Exploring the Effects of Corticosteroids on the Human Hippocampus Using Neurocognitive Testing and High Resolution Neuroimaging
Phase: PHASE4
Conditions: Hydrocortisone, Depression, Healthy Volunteers
Sponsor: University of Texas Southwestern Medical Center

STUDY PROTOCOL AND STATISTICAL ANALYSIS PLAN 
 
 
 
Official title:  Exploring the Effects of Corticosteroids on the 
Human Hippocampus using Neuroimaging 
 
NCT number: NCT03896659 
IRB Approved date: June 14, 2023 

Form A 
IRB # 
STU  2018-0360 
 
STU2018-0360, Brown, FormA-Protocol, Mod_21, 06-14-23 
 
1 
vMar2018 
PROTOCOL FORM / RESEARCH DESCRIPTION 
 
If an item does not apply to your research project, indicate that the question is "not applicable” – do not leave sections blank 
 
Click once on the highlighted entry in each box to provide your response.  Click the item number/letter or word, if hyperlinked, 
for detailed instructions for that question.  If your response requires inserting a table, picture, etc, you may need to first delete the 
box that surrounds the answer and then insert your table or other special document. 
 
 
1.  Purpose and objectives.           List the purpose and objectives: 
 
This study will, for the first time in humans, examine the effects of cortisol on specific hippocampal subfields using state-of-the art 
multimodal high-resolution neuroimaging methods. This research study is translational in nature and will advance our 
understanding of the effects of stress and cortisol on the brain. This is a non-treatment study. The researchers are interested in 
whether hydrocortisone (medication form of a stress hormone cortisol) influences the brains of depressed vs. non-depressed 
people differently. The researchers are also interested in whether there are differences in the effects of hydrocortisone between 
males and females. The study has both mechanistic and clinical aims. The aims are as follows: 
 
Mechanistic Aim 1: Determine the effect of cortisol on task-driven hippocampal activation using, for the first time, high-resolution 
(1.5 mm isotropic) functional MRI of hippocampal subfields (i.e., DG/CA3, CA1, subiculum). 
Mechanistic Aim 2: Determine the effect of cortisol on hippocampal subfield volume using high-resolution structural MRI. 
Mechanistic Aim 3: Assess changes in hippocampal metabolites NAA, Glu, Cho and mI with cortisol using 1HMRS 
(spectroscopy). 
Clinical Aim 4: Determine the effect of cortisol on declarative and visuospatial memory. 
Clinical Aim 5: Determine whether sex, stress, early life adversity, age, physical activity, GCR number or sensitivity, or changes 
in sleep during cortisol administration, predict hippocampal CS response, as assessed by memory testing and multimodal 
neuroimaging.  
Exploratory Aim 6: Explore the effects of cortisol on resting state functional connectivity using whole brain connectomic mapping.  
Exploratory Aim 7: Explore the impact of depressive symptoms on memory and hippocampal structure, activation, connectivity 
and 1HMRS outcomes in response to hydrocortisone administration. 
 
 
2.  Background. 
• 
Describe past experimental and/or clinical findings leading to the formulation of your study.   
• 
For research involving investigational drugs, describe the previously conducted animal and human studies.   
• 
For research that involves FDA approved drugs or devices, describe the FDA approved uses of this drug/device in 
relation to your protocol.   
• 
Attach a copy of the approved labeling as a product package insert or from the Physician’s Desk Reference.   
You may reference sponsor’s full protocol or grant application (section number and/or title) or if none, ensure background 
includes references. 
 
Please respond to all components of this item, or clearly indicate which components are not applicable. 
 
a. 
Background 
See grant application uploaded in section 4.1.3d of the Smartform. The background information can be found in Section 3 
(Research Strategy, pages 68-69).  
 
b. 
Current practice 
N/A 
 
 
3.  Study Design.  
Describe the study design (e.g., single/double blind, parallel, crossover, etc.)  Consider inserting a scheme to visually present the 
study design. 
The study involves a double-blind, placebo-controlled, crossover design of hydrocortisone in depressed and non-depressed 
(healthy controls) participants. Within each group (depressed and non-depressed), participants will be randomized to receive 

Form A 
IRB # 
STU  2018-0360 
 
STU2018-0360, Brown, FormA-Protocol, Mod_21, 06-14-23 
 
2 
vMar2018 
hydrocortisone or placebo for 3 days, followed by MRI and cognitive testing on day 3. Participants will then undergo a 25-day 
washout of study medication and will then, again, receive hydrocortisone or placebo for 3 days, followed by MRI and cognitive 
testing. The order in which participants will receive hydrocortisone vs. placebo will be randomized by a study statistician. 
 
 
 
4.  Research Plan / Description of the Research Methods:   
4.a.  Provide a comprehensive narrative describing the research methods.   
     1) Provide the order in which tests/procedures will be performed,  
     2) Provide the setting for these events and a description of the methods used to protect privacy during the study.   
     3) Provide the plan for data analysis (include as applicable the sample size calculation) 
 
Please respond to all components of this item, or clearly indicate which components are not applicable. 
 
 
Informed consent and all study procedures, other than neuroimaging, will be conducted at BL8.224 or remotely through secure 
video conferencing software (e.g. Zoom, Teams). Neuroimaging will be done at the AIRC. When informed consent is conducted 
remotely, DocuSign will be used to obtain signatures. Please see the next page for the assessment schedule. 
 
Methods used to protect privacy: Deidentified data will be stored in REDCap – a self-managed, secure, web-based solution 
that is designed to support data collection strategies for research studies. Only researchers associated with the study will have 
access to any protected health information (PHI). This information will not be stored on REDCap. Identifying information will be 
kept in a separate password-protected file only accessible to the PI and the research team on a need-to-know basis. Data will be 
analyzed by group, and subjects will be identified only by a subject ID number to protect their confidentiality. Researchers will 
destroy the personal identifiers upon completion of data collection for the study. 
 
Data analysis plan: 
Aim 1: Determine the effect of cortisol on task-driven hippocampal activation using, for the first time, high-resolution 
(1.5 mm isotropic) fMRI of hippocampal subfields (i.e., DG/CA3, CA1, subiculum). The design is a two-period crossover with 
randomized order of treatment conditions, and the primary interest is in the treatment effect on hippocampal subfield activation, 
estimated as the within-subjects difference in hippocampal subfield activation between the hydrocortisone and placebo treatment 
conditions. The index of hippocampal subfield activation is a beta-weight of the contrast of the task-active condition vs. the 
control condition (e.g. novel vs. familiar in the Novelty Detection task and lure correct rejections vs. false alarms in the Mnemonic 
Discrimination task). We will use linear mixed effects regression to estimate the following model of DG/CA3 activation,
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Aim 2: Determine the effect of cortisol on hippocampal subfield volume using high-resolution structural MRI. Using the 
same randomized regression approach described above we will assess mechanistic aim 2.  
Aim 3: Assess changes in hippocampal NAA, Glu, Cho and mI with cortisol using 1HMRS. Similarly, changes in 
spectroscopy will be assessed using the randomized regression utilized in the previous aims. 
Aim 4: Determine the effect of cortisol on declarative and visuospatial memory. We will estimate the treatment effects on 
declarative memory using the same linear mixed model setup as the primary aim.   
Aim 5: Examine whether sex, stress, early life adversity, age, physical activity, GCR number or sensitivity, or changes in 
sleep during cortisol administration, predict hippocampal CS response, as assessed by memory testing and 
neuroimaging. We will assess treatment moderation by sex, stress, early life adversity, age, physical activity, and changes in 
sleep using the modeling setup described in the primary aim with additional terms added to the model. To assess the moderation 
of a dichotomous variable (i.e., sex), a group indicator (male vs. female) will be added to the regression model (

Form A 
IRB # 
STU  2018-0360 
 
STU2018-0360, Brown, FormA-Protocol, Mod_21, 06-14-23 
 
3 
vMar2018 
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Aim 6: Explore the effects of cortisol on resting state regional functional connectivity, and whole brain connectomics. 
As discussed in the primary aim, the treatment effects on resting state functional connectivity will be assessed using a 
randomized regression in a traditional longitudinal cast. The key indices of interest will be overall measures of network integrity 
(e.g., degree, centrality, rich club architecture, etc.).  
Aim 7: Explore the impact of depressive symptoms on memory and hippocampal structure, activation, connectivity and 
1HMRS outcomes in response to hydrocortisone administration. Depression as a moderator will be assessed similarly to the 
moderators proposed in aim 5. However, a dichotomous indicator variable representing baseline group assignment (depressed 
vs. healthy control) will also be included in the model. 
 
Sample size determination: 
Aims 1, 2, 3, 4 and 6: Complete data from 168 (84 subjects per group) will provide 90% power to detect a treatment effect on 
hippocampal activation of magnitude 0.08 or greater (correspondingly, d ≥ 0.34), based on the findings of Brown et al. (2013).34 
The magnitude of the treatment effect observed by Brown et al. (2013)34 was 0.16. This is a very conservative estimate because 
we anticipate enrolling 188 (94 per group) expecting no more than 10% attrition. If attrition rates are abnormally high, at 
approximately 20%, the completer sample of 150 (75 per group) would provide 80% power and provide sufficient power to detect 
a statistical difference with an effect size of d = 0.34. Complete data from 168 (84 per group) subjects will provide 90% power to 
detect a treatment effect on hippocampal volume of magnitude 0.06 mm3 or greater, based on the findings of Brown et al. 
(2015)43 and to detect a treatment effect on declarative memory of magnitude 3.31 or greater, based on the findings of Brown et 
al. (2013).34  The magnitude of the treatment effect on hippocampal volume observed by Brown et al. (2015)43 was 0.12 mm3, 
and the magnitude of the treatment effect on declarative memory observed by Brown et al. (2013)34 was 4.25. To power the 
study for the spectroscopy aims, we used data from a study of patients receiving prednisone for medical illnesses vs. disease 
matched controls.30 The participants were receiving corticosteroids for a longer duration than in the proposed study, but no 
studies examining more acute exposure were available. Based on the NAA/Cr values reported we expect a medium effect size 
(~d = 0.54). Assuming we have complete data on more than 68 (34 per group) participants we will have approximately 90% 
power to detect a significant difference in spectroscopy data. This is a conservative estimate given other effect sizes observed in 
similar work were much larger (d = 0.84) which would only need complete data from 40 subjects (20 per group) to observe 96% 
power. For clinical aim 4, complete data from 136 (68 per group) subjects will provide 90% power to detect a treatment effect on 
declarative memory of an effect size of d = 0.38 or greater, based on the findings of Brown et al. (2013).34 In the case of high 
attrition rates (> 28%) we would still have over 90% power to observe a significant effect on memory changes.  Although data are 
not available for a sample size estimate for the exploratory aim of rsFC, a sample size of 168 (84 per group) will provide 80% 
power for an effect size of d = 0.30 which is smaller than effect sizes observed in previous work referenced above.  
 
Aims 5 and 7: Complete data from 48 participants (50% women) will provide 90% power to detect treatment moderation by sex 
of magnitude 0.16 for hippocampal activation, 0.12 mm3 for hippocampal volume, and 6.63 for declarative memory (all 
corresponding to a medium effect size of d = 0.68).43 We will assess treatment moderation in the same way but replacing the 
indicator of female sex with depressed status. Based on previous studies, a difference in declarative memory performance 
following CS administration between depressed people and controls has a large effect size (d = 1.1).54 Using the conservative 
approach of powering the study for the lowest observed magnitude of d = 0.34 allows adequate power (≥ 90%) when assessing 
effects with higher magnitudes.  
 
References for sample size calculations: 
Brown ES, Lu H, Denniston D, et al. A randomized, placebo-controlled proof-of-concept, crossover trial of phenytoin for 
hydrocortisone-induced declarative memory changes. J Affect Disord. 2013;150(2):551-558. 
Brown ES, Jeon-Slaughter H, Lu H, et al. Hippocampal volume in healthy controls given 3-day stress doses of hydrocortisone. 
Neuropsychopharmacology. 2015;40:1216-1221. 
 

Form A 
IRB # 
STU  2018-0360 
 
STU2018-0360, Brown, FormA-Protocol, Mod_21, 06-14-23 
 
4 
vMar2018 
 
 

Form A 
IRB # 
STU  2018-0360 
 
STU2018-0360, Brown, FormA-Protocol, Mod_21, 06-14-23 
 
5 
vMar2018 
 
Assessment Schedule 
Instrument 
Baseline (Visit 
1) 
Visit 
2 
2 days (Visit 3 occurs on Day 3)  
Visit 
3 
Washout (25 days)  
Visit 
4 
2 days (Visit 5 occurs on Day 3)  
Visit 
5 
Informed consent 
X 
 
 
 
 
Medical and psychiatric history 
X 
 
 
 
 
Concomitant medication review 
X 
X 
X 
X 
X 
Physical exam 
X 
 
 
 
 
SCID-CV for DSM 5 
X 
 
 
 
 
Quick Inventory of Depressive Symptomatology (QIDS-
C) 
 
X 
X 
X 
X 
X 
Young Mania Rating Scale (YMRS) 
X 
X 
X 
X 
X 
Columbia Suicide Severity Rating Scale (C-SSRS) 
 
X 
 
X 
 
X 
Systematic Assessment for Treatment Emergent Event 
(SAFTEE) 
X 
 
X 
 
X 
Rey Auditory Verbal Learning Test (RAVLT) 
 
X 
 
X 
 
X 
Ruff Light Trail Learning (RULIT) 
X 
 
X 
 
X 
Volunteer Health Questionnaire 
X 
 
 
 
 
Weekly Questionnaire 
 
X 
X 
X 
X 
Prodromal Questionnaire – Brief Version (PQ-B) 
X 
 
X 
 
X 
Perceived Stress Scale (PSS-10) 
Childhood Trauma Questionnaire (CTQ) 
International Physical Activity Questionnaire (IPAQ) 
Treatment Impressions Inventory (TII) 
X 
X 
X 
X 
 
 
 
 
Internal Status Scale (ISS) 
 
 
X 
 
X 
Blood work (CBC, CMP, morning cortisol) 
CMP – 8.5 mL; CBC – 4 mL; Cortisol – 10 mL 
X 
 
X 
 
X 
Blood work (GCR analysis and epigenetics, 2 x 8.5 mL) 
X 
 
 
 
 
Blood work (progesterone in naturally cycling women) 
Progesterone – 10 mL 
 
 
X 
 
X 
Blood work (Glucocorticoid) 
X 
 
X 
 
X 
Vitals 
X 
 
 
 
 
Electrocardiogram (ECG) 
X 
 
X 
 
X 
Urine pregnancy test (UPT) 
X 
 
X 
 
X 
Randomization 
 
X 
 
 
 
Begin 3-day course of hydrocortisone or placebo 
 
X 
 
X 
 
Begin 3-day actigraphy monitoring 
 
X 
 
X 
 
Structural and functional MRI, spectroscopy 
 
 
X 
 
X 
Follow-up with a clinician 
 
X 
X 
X 
X 
Adverse events review 
 
X 
X 
X 
X 
Exit survey 
 
 
 
 
X 
Approximate time/visit 
3 hr 
45 m 
3.5 hr 
45 m 
3.5 hr 

Form A 
IRB # 
STU  2018-0360 
 
STU2018-0360, Brown, FormA-Protocol, Mod_21, 06-14-23 
 
6 
vMar2018 
 
4.b.  List of the study intervention(s) being tested or evaluated under this protocol 
 
N/A -  this study does not test or evaluate an intervention.    Skip to item 4.d. 
# 
Study intervention(s) being tested or evaluated under the protocol 
 
 
 
Add or delete rows as needed 
 
Affiliate 
 
Place a check next to 
institution(s) where the  
intervention will be 
performed 
Local Standard 
Practice?  
Indicate whether the 
intervention is 
considered 
acceptable practice 
locally for applicable 
institutions 
1 
Hydrocortisone 
☒ UTSW 
☐ Yes 
☐ PHHS 
☐ Yes 
☐CMC 
☐ Yes 
☐THR 
☐ Yes 
☐TSRH 
☐ Yes 
☐ Other: _____ 
☐ Yes 
 
 
4.c.  Risk:Benefit Analysis of study interventions being tested or evaluated under this protocol 
For each study intervention identified in section 6b above, complete a risk:benefit analysis table. 
 
(Two tables are provided, copy & paste additional tables as needed or delete both tables if this study does not test an 
intervention) 
 
 

Form A 
IRB # 
STU  2018-0360 
 
STU2018-0360, Brown, FormA-Protocol, Mod_21, 06-14-23 
 
7 
vMar2018 
4.c. 
Study Intervention #1 
Hydrocortisone 
List each group exposed to this 
intervention on a separate line. 
(e.g., experimental, control, Arm A, Arm B, 
etc) 
Or state All Groups/Subjects 
For each group, list the benefits of this intervention.  (Benefits can be directly from 
the intervention or from a monitoring procedure likely to contribute to the subject’s 
well being).  If there are no benefits, state “none”. 
All subjects 
All subjects will receive ongoing monitoring for their depressive symptoms. 
However, this is not a treatment study and the researchers are not evaluating the 
effectiveness of hydrocortisone in treating depression. The researchers are 
interested in whether a short 3-day dose of hydrocortisone has different effect on 
the brain and cognition in depressed vs. non-depressed individuals. Participants 
will also receive blood work, ECG, progesterone level testing, diagnostic interviews, 
psychiatric symptom assessment, cognitive assessments, and psychiatric care. 
Thus, we feel that the risks, although clearly present, are greatly outweighed by the 
benefits of this study. 
 
 
If you are requesting a Waiver of Informed Consent, complete the table below. 
 
If you have a consent form, list the reasonably foreseeable risks in the consent form (and do not complete this section).   
 
List the risks according to the probability (likely, less likely or rare) and magnitude (serious or not serious). 
(include: 1) expected adverse events; 2) rare and serious adverse events; 3) all other psychological, social, legal harms) 
Do not delete frequency.  Frequency must be estimated because it will assist you with determining which adverse events will require 
prompt reporting.   
 
Not serious 
Serious  
Likely 
These risks are expected to occur in 
more than 20 out of 100 subjects. 
• 
N/A (listed in consent) 
• 
N/A (listed in consent) 
 
Not serious 
Serious 
Less likely  
These risks are expected to occur in 5-
20 subjects or less out of 100 subjects. 
• 
N/A (listed in consent) 
• 
N/A (listed in consent) 
 
 
Serious 
Rare  
These risks are expected to occur in 
less than 5 subjects out of 100  
 
• 
N/A (listed in consent) 
 
 
 
 

Form A 
IRB # 
STU  2018-0360 
 
STU2018-0360, Brown, FormA-Protocol, Mod_21, 06-14-23 
 
8 
vMar2018 
 
4.d. List ALL other research procedures or components not listed in table 4.b. 
        The combination of Tables 4b and 4d should account for all of the research 
procedures that will take place during this study. 
 
Consider grouping similar procedures under a single component (e.g., blood work, CT = safety 
assessments) 
 
 
 
# 
Research component 
• 
individual 
procedures 
 
example: 
Eligibility Assessments 
• 
History and 
physical 
• 
Questionnaire 
• 
Laboratory tests 
Add or delete rows as needed 
Column A 
Local Standard 
Practice Indicate the 
number of times each 
procedure will be 
performed as stipulated 
in the research plan that 
would be performed if 
the participant were not 
participating in the 
study. 
Column B 
Research Only  
Indicate the number of times 
each procedure will be 
performed solely for research 
purposes (meaning that the 
participant would not undergo 
the same number of 
procedures or would not 
undergo the procedure(s) at 
the same frequency if they 
were not participating in the 
study) 
Column D 
Risks 
If you are requesting a Waiver of Informed 
Consent, complete the table below. 
 
List the reasonably expected risks for each procedure 
or group of procedures under the following categories 
as appropriate: 
• Serious and likely; 
• Serious and less likely; 
• Serious and rare; 
• Not serious and likely; 
• Not serious and less likely 
1 
Baseline (Visit 1) 
 
 
N/A – not requesting a waiver of consent 
 
Informed consent 
0 
1 
 
 
Psychiatric/medical history 
0 
1 
 
 
Physical exam 
0 
1 
 
 
Concomitant medication 
review 
0 
1 
 
 
SCID-CV for DSM 5 
0 
1 
 
 
RAVLT 
0 
1 
 
 
RULIT 
0 
1 
 
 
QIDS-C 
0 
1 
 
 
YMRS 
0 
1 
 
 
PSS-10 
0 
1 
 
 
CTQ 
0 
1 
 
 
C-SSRS 
0 
1 
 
 
SAFTEE 
0 
1 
 
 
IPAQ 
0 
1 
 
 
Blood draw 
0 
1 
 
 
ECG 
0 
1 
 
 
Urine pregnancy test 
0 
1 
 
 
PQ-B 
0 
1 
 
 
TII 
0 
1 
 
2 
Visits 2 and 4 
 
 
 
 
QIDS-C 
0 
1 
 
 
YMRS 
0 
1 
 
 
 
 
 
 
 
Clinician follow-up 
0 
1 
 
 
3-day actigraphy 
0 
1 
 
 
3-day hydrocortisone vs. 
placebo 
0 
1 
 
3 
Visits 3 and 5 
 
 
 
 
RAVLT 
0 
1 
 
 
RULIT 
0 
1 
 
 
PQ-B 
0 
1 
 
 
QIDS-C 
0 
1 
 
 
YMRS 
0 
1 
 
 
C-SSRS 
0 
1 
 
 
SAFTEE 
0 
1 
 

Form A 
IRB # 
STU  2018-0360 
 
STU2018-0360, Brown, FormA-Protocol, Mod_21, 06-14-23 
 
9 
vMar2018 
 
Internal Status Scale 
0 
1 
 
 
Blood draw 
0 
1 
 
 
ECG 
0 
1 
 
 
Clinician follow-up 
0 
1 
 
 
MRI (structural and functional) 
0 
1 
 
 
1HMRS (spectroscopy) 
0 
1 
 
 
Urine pregnancy test 
0 
1 
 
4 
Visit 5 
 
 
 
 
Exit survey 
0 
1 
 
 

Form A 
IRB # 
STU  2018-0360 
 
STU2018-0360, Brown, FormA-Protocol, Mod_21, 06-14-23 
 
10 
vMar2018 
 
5.  Safety Precautions.  (Describe safeguards to address the serious risks listed above.) 
a.  Describe the procedures for protecting against or minimizing any potential risks for each of the more than minimal risk 
research procedures listed above. 
The primary risks of this study are potential medication side effects to a brief 3 day exposure to the study medication and a 
possible delay in treating depression. PI Brown has extensive clinical and research experience with depressed patients, 
including the studies involving the use of hydrocortisone and neuroimaging. At all visits, the participants will also be assessed 
by a licensed clinical provider and monitored for side effects, worsening of mood symptoms, and suicidality. 
 
Brief hydrocortisone administration appears to be safe and well tolerated. However, participants will be informed of all 
potential risks of brief corticosteroid exposure. The participants may experience a brief and reversible change in declarative 
memory while receiving hydrocortisone. 
 
At the MRI scanner, participants will fill out an MRI screening form and will also be screened by the MRI technologist to 
ensure it is safe for the participant to undergo the scan. Participants will also be informed that they may stop the imaging 
session at any time, and participants with claustrophobia will be excluded during the pre-screen. The mock scanner will be 
available if needed to ensure participants feel comfortable in an enclosed space. Participants will be asked to press the call 
button in the scanner if they experience any discomfort, and will be immediately removed from the scanner. Both the MRI 
technologist and the research assistant will be present during the entire MRI session to monitor patient safety. A Rapid 
Response Team will be called should the patient experience a medical emergency. 
 
All assessments will be performed by trained research personnel experienced in working with the research population 
involved in the study. Breaks will be utilized as needed to reduce participation burden and psychological stress. Blood will be 
drawn by a certified phlebotomist. A urine pregnancy test will be administered to all participants of childbearing potential, and 
pregnant or breastfeeding women will be excluded from the study. 
 
Another risk will include premenopausal women. Participants will be asked to use an acceptable and effective form of birth 
control during the study. A hysterectomy or bilateral tubal ligation is acceptable because these women continue to have 
menstrual cycles. Women with an ovariectomy (“surgical menopause”) will be excluded. Women currently taking estrogen 
containing oral contraceptives will be excluded due to the possible effects of these medications on cortisol levels and the 
brain’s response to cortisol. Non-estrogen containing contraceptives including progestin-only pills (e.g. Micronor, Nor-QD, or 
Camilla), implants such as Nexplanon or Implanon that contain the progestin etonogestrel, ParaGard IUD (a copper-T device 
that contains no hormone), as well as barrier methods are acceptable. 
 
The PI on the study is a board-certified psychiatrist and the study clinician team includes two psychiatrists, a psychiatric nurse 
practitioner and a psychiatric physician assistant, all with extensive experience managing clinical trial patients with mood 
disorders. Should a psychiatric emergency (e.g., active suicidal ideations with plan and intent) arise during the screening visit 
(or any other study visit), the subject will be assessed by a clinician, 911 will be called, and the subject will be escorted to the 
Clements Emergency Room or Parkland Psychiatric Emergency Room. 
 
b.  Where appropriate, discuss provisions for ensuring necessary medical or professional intervention in the event of adverse 
events, or unanticipated problems involving subjects. 
Should a medical emergency arise during the study participation, 911 will be called and a participant will be escorted to 
Clements or Parkland Emergency Room. All investigators and clinicians on the study are experienced psychiatric care 
providers. Should a psychiatric emergency arise that require inpatient monitoring, 911 will be called and a participant will be 
escorted to the Clements Emergency Room or Parkland Psychiatric Emergency Room. In the event of an adverse event or an 
unanticipated problem that does not require emergency hospitalization, a participant will be carefully monitored by the PI and 
the PI’s team and the appropriate referrals will be arranged as needed for the participant. All UPIRSOs will be reported to the 
IRB board according to the specified guidelines. 
c.  Will the safeguards be different between/among groups?   
Yes 
 
No 
N/A