.1 
Study Intervention(s) Administration ................................................................ 21 
6.1.1 
Study Intervention Description .................................................................... 21 
6.1.2 
Dosing and Administration ............................... Error! Bookmark not defined. 
6.2 
Preparation/Handling/Storage/Accountability ..... Error! Bookmark not defined. 
6.2.1 
Acquisition and accountability ......................... Error! Bookmark not defined. 
6.2.2 
Formulation, Appearance, Packaging, and Labeling ... Error! Bookmark not 
defined. 
6.2.3 
Product Storage and Stability ........................... Error! Bookmark not defined. 
6.2.4 
Preparation ......................................................... Error! Bookmark not defined. 
6.3 
Measures to Minimize Bias: Randomization and Blinding ............................. 22 
6.4 
Study Intervention Compliance .......................................................................... 22 
6.5 
Concomitant Therapy .............................................. Error! Bookmark not defined. 
6.5.1 
Rescue Medicine ................................................. Error! Bookmark not defined. 
 

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 4 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
7 
Study Intervention Discontinuation and Participant 
Discontinuation/Withdrawal ................................................................................... 23 
7.1 
Discontinuation of Study Intervention ............................................................... 23 
7.2 
Participant Discontinuation/Withdrawal from the Study ............................... 23 
7.3 
Lost To Follow-Up ............................................................................................... 23 
8 
Study Assessment and Procedures .......................................................................... 25 
8.1 
Efficacy Assessments ........................................................................................... 25 
8.2 
Safety and Other Assessments ............................................................................ 25 
8.3 
Adverse Events and Serious Adverse Events .................................................... 26 
8.3.1 
Definition of Adverse Events (AE) ............................................................... 26 
8.3.2 
Definition of Serious Adverse Events (SAE) ............................................... 26 
8.3.3 
Classification of an Adverse Event ............................................................... 27 
8.3.4 
Time Period and Frequency for Event Assessment and Follow-Up ......... 27 
8.3.5 
Adverse Event Reporting .............................................................................. 28 
8.3.6 
Serious Adverse Event Reporting ................................................................ 29 
8.3.7 
Reporting Events to Participants ................................................................. 29 
8.3.8 
Events of Special Interest .................................. Error! Bookmark not defined. 
8.3.9 
Reporting of Pregnancy ................................................................................. 29 
8.4 
Unanticipated Problems ...................................................................................... 29 
8.4.1 
Definition of Unanticipated Problems (UP) ................................................. 29 
8.4.2 
Unanticipated Problem Reporting ............................................................... 30 
8.4.3 
Reporting Unanticipated Problems To Participants .................................. 31 
9 
Statistical Considerations ......................................................................................... 31 
9.1 
Statistical Hypotheses .......................................................................................... 31 
9.2 
Sample Size Determination ................................................................................. 31 
9.3 
Populations for Analyses ..................................................................................... 31 
9.4 
Statistical Analyses .............................................................................................. 32 
9.4.1 
General Approach .......................................................................................... 32 
9.4.2 
Analysis of the Primary Efficacy Endpoint(s) ............................................. 32 
9.4.3 
Analysis of the Secondary Endpoint(s) ........................................................ 32 
9.4.4 
Safety Analyses ............................................................................................... 32 
9.4.5 
Baseline Descriptive Statistics ....................................................................... 33 
9.4.6 
Planned Interim Analyses ............................................................................. 33 
9.4.7 
Sub-Group Analyses ...................................................................................... 33 
9.4.8 
Tabulation of Individual Participant Data .................................................. 33 
9.4.9 
Exploratory Analyses ........................................ Error! Bookmark not defined. 
10 Supporting Documentation and Operational Considerations .............................. 33 
10.1 
Regulatory, Ethical, and Study Oversight Considerations .............................. 33 
10.1.1 
Informed Consent Process ............................................................................ 33 
10.1.2 
Study Discontinuation and Closure .............................................................. 34 
10.1.3 
Confidentiality and Privacy .......................................................................... 34 
10.1.4 
Future Use of Stored Specimens and Data .................................................. 35 
10.1.5 
Safety Oversight ............................................................................................. 35 

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 5 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
10.1.6 
Clinical Monitoring ........................................................................................ 35 
10.1.7 
Quality Assurance and Quality Control ...................................................... 36 
10.1.8 
Data Handling and Record Keeping ............................................................ 36 
10.1.9 
Protocol Deviations ........................................................................................ 36 
10.1.10 
Publication and Data Sharing Policy ........................................................... 37 
10.1.11 
Conflict of Interest Policy .............................................................................. 37 
10.2 
Additional Considerations .................................................................................. 37 
10.3 
Protocol Amendment History ............................................................................. 38 
11 References .................................................................................................................. 38 
12 APPENDIX ................................................................................................................ 41 
12.1 
Schedule of Activities (SoA) ................................................................................ 41 
 
 
 
 
 

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 6 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
 
PRINCIPAL INVESTIGATOR SIGNATURE 
 
STUDY 
SPONSOR: 
NA 
STUDY TITLE: 
GET Virtual PD 
STUDY ID 
PROTOCOL 
VERSION 
843748 
v2.0 
I have read the referenced protocol. I agree to conduct the study in accordance to this protocol, in 
compliance with the Declaration of Helsinki, Good Clinical Practices (GCP), and all applicable 
regulatory requirements and guidelines. 
Principal 
Investigator Name  
 
 
Signature 
 
Affiliation: 
 
 
Date 
 
 
 
 
 
 
 

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 7 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
Abbreviations 
AE 
Adverse Event 
ANCOVA 
Analysis of Covariance 
CFR 
Code of Federal Regulations 
CLIA 
Clinical Laboratory Improvement Amendments 
MP 
Monitoring Plan 
COC 
Certificate of Confidentiality 
CONSORT 
Consolidated Standards of Reporting Trials 
CRF 
Case Report Form 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DSMB 
Data Safety Monitoring Board 
DRE 
Disease-Related Event 
EC 
Ethics Committee 
eCRF 
Electronic Case Report Forms 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act of 2007 
FFR 
Federal Financial Report 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
GWAS 
Genome-Wide Association Studies 
HIPAA 
Health Insurance Portability and Accountability Act  
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonization  
ICMJE 
International Committee of Medical Journal Editors 
IDE 
Investigational Device Exemption 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
ISO 
International Organization for Standardization 
ITT 
Intention-To-Treat 

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 8 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
LSMEANS 
Least-Squares Means 
MedDRA 
Medical Dictionary for Regulatory Activities 
MOP 
Manual of Procedures 
MSDS 
Material Safety Data Sheet 
NCT 
National Clinical Trial 
NIH  
National Institutes of Health 
NIH IC 
NIH Institute or Center 
OHRP 
Office for Human Research Protections 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
DSMC 
Data Safety Monitoring Committee 
SoA 
Schedule of Activities 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
UADE 
Unanticipated Adverse Device Effect 
UP 
Unanticipated Problem 
US 
United States 
 
 
 

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 9 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
1 STUDY SUMMARY 
1.1 
Synopsis 
Title:  
GEnetic counseling Through VIRTUAL visits in Parkinson’s Disease  
Short Title: 
GET Virtual PD 
Study 
Description:  
 
This research tests novel approaches to pre-test counseling and post-test 
disclosure of genetic information in people with PD. Participants will be 
randomized to receive different methods of genetic counseling in a factorial 
design. In both pre- and post-test counseling phases, novel genetic 
counseling methods will be compared to telephone genetic counseling to 
demonstrate equivalence. The primary outcomes will be equivalence on 
genetics knowledge and outcomes scales, and the revised impact of events 
scale. The purpose is to develop effective and scalable approaches to 
genetic counseling. This work is crucial for patient safety and will improve 
access to care through novel genetic counseling approaches.  
Objectives:  
The primary objectives of this study are to determine the efficacy of (1) 
an audiovisual, web-based genetic counseling tool called the Interactive, 
Multimedia Approach to Genetic counseling to INform and Educate in 
Parkinson’s Disease (IMAGINE-PD), and (2) disclosure of genetic 
testing results through a real-time, videoconference telegenetics platform 
compared to telephone counseling. 
Primary 
Endpoints:  
Genetics Knowledge Scale 4 weeks after pre-testing counseling, Revised 
Impact of Events Scale 3 months after genetic results disclosure, Genetic 
Counseling Satisfaction Scale (GCSS) immediately after disclosure 
counseling.  
Secondary 
Endpoints: 
GCOS, GDS, STAI, PDQ-39, C-SSRS, MoCA 
Study 
Population: 
N= 320 (80/counseling group) Parkinson’s disease patients seen at the 
University of Pennsylvania Parkinson’s Disease and Movement Disorders 
Center (PDMDC) who are also enrolled in the PDMDC Genetics 
Biobanking Protocol (IRB 830237), aged 21 and over.  
Phase: 
NA 

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 10 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
Description of 
Sites/Facilities  
Single-site 
Enrolling 
Participants: 
UPENN PDMDC  
Description of 
Study 
Intervention: 
For pre-test counseling, an audiovisual, web-based genetic counseling 
tool called the Interactive, Multimedia Approach to Genetic counseling to 
INform and Educate in Parkinson’s Disease (IMAGINE-PD) will be 
compared to telephone counseling. Content, layout, and user testing for 
IMAGINE-PD were developed using the NIH guideline for usability and 
user testing. Expert input was obtained from movement disorders and 
neurogenetics specialists. For post-genetic test results disclosure web-
based video conference genetic counseling will be compared to telephone 
genetic counseling. 
Study Duration: 
36 months 
Participant 
Duration: 
6 months 
 
 
 
 
 

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 11 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
1.2 
Key Roles and Study Governance 
 
Principal Investigator 
Co-Principal Investigator 
Thomas F Tropea, DO, Assistant Professor 
Alice Chen-Plotkin, MD, Associate Professor 
University of Pennsylvania Dept of Neurology  
University of Pennsylvania Dept of Neurology 
330 South 9th St, Philadelphia, PA, 19107 
330 South 9th St, Philadelphia, PA, 19107 
215-829-7731 
215-829-7731 
thomas.tropea@pennmedicine.upenn.edu 
AChen-Pl@pennmedicine.upenn.edu 
 
 

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 12 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
1.3 Schema 
 
Study Schema: Overall Design.  
 
Schedule of Events: 
Time -30-0 days 
Screening (Total n=385) 
• 
Screen potential participants by inclusion and exclusion criteria, call to invite to participate 
• 
MoCA 
Day 0 (Visit 1) 
Randomization (N=80/group) 
• 
IMAGINE-PD/Virtual, IMAGINE-PD/Telephone, Virtual/Virtual, Virtual/Telephone 
Day 0 (Visit 1) 
Baseline assessments/ Study Intervention 
• 
Obtain informed consent, register in REDCap, train on BlueJeans platform, assign GUID  
• 
Pre-Counseling: Demographics, med history, medications, family history, GKS, GDS, STAI, PDQ-39 
• 
Administer pre-test genetic counseling via IMAGINE-PD or virtual visit  
• 
Observe saliva collection for genetic confirmation testing  
• 
Post-Counseling: GCSS 
Day 28-56 (Visit 2) 
Genetics disclosure visit 
• 
Pre-disclosure: GKS (primary outcome)  
• 
Administer Post-test Genetic Counseling via virtual visit or telephone 
• 
Post-disclosure: GCSS (primary outcome) 
Day 90-118 (Visit 3) 
Genetics disclosure follow up (3 months post-disclosure) 
MIND Initiative 
Enrollment
IMAGINE-
PD
Virtual 
Visit
Genetic 
Disclosure
Pre-Test 
Genetic Counseling
Outcome Measurement 
Timepoint (weeks)
Research-
Genetic Testing
Randomization
Confirmation 
Genetic Testing
Virtual visit
Telephone
Virtual visit
Telephone
Consent 
0
4
16
Knowledge, Satisfaction
Distress

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 13 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
• 
IES-R, (Primary outcome), GCOS, GDS, STAI, PDQ-39, C-SSRS 
Day 210-238 (Visit 4) 
End of study assessment (6 months post-disclosure) 
• 
IES-R, GCOS, GDS, STAI, PDQ-39, C-SSRS 
2 INTRODUCTION AND RATIONALE  
2.1 
Study Rationale 
The search for a disease-modifying therapy for Parkinson’s disease (PD) remains ongoing 
despite decades of basic research and unsuccessful clinical trials. Novel treatments targeting 
carriers of pathogenic variants in the glucocerebrosidase (GBA) and LRRK2 genes, the strongest 
genetic risk factors for PD, show great promise. The frequency of GBA and LRRK2 variants is low 
in the general PD population (5-10%, and 1-2%, respectively), and therefore identifying eligible 
patients is a challenge. To achieve this goal, broad genetic testing will become the norm, departing 
from current practice. Broad genetic testing will capture research-eligible patients and in the future 
will identify populations of genetic variant carriers for precision-medicine approaches. However, 
such an expansion in genetic testing raises concerns about the capacity to expand genetic 
counseling, an essential component of clinical-genetic medical care. The current standard-of-care 
model, which utilizes a two-visit, face-to-face counseling model, is limited by access to trained 
genetic counselors to provide pre- and post-genetic testing counseling. Alongside such an 
expansion in genetic testing, it is essential that we develop novel models for safe and effective 
communication of genetic information at scale. Alternative genetic counseling and disclosure 
models involving video or web-based tools are currently being developed or are already in use. 
However, no studies have examined these approaches in the PD population. 
The goals of this research study are to determine the efficacy of (1) an audiovisual, web-based 
genetic counseling method called the Interactive, Multimedia Approach to Genetic counseling to 
INform and Educate in Parkinson’s Disease (IMAGINE-PD), and (2) disclosure of genetic testing 
results through a real-time, videoconference telegenetics platform. 
2.2 
Background 
Clinical Genetics of Parkinson’s disease 
PD was thought to be a sporadic disorder until the late 1990s when genetic mutations 
responsible for the disease were identified in the synuclein gene (SNCA).1 Since that time 
significant progress has been made in understanding the genetics of PD. A number of rare 
mutations have been identified in the genes Parkin, DJ-1, Pink1 and SNCA, which are highly 
penetrant causes of PD.1–4 Additionally, variants with incomplete penetrance have been shown to 
increase risk of PD in certain populations, including in the gene encoding glucocerebrosidase 
(GBA),5 the strongest genetic risk factor for PD. It is estimated that PD is 27% heritable based on 
genetic variants in genome-wide association studies.6  
Genetic testing is rarely pursued in the clinic because genetics do not currently play a role in 
the diagnosis or treatment of patients with PD. However, knowing one’s genetic status is already 
of key importance for clinical research purposes, as therapies targeting carriers of GBA variants 
are being studied in Phase I and II clinical trials. Evidence in PD has demonstrated that patients 

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 14 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
are interested in learning about their genetic data.7,8 Moreover, at the University of Pennsylvania 
(UPenn), my Mentor Alice Chen-Plotkin and I have launched an initiative to approach all PD 
patients seen in our Parkinson’s Disease and Movement Disorders Center (PDMDC) for research 
consent. The first consecutive 376 PD patients approached through this Molecular Integration in 
Neurological Diagnosis (MIND) Initiative were surveyed about their interest in participating in 
genetics research with the potential to learn their own results. Strikingly, 98% indicated interest in 
participating, as well as interest in knowing their genetic results. It is unknown how many will 
agree to perform clinical confirmation testing. Expanded access to genetic testing is also occurring 
on a national level in an effort supported by the Parkinson Foundation called PD Generation, which 
provides genetic counseling and genetic testing to patients with PD. UPenn is a pilot site for this 
clinical trial and I am the site investigator. Although interest is high, practical limitations exist with 
an expansion in genetic testing and counseling in PD. 
 
Novel Genetic Counseling Approaches are Needed in PD 
 The current genetic counseling model relies on a two-visit, face-to-face, pre-test counseling 
and post-test disclosure model to ensure informed consent, understanding, healthy psychosocial 
response, and preventive behaviors.9 There are many practical limitations to this approach 
including lack of access to trained genetic counselors, travel and cost restrictions, and the inability 
to provide effective counseling in the absence of a trained counselor. To address these challenges 
in other diseases, alternative approaches to genetic counseling have been developed for both pre- 
and post-test counseling methods by co-Mentor Angela Bradbury. In the domain of pre-test 
counseling, for instance, the Alzheimer’s Prevention Initiative Generation studies utilized video-
based pre-test genetic counseling to convey information on APOE in Alzheimer’s disease risk.10 
Pre-test counseling via a web-based, interactive tool has also been utilized in the Returning Genetic 
Research Panel Results for Breast Cancer Susceptibility (RESPECT) Study (R01 CA190871: 
Bradbury).11 
 Data from RESPECT studies 
suggest that web-based alternative 
delivery methods of pre- and post-test 
cancer 
genetic 
counseling 
are 
acceptable to many patients and are 
associated with similar outcomes to 
traditional pre-test counseling with a 
genetic provider.  To date, 211 (81%) 
have chosen pre-disclosure education 
by web-based method. Change in 
knowledge, anxiety, cancer-specific 
distress and uncertainty did not differ 
from baseline to post-disclosure 
between 
pre-disclosure 
education 
approaches. Further, the web-based 
approach was not associated with any significant increase in distress or decline in knowledge after 
receipt of result as compared to those who chose pre-disclosure genetic counselor education (See 
Table 1. Change in patient reported outcomes after pre-
disclosure and post-disclosure visits by eHealth pre-disclosure 
delivery as compared to traditional genetic counseling11 
Outcome  
Change from BL to 
post-V1 
Change from BL 
to post-V2 
Knowledge 
NSS 
NSS 
HADS anxiety 
-1.0; p=0.03 
NSS 
HADS depression 
NSS 
-1.1, p=0.002 
IES cancer worry 
NSS 
NSS 
Uncertainty 
-1.4, p=0.04 
NSS 
N=216-246, BL = baseline, V1 = pre-disclosure counseling or 
eHealth alternative (participant choice); V2 = phone disclosure with 
a genetic counselor (GC), NSS = no statistically significant 
difference from those who received pre-test counseling with a GC; 
all p values adjusted for baseline differences between non-
randomized groups 

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 15 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
Table 1).11 The risks and benefits of alternative forms of pre- and post-test genetic counseling in 
PD has not been evaluated. As our knowledge of the genetics of PD expands, so too does our need 
for scalable approaches to counseling that are effective and safe. 
2.3 
Risk/Benefit Assessment 
2.3.1 
Known Potential Risks 
This study provides genetic counseling and testing to all participants. The method of genetic 
counseling varies between randomization groups. There are no known risks that differ between 
forms of genetic counseling including web-based, telephone, or virtual visit methods. Potential 
risks of genetic counseling include anxiety, stress, or discomfort that can arise during genetic 
counseling. Genetic counseling during this study will be conducted by trained genetic counselors 
following clinical guidelines genetic counseling in PD. For participants randomized to 
IMAGINE-PD, participants will have access to a genetic counselor via email for any follow up 
or clarification questions. The risks of genetic testing are relevant to all participants, which 
include the potential for emotional, social, or financial consequences of the testing results. Some 
people may feel angry, sad, anxious, or guilty about the results. There is also a risk of genetic 
discrimination or of re-identification of deidentified genetic results.  
2.3.2 
Known Potential Benefits 
Participating in this study provides genetic counseling and testing for free to participants. This is 
a service that is not always covered by insurance and could cost a significant amount out of 
pocket. Learning ones own genetic testing results may provide relief for some people. 
Additionally, depending on the results of genetic testing, some people may be eligible to 
participate in other clinical trials that aim to slow progression of disease, which some people may 
consider to be a benefit. 
2.3.3 
Assessment of Potential Risks and Benefits 
The risk of causing significant depression, anxiety, or suicidality as a result of genetic counseling 
or testing are very low. Genetic counselors are trained to recognize unsafe conditions and 
changes in affect related to genetic testing. They will follow established clinical pathways and 
will alert the PI with concerns. Additionally, secondary outcomes include scales of depression, 
anxiety, distress, and suicidality, which will be monitored by the study team, overseen by the PI.  

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 16 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
3 STUDY OBJECTIVES AND ENDPOINTS 
Outcomes to be studied include cognitive and affective outcomes, which will be measured via 
questionnaire-based scales (See Table 2). The questionnaires will be administrated electronically 
utilizing REDCap, a secure online data collection tool.  Outcome measures will be collected at 
multiple time points throughout the study; however, the primary outcomes include Genetics 
Knowledge Scale at 4 weeks after pre-testing counseling, Genetics Counseling Satisfaction Scale 
immediately after disclosure counseling, and the Revised Impact of Events Scale 3 months after 
genetic results disclosure. A data monitoring plan will be in place to ensure patient safety.  

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 17 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
4 STUDY PLAN 
4.1 
Study Design 
The proposed study is a single-center, prospective, factorial, non-inferiority, randomized 
cohort design to test the equivalence of telephone genetic counseling model to novel forms of 
pre-test genetic counseling and telegenetic results disclosure in participants with PD carrying a 
GBA or LRRK2 variant (PD+gene+), participants with PD not carrying a GBA or LRRK2 variant 
(PD+gene-), and a group of at-risk LRRK2 or GBA variant carriers without PD (PD-gene+). 
Participants will be recruited from a single center at the University of Pennsylvania Parkinson’s 
Disease and Movement Disorders Center. A separate biobanking protocol, called the Molecular 
Inegration in Neurological Diagnosis MIND Cohort (UPenn IRB # 830237) enrolls subjects with 
PD and collects optional consent for recontact based on eligibility for additional studies. Subjects 
enrolled in MIND would be eligible for GET Virtual PD if they elect to allow recontact. Subjects 
would be recruited to GET Virtual PD after enrolling MIND and after a blood or saliva sample 
has been collected and research-based genetic testing has been performed, but before clinical-
confirmation genetic testing. GET Virtual PD will serve as the follow study to MIND that will 
allow access to genetic counseling and clinical genetic confirmation testing.  
Enrolled participants will be randomized into one of 4 groups based on pre- and post-
genetic test counseling: (1)IMAGINE-PD/Virtual, (2)IMAGINE-PD/Telephone, 
(3)Virtual/Virtual, and (4)Virtual/Telephone, stratified by genetic group. They will receive pre-
test genetic counseling through the Interactive Multimedia Approach to Genetic counseling to 
INform and Educate in Parkinson’s Disease (IMAGINE-PD) website or via virtual visit with a 
genetic counselor. Participants will be asked to complete questionnaires on genetic knowledge, 
cognitive and affective outcomes prior to and 4 weeks after pre-test genetic counseling. All 
participants will then have clinical genetics results disclosure via virtual visit or by telephone 
with a genetic counselor. Patient-reported cognitive and affective outcomes will be measured 6 
weeks and 6 months after genetic results disclosure. The hypothesis is that performance on the 
genetic knowledge scale and the revised impact of events scale will be equivalent between 
counseling groups at 4 weeks after pretest counseling and 6 weeks post disclosure, respectively.  
4.2 
Scientific Rationale for Study Design 
Pretest counseling and post-test disclosure via IMAGINE-PD and telephone will be 
compared to virtual visits using an established telehealth video-conference platform to 
demonstrates equivalence between these remote telegenetic methods. Virtual visits were chosen 
as the comparator group because it is a remote model of genetic counseling that closely mimics 
in-person counseling, and randomized studies have demonstrated high patient satisfaction and 
favorable cognitive and affective outcomes with genetic counseling services delivered via video 
conferencing.12 Although in-person counseling would be considered standard of care, both 
telephone and telegenetic counseling can be conducted remotely and are scalable to capture a 
larger number of people than in-person alone. We also felt that comparing in-person to telehealth 
or telephone would introduce bias because one group would be evaluated in their homes, while 

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 18 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
the other would be conducted in the office, complicating the outcome measures. Finally, given 
the challenges presented by the current SARS CoV-2 Pandemic, remote models of telegenetic 
counseling are in even higher demand, and warrant comparison in a research study in this 
population.  
4.3 
End of Study Definition 
A participant is considered to have completed the study if he or she has completed all phases 
of the study including the last visit or the last scheduled procedure shown in the Schedule of 
Activities (SoA), Appendix Section 12.1. 

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 19 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
5 STUDY POPULATION 
5.1 
Inclusion Criteria 
In order to be able to participate in this study, an individual must meet all of the following 
criteria:  
1. Provision of signed and dated informed consent form 
2. Stated willingness to have clinical confirmation genetic testing, and comply with all study 
procedures and availability for the duration of the study 
3. Male or female, over the age of 21. 
4. English Speaking 
5.2 
Exclusion Criteria 
An individual who meets any of the following criteria will be excluded from participation in this 
study: 
1. Prior genetic counseling and/or clinical testing specifically for Parkinson’s disease 
2. MoCA < 21, or a prior diagnosis of dementia during the screening phase 
5.3 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical trial but are 
not subsequently randomly assigned to the study intervention or entered in the study. A minimal 
set of screen failure information is required to ensure transparent reporting of screen failure 
participants, to meet the Consolidated Standards of Reporting Trials (CONSORT) publishing 
requirements and to respond to queries from regulatory authorities. Minimal information 
includes demography, screen failure details, eligibility criteria, and any serious adverse event 
(SAE). 
5.4 
Strategies for Recruitment and Retention 
Potential participants are those PDMDC PD patients who have enrolled into the MIND study, 
had a blood or saliva sample collected, and have indicated that they would be willing to be 
contacted regarding their potential eligibility for additional studies (see IRB protocol 830237). 
These participants have all had research-based genetic testing, which is not disclosed to them 
because they were not conducted in a CLIA approved lab. A non-clinical research staff member 
will identify subjects with and without PD who carry a GBA or LRRK2 variant from this 
database. A random sample of PD participants not carrying GBA or LRRK2 variants will also be 
identified. These lists will be stripped of any genetic information and provided to the clinical 
research staff. The clinical research staff will initiate contact with potential participants and offer 
for them to be included in this research study. Subjects will be chosen at random from each of 
the lists by choosing 5 subjects per list to contact at a time. If a participant in MIND expressly 
states their interest learning their LRRK2 or GBA status, they will also be invited to participate in 

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 20 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
this study at enrollment in MIND to be included in the next set of 5 subjects per list to be 
contacted.  
We anticipate enrolling 3 subjects per week. Subjects will not be reimbursed for 
participating. To ensure enrollment of historically underrepresented groups, lists will include 
race and sex, and recruitment calls will ensure inclusion of women and non-white participants in 
each recruitment round. No vulnerable populations will be included in this study.  

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 21 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
6 STUDY INTERVENTION 
6.1 
Study Intervention(s) Administration 
6.1.1 
Study Intervention Description 
Virtual telemedicine and telephone genetic pretest and disclosure counseling: The virtual 
visits and telephone visits will be conducted by a certified genetic counselor to provide all 
counseling in accordance with guidelines set forth by the National Society of Genetic 
Counselors. The counseling visit will be conducted in real-time by telephone or via an 
established and secure audiovisual conferencing telemedicine platform (BlueJeans or Penn’s 
approved telemedicine platform) within the PennChart/EPIC electronic medical record 
dashboard.  See Genetic Counseling SOP for additional information.  
 
IMAGINE-PD: The Interactive, Multimedia Approach to Genetic Counseling to INform and 
Educate in Parkinson’s Disease (IMAGINE-PD) is a novel, interactive, web-based, audiovisual, 
self-guided, genetic counseling tool in the development phase through the UPenn Clinical 
Research Computing Unit (CRCU), which has expertise in research computing and development. 
Essential genetic counseling themes, outlined by a senior certified clinical genetics counselor in 
accordance with national guidelines, are presented in a web-based format, utilizing videos, text, 
pictures, and audio. The content was refined using a binned and tiered approach, previously 
described.13 User testing was conducted with PD patients and movement disorders physicians 
according to best practices.14,15 Feedback was incorporated and prototype was created. This 
version underwent usability testing according to NCI usability guidelines,15 and feedback was 
incorporated to create a final version. Participants can interact with IMAGINE-PD at their own 
pace, with the ability to move backward and forward, repeat sections, and have the ability to 
submit questions to the genetic counselor via e-mail. Web analytics will be provided by the 
CRCU. 
6.2 
Genetic testing 
All participants will have completed enrollment in the MIND protocol (UPenn IRB 
protocol #: 830237), and research-based GBA and LRRK2 testing will be completed. A random 
selection of GBA or LRRK2 variant carriers (gene+) and non-carriers (gene-) with PD (PD+), and 
a small sample of GBA or LRRK2 variant carriers (gene+) without PD (PD-) will be selected by 
research staff not involved in clinical data collection. Gene+ groups will have variant 
confirmation testing in a CLIA-approved lab (outside vendor: Fulgent Genetics). Only the 
variant identified in research-based testing will be examined. No further testing will be 
conducted on this sample. For gene- groups research-based GBA and LRRK2 mutation screening 
will be conducted in exactly the same manner as was previously performed. This will be 
conducted in collaboration with Vivianna Van Deerlin, MD PhD at the University of 
Pennsylvania. This is not a CLIA approved test. Participants will be made aware of the 
possibility of having confirmation testing in a CLIA-approved lab or in a non-CLIA lab, 

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 22 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
however, they will only learn which test was conducted at the disclosure visit to prevent partial 
unblinding of their results prior to confirmation testing and genetic counseling visit. 
The results will be communicated to the patient via virtual visit or telephone, based on 
randomization. After the visit the genetic counselor will prepare a summary letter, including 
information specific to the results from that patient. This will be mailed to the patient. See 
Genetic Counseling Guideline for further description.  
6.3 
Assignment of Global Unique Identifier (GUID) 
The GUID is a computer-generated alphanumeric code that is unique to each research 
participant. It protects identifiable information allowing de-identified data to be integrated and 
tracked over time across multiple projects, databases, and biobanks.  
6.4 
Measures to Minimize Bias: Randomization and Blinding 
Subjects will be randomized 1:1:1:1 into each of the 4 factorial-design groups: IMAGINE-
PD/Virtual, IMAGINE-PD/Telephone, Virtual/Virtual, Virtual/Telephone. Participants and 
investigators will be blinded to the genetic testing results (research or clinic confirmation test) 
until the disclosure visit. The non-clinical researcher from the MIND study who will provide 
blinded lists of potential participants will not be involved in study conduct, data collection, 
patient interaction, or have access to any clinical data collected in the GET Virtual PD study.   
6.5 
Study Intervention Compliance 
The CRCU will provide web-analytics demonstrating time spent one each page, total 
time spent on the website, number of clicks, and times visited to the site. This information will 
be used to infer compliance with observing the pre-test counseling via IMAGINE-PD.  

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 23 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
7 STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
 
7.1 
Discontinuation of Study Intervention 
Discontinuation from IMAGINE-PD or virtual/telephone genetic counseling does not mean 
discontinuation from the study, and remaining study procedures should be completed as 
indicated by the study protocol. If a clinically significant finding is identified (including, but not 
limited to changes from baseline) after enrollment, the investigator or qualified designee will 
determine if any change in participant management is needed. Any new clinically relevant 
finding will be reported as an adverse event (AE). 
The data to be collected at the time of study intervention discontinuation will include the 
following: 
• All planned subsequent study interventions 
7.2 
Participant Discontinuation/Withdrawal from the Study 
Participants are free to withdraw from participation in the study at any time upon request. 
An investigator may discontinue or withdraw a participant from the study for the following 
reasons: 
• If any clinical adverse event (AE), or other medical condition or situation occurs such 
that continued participation in the study would not be in the best interest of the 
participant 
The reason for participant discontinuation or withdrawal from the study will be recorded in the 
study log. Subjects who sign the informed consent form and are randomized but do not receive 
the counseling or clinical confirmation testing may be replaced. Subjects who sign the informed 
consent form and are randomized and receive the genetic counseling and/or clinical confirmation 
testing, and subsequently withdraw, or are withdrawn or discontinued from the study, will be 
replaced. 
7.3 
Lost To Follow-Up 
A participant will be considered lost to follow-up if he or she fails to return for 2 scheduled visits 
and is unable to be contacted by the study site staff. 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 24 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
• The site will attempt to contact the participant and reschedule the missed visit within 8 
weeks and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain if the participant wishes to and/or should continue in the study. 
• Before a participant is deemed lost to follow-up, the investigator or designee will make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, 
if necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the participant’s 
medical record or study file.  
• Should the participant continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 25 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
8 STUDY ASSESSMENT AND PROCEDURES 
 
8.1 
Efficacy and Safety Assessments 
Below are assessments to be performed. See Schedule of events for timing of assessments.  
 
Table 2. Summary of outcome measures.  
 
 
Primary Objective/ 
Endpoint 
Description 
Primary 
Outcomes 
Knowledge/Genetics 
Knowledge Scale 
(GKS) 
A genetics knowledge questionnaire will be adapted from questionnaires 
previously administered to PD research studies.7,8 Topics will include general 
and PD-specific genetics knowledge, genetic testing attitudes and beliefs, 
interest in genetic testing and counseling. 
Test-related 
distress/Revised 
Impact of Events 
Scale (IES-R) 
The Revised Impact of Events Scale is a 22 item, 5-point, self-report scale 
measuring the affective impact of routine or acute life stress or trauma over 
the past 7 days. The scale is scored as the mean of non-missing items (88 
points), and in domains of intrusion (32 points), avoidance (32 points), and 
hyperarousal (24).16 The IES has been used to evaluate the impact of 
disclosure of APOE genetic status in The Risk Evaluation and Education for 
Alzheimer’s Disease (REVEAL) longitudinal study.17 
Satisfaction/Genetic 
Counseling 
Satisfaction Scale 
The Genetic Counseling Satisfaction Scale (GCSS) short-form will be 
adapted to be applicable to both in-person and web-based interactions. It is a 
6-item scale that uses a 5-point Likert-type response.18 
Secondary 
Outcomes 
Geriatric Depression 
Scale (GDS) 
The Geriatric Depression Scale (short version) is a 15-item, “Yes/No”, 
validated, self-report measure of depression in older adults.19 
State-Trait Anxiety 
Inventory (STAI) 
The State-Trait Anxiety Inventory is a 20 item, 4-point, well-validated self-
report scale measuring aspects of both state- and trait-anxiety.20 
Parkinson’s Disease 
Questionnaire- 39 
(PDQ-39) 
The PDQ-39 is a disease-specific health status measure that assess multiple 
dimensions of daily living. It is a validated, self-report measure for people 
with PD.21  
Columbia Suicidality 
Severity Rating Scale 
(C-SSRS) 
The Columbia Suicidality Severity Rating Scale is a method to prospectively 
monitor suicidal ideation and behavior, which can be self-administered. The 
Baseline/Screening version will be used at first visit and the Since Last 
Visit version will be used for all subsequent assessments.22 
Genetic Counseling 
Outcome Scale 
(GCOS) 
The Genetic Counseling Outcome Scale (GCOS) is a validated, 24-question 
self-report questionnaire measuring outcomes after genetic counseling.23 
Montreal Cognitive 
Assessment (MoCA) 
The Montreal Cognitive Assessment is a 30-point, well-validated cognitive 
screening tool. Cut-off values have been validated in the PD population.24   

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 26 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
8.2 
Adverse Events and Serious Adverse Events 
8.2.1 
Definition of Adverse Events (AE) 
An adverse event (AE) is any untoward medical occurrence associated with the use of an 
intervention in humans, whether or not considered intervention related. Intercurrent illnesses or 
injuries should be regarded as adverse events. 
A pre-existing condition should be recorded as an adverse event if the frequency, intensity or the 
character of the condition changes. 
8.2.2 
Definition of Serious Adverse Events (SAE)  
Serious Adverse Events (SAE) 
Adverse events are classified as serious or non-serious. A serious adverse event is any AE that, 
in the view of either the investigator or the sponsor, is: 
• fatal 
• life-threatening 
• requires or prolongs hospital stay 
• results in persistent or significant disability or incapacity 
• a congenital anomaly or birth defect 
• an important medical event when the event does not fit the other outcomes, but the event 
may jeopardize the patient and may require medical or surgical intervention (treatment) 
to prevent one of the other outcomes. 
• required intervention to prevent permanent impairment or damage (for devices only) 
Important medical events are those that may not be immediately life threatening but are clearly 
of major clinical significance. They may jeopardize the subject and may require intervention to 
prevent one of the other serious outcomes noted above. For example, drug overdose or abuse, a 
seizure that did not result in in-patient hospitalization, or intensive treatment of bronchospasm in 
an emergency department would typically be considered serious. 

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 27 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
8.2.3 
Classification of an Adverse Event 
8.2.3.1 
Severity of Event 
For adverse events (AEs) not included in the protocol defined grading system, the following 
guidelines will be used to describe severity. 
• Mild – Events require minimal or no treatment and do not interfere with the participant’s 
daily activities.  
• Moderate – Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning. 
Severe – Events interrupt a participant’s usual daily activity and may require systemic drug 
therapy or other treatment. Severe events are usually potentially life-threatening or 
incapacitating. Of note, the term “severe” does not necessarily equate to “serious” 
8.2.3.2 
Relationship to Study Intervention 
All adverse events (AEs) must have their relationship to genetic counseling assessed by the 
clinician who examines and evaluates the participant based on temporal relationship and his/her 
clinical judgment. The degree of certainty about causality will be graded using the categories 
below. In a clinical trial, the study product must always be considered. 
• Related – The AE is known to occur with the genetic counseling, there is a reasonable 
possibility that the genetic counseling caused the AE, or there is a temporal relationship 
between the genetic counseling and event. Reasonable possibility means that there is 
evidence to suggest a causal relationship between the genetic counseling and the AE. 
Not Related – There is not a reasonable possibility that the administration of the genetic 
counseling caused the event, there is no temporal relationship between the genetic counseling 
and event onset, or an alternate etiology has been established 
8.2.3.3 
Expectedness  
The PI will be responsible for determining whether an adverse event (AE) is expected or 
unexpected. An AE will be considered unexpected if the nature, severity, or frequency of the 
event is not consistent with the risk information previously described for genetic counseling. 
8.2.4 
Time Period and Frequency for Event Assessment and Follow-Up 
Safety will be assessed by monitoring and recording potential adverse effects using the CTCAE 
at each study visit. Participants will be monitored by study outcome measures. If CTCAE 

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 28 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
grading does not exist for an adverse event, the severity of mild, moderate, severe, life-
threatening, and death, corresponding to Grades 1-5, will be used whenever possible. 
At each contact with the subject, the investigator will seek information on adverse events by non-
directive questioning and, as appropriate, by examination. Adverse events may also be detected 
when they are volunteered by the subject during the screening process or between visits, or 
through physical examination, laboratory test, or other assessments. Information on all adverse 
events will be recorded in the source documentation. To the extent possible, adverse events will 
be recorded as a diagnosis and symptoms used to make the diagnosis recorded within the 
diagnosis event. 
As much as possible, each adverse event or follow-up information will be evaluated to 
determine: 
1. Severity grade (CTCAE Grade 1-5) 
2. Duration (start and end dates) 
3. Relationship to the study treatment or process – [Reasonable possibility that AE is 
related: No (unrelated/ not suspected) or Yes (a suspected adverse reaction)]. If yes 
(suspected) - is the event possibly, probably or definitely related to the investigational 
treatment? 
4. Expectedness to study treatment or process – [Unexpected – if the event severity and/or 
frequency is not described in the investigator brochure (if applicable) or protocol]. 
5. Action taken with respect to study or investigational treatment or process (none, dose 
adjusted, temporarily interrupted, permanently discontinued, unknown, not applicable) 
6. Whether medication or therapy taken (no concomitant medication/non-drug therapy, 
concomitant medication/non-drug therapy) 
7. Whether the event is serious 
Once an adverse event is detected, it should be followed until its resolution or until it is judged to 
be permanent, and assessment should be made at each visit (or more frequently, if necessary) of 
any changes in severity, the suspected relationship to the study treatment, the interventions 
required to treat it, and the outcome. 
8.2.5 
Adverse Event Reporting 
Reporting Period 
Adverse events will be reported from the time of informed consent until study completion. 

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 29 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
The investigator will report AEs and SAEs to the IRB/EC of record and other local regulatory 
groups per the local requirements. 
8.2.6 
Serious Adverse Event Reporting  
The study clinician will immediately report to the IRB any serious adverse event, whether or not 
considered genetic counseling related, including those listed in the protocol and must include an 
assessment of whether there is a reasonable possibility that genetic counseling caused the event.  
New information regarding the SAE will be reported as it becomes available and in the same 
manner that the initial SAE (i.e. SAE form). All serious adverse events (SAEs) will be followed 
until satisfactory resolution or until the site investigator deems the event to be chronic or the 
participant is stable.  
8.2.7 
Reporting Events to Participants  
For all events, AE and SAE, participants will be informed via mailing at the end of the study. 
Any AE or SAE deemed study intervention related will be included in the informed consent for 
subsequent participants.  
8.2.8 
Reporting of Pregnancy 
Pregnancy, in and of itself, is not regarded as an AE. Genetic counseling may have different 
implications for pregnancy women, we exclude pregnant women at study enrollment, however, 
would not exclude pregnant women from subsequent study visits at the discretion of the study 
participant. 
8.3 
Unanticipated Problems 
8.3.1 
Definition of Unanticipated Problems (UP) 
The Office for Human Research Protections (OHRP) considers unanticipated problems involving 
risks to participants or others to include, in general, any incident, experience, or outcome that 
meets all the following criteria: 
• Unexpected in terms of nature, severity, or frequency given (a) the research procedures 
that are described in the protocol-related documents, such as the Institutional Review 
Board (IRB)-approved research protocol and informed consent document; and (b) the 
characteristics of the participant population being studied; 
• Related or possibly related to participation in the research (“possibly related” means there 
is a reasonable possibility that the incident, experience, or outcome may have been 
caused by the procedures involved in the research); and 

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 30 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
• Suggests that the research places participants or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or 
recognized. 
8.3.2 
Unanticipated Problem Reporting 
Unanticipated problems (UPs) such as: 
• 
Complaint of a participant when the complaint indicates unexpected risks, or the 
complaint cannot be resolved by the research team 
• 
Breach of confidentiality 
• 
Incarceration of a participant when the research was not previously approved under 
Subpart C and the investigator believes it is in the best interest of the subject to remain on 
the study 
• 
Premature closure of a study (e.g., due safety, lack of efficacy, feasibility, financial 
reasons, etc.) 
should be reported by the investigator to the Institutional Review Board (IRB). The UP report 
will include the following information: 
• Protocol identifying information: protocol title and number, PI’s name, and the IRB 
project number; 
• A detailed description of the event, incident, experience, or outcome;  
• An explanation of the basis for determining that the event, incident, experience, or 
outcome represents an UP; 
• A description of any changes to the protocol or other corrective actions that have been 
taken or are proposed in response to the UP. 
To satisfy the requirement for prompt reporting, UPs will be reported using the following 
timeline: 
• UPs that are serious adverse events (SAEs) will be reported as any other SAE. 
• Any other UP will be reported to the IRB within 3 months of the investigator becoming 
aware of the problem. 
All UPs should be reported to appropriate institutional officials (as required by an institution’s 
written reporting procedures), the supporting agency head (or designee), and the Office for 
Human Research Protections (OHRP) within 3 months of the IRB’s receipt of the report of the 
problem from the investigator. 

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 31 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
8.3.3 
Reporting Unanticipated Problems To Participants  
For all UPs participants will be informed via mailing at the end of the study. Any UP deemed 
study intervention related will be included in the informed consent for subsequent participants.  
9 STATISTICAL CONSIDERATIONS 
9.1 
Statistical Hypotheses 
The primary hypotheses are: (1) Scores on the Genetics Knowledge Scale (GKS) will not 
differ between virtual pre-test genetic counseling and IMAGINE-PD methods, and (2) Scores on 
the genetic counseling satisfaction scale and test-related distress scale (IES-R) will not differ 
between telephone and telegenetic results disclosure methods. The primary analyses of 
knowledge will be measured by the GKS at 4 weeks after pre-test counseling; Satisfaction by the 
GCSS score between genetic counseling groups immediately after pretest and disclosure 
counseling; and test-related distress by the IES-R score at 3 months between post disclosure. The 
null hypothesis is that these methods differ.  
Secondary hypotheses include IES-R at 6 months between genetic counseling groups, 
scores on affect, outcomes, and quality of life scales at 3 and 6 months.  
9.2 
Sample Size Determination  
The difference in IES-R between groups after genetic disclosure counseling is used to 
determine sample size. A clinically significant difference in IES-R score is not defined. Sample 
size is determined from previously reported normative data of the IES-R in a community sample 
of N=154 non-PTSD ex-service members, demonstrating a mean of 1.82 (SD=1.05).16 A range of 
equivalence limits, the difference in standard deviation beyond which a significant difference 
would be considered relevant, are demonstrated in Table 3 at alpha = 0.05 and power of 80%.25 A 
sample size of N=80/counseling group (divided between PD+gene+ (45%), PD+gene- (45%), and 
PD-gene+ groups (10%)), with an expected 
attrition of 15-20%, would allow for analysis 
of the primary outcome at a conservative 0.5-
0.75 SD equivalence limit, and allow genetic 
and PD-subgroup analysis.  
9.3 
Populations for Analyses 
Analyses will be conducted for all randomized participants in the Intention-to-Treat (ITT) 
Analysis Dataset, as well as the Per-Protocol Analysis Dataset defined a subset of the 
participants in the full analysis (ITT) set who complied with the protocol sufficiently to ensure 
that these data would be likely to represent the effects of study intervention according to the 
underlying scientific model (e.g., participants who complete the 3-month study visit). 
Equivalence limit (SD) 
Per Group 
Total Sample Size 
0.5 
80 
320 
0.75 
36 
132 
1 
20 
80 
Table 3. Sample Size Estimates. 

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 32 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
9.4 
Statistical Analyses 
9.4.1 
General Approach 
Descriptive statistics will be presented as percentages for binary variables, and as means with 
standard deviations or median with IQR depending on the distribution of the data. For inferential 
tests, the Type I error will be set at 0.05 using two-tailed tests. Covariates will be determined 
based on their significance as independent predictors of outcome, although age and sex will be 
included in all models. Check on normality will be performed through data visualization as well 
as using appropriate statistical tests of normality (eg Shapiro-Wilks test). Transformation of non-
normally distributed continuous variables will be performed, and models will be compared to 
non-transformed models using non-parametric tests.  
9.4.2 
Analysis of the Primary Efficacy Endpoint(s) 
 
The primary endpoint is the score on the IES-R scale, which will be treated as a 
continuous variable. The primary outcome will be difference in IES-R score between the 
counseling groups at 3 months post disclosure. A linear regression model accounting for baseline 
differences in age, sex, and other relevant covariates will be used. Missing data will be handled 
in 2 ways: an analysis of available data, and using an imputed dataset. Imputation will be 
performed via multiple imputation using the MICE (Multivariate Imputation via Chained 
Equations) package. Imputation in this package uses linear and logistic regression to predict 
missing values. MICE assumes missing values are missing at random, and overall missingness 
pattern will be assessed using this package. Results will be reported as means with standard 
errors. Assumptions for each statistical model will be tested. Results will be analyzed using 2 
approaches: data transformation and using nonparametric statistical tests, where necessary. 
Bonferroni correction will be used to correct for multiple-testing comparisons. 
9.4.3 
Analysis of the Secondary Endpoint(s) 
 
All secondary outcome variables will be treated as continuous variables. The hypotheses will 
be difference between counseling method groups at all study timepoints.  A linear regression 
model accounting for baseline differences in age, sex, and other relevant covariates will be used. 
Missing data will be handled in 2 ways: an analysis of available data, and using an imputed 
dataset. Results will be reported as means with standard errors. Assumptions for each statistical 
model will be tested. Results will be analyzed using 2 approaches: data transformation and using 
nonparametric statistical tests, where necessary. Bonferroni correction will be used to correct for 
multiple-testing comparisons.  
9.4.4 
Safety Analyses 
No statistical analysis will be performed on safety endpoints. The Columbia Suicidality 
Rating Scale will be monitored at each visit. Any concerning result will trigger appropriate 
referral for mental health counseling or medical care.  

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 33 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
 
9.4.5 
Baseline Descriptive Statistics 
Counseling groups will be compared on baseline characteristics, including MoCA, Age, 
Sex, Disease Duration, vitals, and all secondary endpoint measurements. Parametric or non-
parametric tests will be used to compare means or frequencies within groups.  
9.4.6 
Planned Interim Analyses  
NA 
9.4.7 
Sub-Group Analyses 
All Primary and Secondary endpoints will be compared using age and sex as covariates in 
each multivariate model. PD and Gene groups will also be compared.  
9.4.8 
Tabulation of Individual Participant Data 
NA 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1 
Regulatory, Ethical, and Study Oversight Considerations 
10.1.1 
Informed Consent Process 
10.1.1.1 
Consent/Assent and Other Informational Documents Provided To Participants 
 
Consent forms describing in detail the study intervention, study procedures, and risks are 
given to the participant in electronic form and documentation of informed consent is required 
prior to starting intervention/administering study intervention via electronic consent.  
10.1.1.2 
Consent Procedures and Documentation 
Informed consent is a process that is initiated prior to the individual’s agreeing to 
participate in the study and continues throughout the individual’s study participation. Consent 
forms will be Institutional Review Board (IRB)-approved and the participant will be asked to 
read and review the document. The investigator will explain the research study to the participant 
and answer any questions that may arise. A verbal explanation will be provided in terms suited to 
the participant’s comprehension of the purposes, procedures, and potential risks of the study and 
of their rights as research participants.  Participants will have the opportunity to carefully review 
the written consent form and ask questions prior to signing. The participants should have the 
opportunity to discuss the study with their family or surrogates or think about it prior to agreeing 
to participate. The participant will sign the informed consent document prior to any procedures 

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 34 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
being done specifically for the study. Participants must be informed that participation is 
voluntary and that they may withdraw from the study at any time, without prejudice. A copy of 
the informed consent document will be given to the participants for their records. The informed 
consent process will be conducted and documented in the source document (including the date), 
and the form signed, before the participant undergoes any study-specific procedures. The rights 
and welfare of the participants will be protected by emphasizing to them that the quality of their 
medical care will not be adversely affected if they decline to participate in this study. 
10.1.2 
Study Discontinuation and Closure 
 
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause.  Written notification, documenting the reason for study suspension or 
termination, will be provided by the suspending or terminating party to study participants.  If the 
study is prematurely terminated or suspended, the Principal Investigator (PI) will promptly 
inform study participants, the Institutional Review Board (IRB), and sponsor and will provide 
the reason(s) for the termination or suspension.  Study participants will be contacted, as 
applicable, and be informed of changes to study visit schedule. 
  
Circumstances that may warrant termination or suspension include, but are not limited to: 
• Determination of unexpected, significant, or unacceptable risk to participants 
• Demonstration of efficacy that would warrant stopping    
• Insufficient compliance to protocol requirements 
• Data that are not sufficiently complete and/or evaluable 
• Determination that the primary endpoint has been met 
• Determination of futility 
 
Study may resume once concerns about safety, protocol compliance, and data quality are 
addressed. 
10.1.3 
Confidentiality and Privacy 
 
Participant confidentiality and privacy is strictly held in trust by the participating 
investigators, their staff, and the sponsor(s) and their interventions. This confidentiality is 
extended to cover testing of biological samples and genetic tests in addition to the clinical 
information relating to participants. Therefore, the study protocol, documentation, data, and all 
other information generated will be held in strict confidence. No information concerning the 
study or the data will be released to any unauthorized third party without prior written approval 
of the sponsor.  
 
All research activities will be conducted in as private a setting as possible. 
 
Representatives of the Institutional Review Board (IRB) or regulatory agencies may inspect all 
documents and records required to be maintained by the investigator, including but not limited 

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 35 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
to, medical records (office, clinic, or hospital) and pharmacy records for the participants in this 
study. The clinical study site will permit access to such records. 
 
The study participant’s contact information will be securely stored at each clinical site for 
internal use during the study. At the end of the study, all records will continue to be kept in a 
secure location for as long a period as dictated by the reviewing IRB or Institutional policies. 
 
Study participant research data, which is for purposes of statistical analysis and scientific 
reporting, will be kept in REDCap and transmitted to a local, secure database.  
 
For participants who have clinical testing at Fulgent Genetics, their information including their 
name, date of birth, and genetic status will be shared with Fulgent and may be stored in the 
internal laboratory database during and after the conclusion of the study. This follows the 
standard-of-care for clinical genetic testing. After the study, Fulgent Genetics will not release 
information without the participant’s express written consent, as specified by HIPAA guidelines 
and CLIA certification guidelines. 
10.1.4 
Future Use of Stored Specimens and Data  
Fulgent Genetics may store the sample and data in an internal laboratory database as is the 
standard-of-care for clinical genetic testing. Fulgent Genetics will not perform additional 
analyses of the data without the express written consent of the participant and/or their physician. 
Fulgent Genetics may perform additional studies on the specimen collected for medical research 
and/or education, after it is anonymized, unless the participant contacts the lab directly to refuse 
and withdraw this consent. 
10.1.5 
Safety Oversight 
 
Safety oversight will be under the direction of a Safety Monitor (SM) composed of an 
individual with the appropriate expertise, including movement disorders neurology or 
neurogenetics. The ISM should be independent from the study conduct and free of conflict of 
interest, or measures should be in place to minimize perceived conflict of interest.  The SM will 
receive reports of safety data in the event of an AD or SAE.  
10.1.6 
Clinical Monitoring 
Clinical site monitoring is conducted to ensure that the rights and well-being of trial 
participants are protected, that the reported trial data are accurate, complete, and verifiable, and 
that the conduct of the trial is in compliance with the currently approved protocol/amendment(s), 
with International Conference on Harmonisation Good Clinical Practice (ICH GCP), and with 
applicable regulatory requirement(s). 
• The PI and Co-PI will conduct monitoring, on a yearly basis through a targeted review of 
certain data. 

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 36 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
10.1.7 
Quality Assurance and Quality Control 
 
Quality control (QC) procedures will be implemented beginning with the data entry 
system and data QC checks that will be run on the database will be generated. Any missing data 
or data anomalies will be analyzed by the Investigator. 
10.1.8 
Data Handling and Record Keeping  
10.1.8.1 
Data Collection and Management Responsibilities  
 
Data collection is the responsibility of the clinical trial staff under the supervision of the 
site investigator. The investigator is responsible for ensuring the accuracy, completeness, 
legibility, and timeliness of the data reported. 
 
All source documents should be completed in a neat, legible manner to ensure accurate 
interpretation of data. Data will be recorded in the electronic case report form (eCRF) derived 
from source documents.  
 
Clinical data (including adverse events (AEs), concomitant medications, and expected 
adverse events) and clinical laboratory data will be entered into REDCAP, a 21 CFR Part 11-
compliant data capture system. The data system includes password protection and internal 
quality checks, such as automatic range checks, to identify data that appear inconsistent, 
incomplete, or inaccurate. Clinical data will be entered directly into REDCap. 
 
Genetic data will be recorded in REDCAP for the study, and externally in the Fulgent 
Genetics internal laboratory database. The participants’ data will be stored at Fulgent with the 
same management guidelines used for standard-of-care in clinical genetic testing. 
10.1.8.2 
Study Records Retention  
 
Study documents should be retained for a minimum of 2 years after the formal 
discontinuation of clinical development of the study intervention. These documents should be 
retained for a longer period, however, if required by local regulations.  
10.1.9 
Protocol Deviations 
 
A protocol deviation is any noncompliance with the clinical trial protocol, International 
Conference on Harmonisation Good Clinical Practice (ICH GCP), or protocol requirements. The 
noncompliance may be either on the part of the participant, the investigator, or the study site 
staff. As a result of deviations, corrective actions are to be developed by the site and 
implemented promptly.  
 
These practices are consistent with ICH GCP:  

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 37 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
• 
4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3  
• 
5.1 Quality Assurance and Quality Control, section 5.1.1  
• 
5.20 Noncompliance, sections 5.20.1, and 5.20.2.  
 
It is the responsibility of the site investigator to use continuous vigilance to identify and report 
deviations within 10 working days of identification of the protocol deviation.  All deviations 
must be addressed in study source documents, reported to IRB, per their policies.  The site 
investigator is responsible for knowing and adhering to the reviewing IRB requirements. 
10.1.10 
Publication and Data Sharing Policy 
 
This study will be conducted in accordance with the following publication and data 
sharing policies and regulations: 
 
National Institutes of Health (NIH) Public Access Policy, which ensures that the public has 
access to the published results of NIH funded research. It requires scientists to submit final peer-
reviewed journal manuscripts that arise from NIH funds to the digital archive PubMed Central 
upon acceptance for publication. 
 
This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of 
NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results 
Information Submission rule. As such, this trial will be registered at ClinicalTrials.gov, and 
results information from this trial will be submitted to ClinicalTrials.gov. In addition, every 
attempt will be made to publish results in peer-reviewed journals.  Data from this study may be 
requested from other researchers up to 10 years after the completion of the primary endpoint by 
contacting the Investigator 
 
In addition, this study will comply with the NIH Genomic Data Sharing Policy, which applies to 
all NIH-funded research that generates large-scale human or non-human genomic data, as well as 
the use of these data for subsequent research. Large-scale data include genome-wide association 
studies (GWAS), single nucleotide polymorphisms (SNP) arrays, and genome sequence, 
transcriptomic, epigenomic, and gene expression data. 
10.1.11 
Conflict of Interest Policy 
 
The independence of this study from any actual or perceived influence, such as by the 
pharmaceutical industry, is critical.  Therefore, any actual conflict of interest of persons who 
have a role in the design, conduct, analysis, publication, or any aspect of this trial will be 
disclosed and managed. Furthermore, persons who have a perceived conflict of interest will be 
required to have such conflicts managed in a way that is appropriate to their participation in the 
design and conduct of this trial.  The study leadership has established policies and procedures for 
all study group members to disclose all conflicts of interest and will establish a mechanism for 
the management of all reported dualities of interest. 

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 38 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
10.2 
Additional Considerations 
NA 
10.3 
Protocol Amendment History 
Version 
Date 
Description of Change  
Brief Rationale 
1.0 
6/15/2020 
Initial Protocol 
 
2.0 
10/7/2020 
Updated protocol with Fulgent Genetics 
sample labeling 
After samples are received at 
MIND, the ones going to Fulgent 
will be re-labeled. Fulgent Genetics 
will receive participants’ name & 
date of birth with their saliva 
samples. Fulgent will perform the 
clinical confirmation testing and 
will have access to the participants’ 
identifiable, labeled genetic results 
as well as their genetic information 
in their database. This is the 
standard-of-care in clinical genetic 
testing.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
11 REFERENCES 
1. 
Polymeropoulos, M. H. et al. Mutation in the alpha-synuclein gene identified in families 
with Parkinson’s disease. Science 276, 2045–7 (1997). 
2. 
Kitada, T. et al. Mutations in the parkin gene cause autosomal recessive juvenile 
parkinsonism. Nature 392, 605–8 (1998). 

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 39 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
3. 
Valente, E. M. et al. Localization of a novel locus for autosomal recessive early-onset 
parkinsonism, PARK6, on human chromosome 1p35-p36. Am. J. Hum. Genet. 68, 895–
900 (2001). 
4. 
Bonifati, V. et al. DJ-1( PARK7), a novel gene for autosomal recessive, early onset 
parkinsonism. Neurol. Sci. 24, 159–160 (2003). 
5. 
Aharon-Peretz, J., Rosenbaum, H. & Gershoni-Baruch, R. Mutations in the 
Glucocerebrosidase Gene and Parkinson’s Disease in Ashkenazi Jews. N. Engl. J. Med. 
351, 1972–1977 (2004). 
6. 
Keller, M. F. et al. Using genome-wide complex trait analysis to quantify ‘missing 
heritability’ in Parkinson’s disease. Hum. Mol. Genet. (2012). doi:10.1093/hmg/dds335 
7. 
Falcone, D. C., Wood, E. M. C., Xie, S. X., Siderowf, A. & Van Deerlin, V. M. Genetic 
testing and Parkinson disease: Assessment of patient knowledge, attitudes, and interest. J. 
Genet. Couns. (2011). doi:10.1007/s10897-011-9362-0 
8. 
Gupte, M. et al. Interest in Genetic Testing in Ashkenazi Jewish Parkinson’s Disease 
Patients and Their Unaffected Relatives. J. Genet. Couns. (2015). doi:10.1007/s10897-
014-9756-x 
9. 
Robson, M. E. et al. American society of clinical oncology policy statement update: 
Genetic and genomic testing for cancer susceptibility. J. Clin. Oncol. (2015). 
doi:10.1200/JCO.2015.63.0996 
10. 
Bradbury, A. R. et al. The Alzheimer’s prevention initiative: Genetic testing, disclosure, 
and counseling strategies. Alzheimer’s Dement. (2015). doi:10.1016/j.jalz.2015.07.233 
11. 
Bradbury, A. R. et al. Interest in and outcomes with web-based education for return of 
genetic research results for inherited susceptibility to breast cancer. Am. Soc. Clin. Oncol. 
Annu. Meet. [abstract]. (2018). 
12. 
Bradbury, A. et al. Utilizing remote real-time videoconferencing to expand access to 
cancer genetic services in community practices: A multicenter feasibility study. J. Med. 
Internet Res. (2016). doi:10.2196/jmir.4564 
13. 
Bradbury, A. R. et al. Development of a tiered and binned genetic counseling model for 
informed consent in the era of multiplex testing for cancer susceptibility. Genet. Med. 
(2015). doi:10.1038/gim.2014.134 
14. 
Fleisher, L. et al. Using health communication best practices to develop a web-based 
provider-patient communication aid: The CONNECTTM study. Patient Educ. Couns. 
(2008). doi:10.1016/j.pec.2008.02.017 

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 40 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
15. 
U.S. Department of Health and Human Services, Research-Based Web Design & 
Usability Guidelines. Available at: 
http://www.usability.gov/guidelines/guidelines_book.pdf.  
16. 
Creamer, M., Bell, R. & Failla, S. Psychometric properties of the Impact of Event Scale - 
Revised. Behav. Res. Ther. (2003). doi:10.1016/j.brat.2003.07.010 
17. 
Christensen, K. D. et al. A randomized controlled trial of disclosing genetic risk 
information for Alzheimer disease via telephone. Genet. Med. (2018). 
doi:10.1038/gim.2017.103 
18. 
DeMarco, T. A., Peshkin, B. N., Mars, B. D. & Tercyak, K. P. Patient satisfaction with 
cancer genetic counseling: A psychometric analysis of the genetic counseling satisfaction 
scale. J. Genet. Couns. (2004). doi:10.1023/B:JOGC.0000035523.96133.bc 
19. 
Sheikh, J. I. & Yesavage, J. A. Geriatric Depression Scale (GDS): Recent evidence and 
development of a shorter version. Clin. Gerontol. (1986). doi:10.1300/J018v05n01 
20. 
Spielberger, C. D. Manual for the State-Trait Anxiety Inventory (STAI Form Y). 
Consulting Psychologists Palo Alto (1983). doi:10.1002/9780470479216.corpsy0943 
21. 
Peto, V., Jenkinson, C., Fitzpatrick, R. & Greenhall, R. The development and validation of 
a short measure of functioning and well being for individuals with Parkinson’s disease. 
Qual. Life Res. (1995). doi:10.1007/BF02260863 
22. 
Posner, K. et al. The Columbia-suicide severity rating scale: Initial validity and internal 
consistency findings from three multisite studies with adolescents and adults. Am. J. 
Psychiatry (2011). doi:10.1176/appi.ajp.2011.10111704 
23. 
Mcallister, M., Wood, A., Dunn, G., Shiloh, S. & Todd, C. The Genetic Counseling 
Outcome Scale: A new patient-reported outcome measure for clinical genetics services. 
Clin. Genet. (2011). doi:10.1111/j.1399-0004.2011.01636.x 
24. 
Dalrymple-alford, J. C. The MoCA Well-suited screen for cognitive impairment in 
Parkinson disease The MoCA Well-suited screen for cognitive impairment in Parkinson 
disease. 1717–1725 (2010). doi:10.1212/WNL.0b013e3181fc29c9 
25. 
Julious, S. A. Sample sizes for clinical trials with Normal data. Stat. Med. (2004). 
doi:10.1002/sim.1783 
 

 
 
Protocol 843748–  
GET VIRTUAL PD 
 
IMAGINE-PD 
Page 41 of 41 
 
Confidential and Proprietary Information of University of Pennsylvania Dept of Neurology 
12 APPENDIX  
12.1 
 Schedule of Activities (SoA) 
Procedures 
Screening 
Day -30 to 0 
Study Visit 1, 
Day 0 
Study Visit 2 
Day 28-56  
Study Visit 3 
Day 90-118 
Study Visit 4 
Day 210-238 
Informed consent 
 
X 
 
 
 
Demographics 
 
X 
 
 
 
Medical Historya 
 
X 
 
 
 
MoCA 
X 
 
 
 
 
Randomization 
 
X 
 
 
 
Pretest Counseling (Virtual or IMAGINE-PD) 
 
X 
 
 
 
Genetic Testing 
 
Xd 
 
 
 
Genetic Test Disclosure (Virtual or 
Telephone) 
 
 
X 
 
 
Genetics Knowledge Scale  
 
Xb 
Xb 
 
X 
Geriatric Depression Scale 
 
X 
 
X 
X 
State Trait Anxiety Scale 
 
X 
 
X 
X 
Parkinson’s Disease Questionnaire-39 
 
X 
 
X 
X 
Genetic Counseling Satisfaction Scale 
 
Xc 
Xc 
 
 
Revised Impact of Events 
 
 
 
X 
X 
Columbia Suicidality Rating Scale 
 
 
 
X 
X 
Genetic Counseling Outcomes Scale 
 
 
 
X 
X 
Complete Case Report Forms (CRFs) 
x 
X 
X 
X 
X 
Adverse Events Review  
 
X 
X 
X 
X 
aMedical History includes medical history, medication review, family history review.  bPrior to genetic 
counseling. cAfter genetic counseling. dFulgent or in-house testing for confirmation tests. 
 
13 ATTACHMENTS 
13.1 
Genetic Counseling Checklists 
13.2 
Saliva Collection Standard Operating Procedure 
13.3 
Telephone Outreach Script 
13.4 
Case Report Forms 
13.5 
Genetic Counseling Letters 
 
END OF DOCUMENT