Clinical trial NCT02826577
Conditions: Perceived Social Isolation
Sponsor: University of Chicago
Start date: 2017-05-01; Completion date: 2022-12-21
Enrollment: 34 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
No studies to date have examined the effects of pregnenolone on hypervigilance for social threat in individuals with perceived social isolation (PSI). We therefore are conducting a double-blind randomized research study combining three validated behavioral paradigms on social threat attention, perception of others, and emotion regulation with high-density electrical neuroimaging to probe the neuro-circuitry of social threat processing in young adults high in perceived social isolation two hours after the oral administration of 175mg pregnenolone (N = 24), 400mg of pregnenolone (N = 24), or placebo (N = 24). Such research has the potential to yield important insights into the neurobehavioral mechanisms of pregnenolone on hypervigilance for social threat and perception of others--- a first key step toward the development of adjunctive pregnenolone therapy in individuals with PSI.

Detailed description:

Arms: arm 1: \- Single dose of 175mg arm 2: \- Single dose of 400mg arm 3: \- Single dose of placebo arm 4: \- No intervention
Interventions: intervention 1: Pregnenolone 175mg intervention 2: Pregnenolone 400mg intervention 3: Placebo
Intervention descriptions: intervention 1: Single Dose 175mg intervention 2: Single Dose 400mg intervention 3: Single Dose

Protocol documents:
Prot_SAP_003.pdf: 
1 
 
Effects of Pregnenolone on Perceived Social Isolation 
 
IRB16-0834 
Protocol Version July 26, 2019 
NCT02826577 
 
 


EEG and Pregnenolone Project 
 
Protocol Narrative 
2 
Effects of Pregnenolone on Perceived Social Isolation 
 
 
PROJECT ABSTRACT 
Perceived social isolation (PSI), also known as loneliness, has been shown to increase depression 
in humans and animal models and to increase the risk of early mortality by 26%. Despite the 
well-known effects of pregnenolone (PREG) in alleviating depressive behavioral effects of social 
isolation in mice and post-traumatic disorders and depressive symptomatology in humans, no 
studies to date have examined the effects of PREG on humans with PSI as well on a specific 
mechanism of action underlying PSI, such as increased hypervigilance to social threat- a vital 
first step in the novel use of PREG as an adjunctive therapy for attentional bias to social threats 
in individuals with PSI. We therefore propose a randomized, double-blind, between-subjects 
design, where three validated behavioral paradigms on social threats will be combined with high-
density electrical neuroimaging to probe the neuro-circuitry of social threat processing in male 
adults (aged 21-80) high in PSI.  
 
 
 


EEG and Pregnenolone Project 
 
Protocol Narrative 
3 
1. BACKGROUND AND SIGNIFICANCE 
A growing body of research suggests that the perception of social isolation (PSI, or what 
has been termed loneliness; Cacioppo and Patrick, 2008) has detectable effects on attention, 
including increased vigilance for negative social stimuli, such as social threats (Cacioppo & 
Hawkley, 2009; Cacioppo, Balogh, Cacioppo, 2015, Cacioppo, Bangee, et al., 2015). This focus 
on self-preservation may promote short-term survival but has been shown to have long-term costs 
for health and well-being (Cacioppo & Hawkley, 2009). For instance, using a modified emotional 
Stroop task, we found that lonely subjects, relative to nonlonely subjects, show greater Stroop 
interference specifically for negative social relative to negative non-social words (Egidi, Shintel, 
Nusbaum, & Cacioppo, 2008). Stroop interference has been used to gauge the implicit processing 
of stimuli, so these results suggest that PSI is associated with a heightened accessibility of negative 
social information. Similarly, in an investigation of the effects of subliminal priming on the 
detection of painful facial expressions, Yamada and Decety (2009) found that PSI is associated 
with greater sensitivity to the presence of pain in dislikable faces, as gauged by the sensitivity 
index, d’, from signal detection theory. In an eye tracking study, lonely and nonlonely young adults 
viewed various positive and negative social scenes and exhibited different fixation patterns. 
Individuals high in PSI (or loneliness) are more likely to first fixate on and to spend a greater 
proportion of their initial viewing time looking at socially threatening stimuli in a social scene, 
whereas individuals low in PSI are more likely to first fixate on and spend a greater proportion of 
their initial view time looking at positive stimuli in a social scene (Bangee, Harris, Bridges, 
Rotenberg, & Qualter, 2014). Combining high-density electrical neuroimaging with a behavioral 
task including social and non-social threat (and neutral) IAPS pictures known to probe pre-
attentional mechanism for social threats (the pre-attentional social threat task, PAST, Cacioppo, 
Bangee, et al., 2015), we showed that individuals high in PSI (N = 10) differentiate social threat 
images from non-social threat stimuli more quickly (~116 ms after stimulus onset) than individuals 
low in PSI (N = 9; ~252 ms after stimulus onset) brains. That speed of threat processing in lonely 
individuals is in accord with the evolutionary model of loneliness that indicates feeling socially 
isolated (or on the social perimeter) leads to increased attention and surveillance of the social world 
and an unwitting focus on self-preservation. Brain source estimates expanded these results by 
suggesting that lonely (but not nonlonely) individuals showed early recruitment of brain areas 
involved in visual attention and self-representation (Cacioppo, Bangee et al., 2015). The next step 
is to investigate how and when this early hyper-attention for social threats in individuals high in 
PSI may be reduced.  
For the past decade, preclinical and clinical data suggest that pregnenolone may be a 
promising therapeutic in reducing a wide range of emotional responses from anxiety- and 
depressive-like behaviors. Pregnenolone is neuroprotective, reduces anxiety, and enhances 
learning, memory, and myelination. Treatment with pregnenolone elevates allopregnanolone 
(ALLO, a neurosteroid that enhances GABAA receptor responses) and pregnenolone sulfate (a 
positive NMDA receptor modulator). In turn, exogenous administration of the neurosteroid 
allopregnanolone (ALLO) has also been shown to hold significant promises for reducing a wide 
range of emotional responses in humans with anxiety, depressive-like, and aggressive behaviors 
and inducing changes in responses to contextual fear conditioning in rodent models of emotional 
dysfunction in social isolation, and ALLO blockade impairs social and affective functioning. 
Although studies in humans are less abundant, they are broadly consistent with animal findings. 
For instance, cerebrospinal fluid levels of ALLO are reduced in women with major depressive 
disorder (MDD) and post-traumatic stress disorders (PTSD), and increase with successful 


EEG and Pregnenolone Project 
 
Protocol Narrative 
4 
pharmacological treatment (Amin et al., 2006; van Broekhoven et al., 2003; Uzunova et al., 
1998; Rasmusson et al., 2006; Strohle et al., 1999). Interestingly, various antidepressant agents 
(including fluoxetine, norfluoxetine, fluvoxamine and paroxetine) elevate ALLO brain levels 
(e.g., Uzunova et al., 1998; Romeo et al., 1998; Marx et al., 2006), leading to the suggestion that 
ALLO induction might be an important mechanism for the antidepressant effects of SSRIs (e.g., 
Pinna et al., 2006, 2009). Based on these observations, it has been suggested that ALLO 
dysregulation may contribute to the development of neuropsychiatric disorders, and that 
restoration of ALLO regulation may be a potential pathway for symptomatic improvement 
(Pinna & Rasmusson, 2011). Because a reduction in the synthesis of ALLO has been observed 
during social threat processing, potentially by reducing brain-derived neurotrophic factor 
(BDNF) regulation and increasing hypothalamic–pituitary–adrenal (HPA) activity through the 
hippocampus, amygdala, and bed nucleus of the stria terminalis (BNST (Cacioppo et al., 2015, 
Cacioppo & Cacioppo, 2015), we hypothesize that exogenous administration of ALLO 
precursor, pregnenolone, may help reduce hyperattention to social threats in PSI. Little is known, 
however, on the effects of oral administration of pregnenolone on hyperattention to social threat.  
Historically, treatment with PREG has been found to alleviate the depressive behavioral effects 
of social isolation in mice and depressive symptomatology in humans by elevating ALLO. 
Therefore, PREG directed at up-regulating ALLO (neurosteroid deficit target) in individuals high 
in PSI could reduce PSI and improve its behavioral effects. The doses we propose in the current 
project have been shown to up-regulate ALLO: A single oral dose of 175 mg PREG approximately 
doubles ALLO serum levels over the course of 4–8 h, while a single oral dose of 400mg of PREG 
triples ALLO serum levels over the course of two hours in healthy non-psychiatric subjects with 
normal neuro-active steroid levels at baseline. One potential mechanism for PREG’s ability to 
directly impact emotion neuro-circuitry is the up-regulation of ALLO in the central nervous 
system. Sripada and colleagues (2013), for instance, demonstrated that a single oral administration 
of PREG (400mg) reduces activation of brain areas involved in negative emotions, increases 
activity in the dorsal medial prefrontal cortex (dMPFC), and enhances connectivity between the 
amygdala and dMPFC, an effect that was associated with reduced self-reported anxiety. However, 
the effect of PREG on other negative emotional mechanisms, such as attentional bias to social 
threats and depressive symptomatology remains unknown. Our proposed novel use of the currently 
available dietary supplement, PREG, on PSI is based on formative animal work on social isolation 
by our colleague, Dr. Pinna. In a rodent model, Dr. Pinna demonstrated that: i) the exaggerated 
contextual fear responses expressed by socially-isolated mice can be normalized by increasing 
ALLO levels; ii) HPA dysfunction and impairment of hippocampal neurogenesis respectively can 
be normalized or prevented with the administration of exogenous ALLO either during or following 
a period of chronic stress (and iii) the establishment of depressive/anxiety-like behaviors in rodents 
can be precluded also with administration of exogenous ALLO-targeted treatment. 
2. Purpose 
The goal of the proposed research, which is based on prior human and animal work, is to test a proof-of-
concept that acute oral administration of PREG reduces PSI in male adults (aged 21-80) high in PSI. 
Validated self-report measures (e.g., depression, anxiety, objective social isolation, life 
satisfaction) will also be used to examine changes in symptom severity and subjective feelings. The 
long-term objective of this project is to advance the use of PREG at remediating the protracted 
reduction in the neurosteroid, ALLO in individuals high in PSI and thereby reduce PSI and 
improve social withdrawal. The proposed project will employ a randomized between-subjects 


EEG and Pregnenolone Project 
 
Protocol Narrative 
5 
design, where a validated behavioral paradigm on social threat attention , intention understanding, 
and perception of others will be combined with validated measures of depressive symptomatology 
in male adults (aged 21-80) high in PSI. 
Reducing PSI, attentional biases, and depressive symptomatology through the use of a 
pharmacological treatment may, therefore, have potential benefits for health and well-being. 
Until now, a main challenge for physicians and mental health clinicians has been to become 
sufficiently informed about the scientific definition of PSI (or loneliness) so that other mental 
disorders were not mistakenly diagnosed and treated when PSI was either the primary presenting 
problem or the cause of the depression for which treatment was sought44. For decades, many 
clinicians believed that PSI was simply an aspect of depression with no conceptual distinctions 
worthy of study1. There is now considerable evidence showing that PSI and depression (as well as 
other factors such as introversion, neuroticism, objective social isolation, & social support) are 
separable and that PSI increases the risk for (or leads to) depression. For instance, even after 
controlling for objective social isolation and other potential confounding factors, PSI contributes 
to a constellation of physical and psychiatric dysfunctions44-48. PSI is also a risk factor for 
alcoholism, suicidal thoughts, aggressive behaviors, social anxiety, and impulsivity. In addition, 
PSI is a risk factor for cognitive decline and the progression of Alzheimer’s Disease, recurrent 
stroke, obesity, increased vascular resistance and elevated blood pressure, increased hypothalamic 
pituitary adrenocortical (HPA) activity, diminished immunity, an under-expression of genes 
bearing anti-inflammatory glucocorticoid response elements and an upregulation of pro-
inflammatory gene transcripts, and premature mortality. Moreover, meta-analyses indicate that 
cognitive/behavioral interventions have proven to be largely ineffective. Thus, a pharmacological 
treatment for PSI is timely needed. Despite its public health importance, there is no 
pharmacological treatment for PSI. In addition, a key neurobehavioral characteristic of individuals 
high in PSI is an increased implicit attentional bias for social threats, which has been linked to an 
early evoked neurophysiological response and underlie unsuccessful social connections and social 
withdrawal. This focus on self-preservation reinforces Cacioppo and colleagues’ seminal 
evolutionary model of PSI8 that emphasizes the role of hyper-vigilance to social threats as a 
mechanism promoting short-term survival but also as having long-term costs for health and well-
being.  
 
3. Innovation 
In the present project, 224 PSI subjects will be randomized to a single oral dose of PREG 400mg 
(n=112), or placebo (PBO, n=112), while behavioral responses and neuro-active steroid levels will 
be measured before and after study drug/placebo administration. This project is innovative is 
several ways. First, it is the first study of its kind to test the effect of PREG in individuals high in PSI. 
Second, 
it 
strategically 
combines 
multiple 
lines 
of 
investigation 
– 
behavioral, 
psychopharmacology, neuroimaging, and advanced statistical techniques (e.g. brain microstate 
identification via root mean square error modeling; bootstrapping) --- often carried out separately. 
More precisely, the proposed study aims to test a proof-of-concept that acute oral administration of 
PREG reduces PSI and its depressive symptomatology and improves attentional bias for social 
threats in a double-blind randomized research study combining a validated behavioral paradigm 
on social threat attention, intention understanding, and perception of others in male adults (aged 
21-80) high in PSI. Validated self-report measures (e.g., depression, anxiety, objective social 


EEG and Pregnenolone Project 
 
Protocol Narrative 
6 
isolation, life satisfaction) will also be used to examine change in symptom severity and subjective 
feelings. Third, it tests multiple layers of ‘target engagement’ including ALLO levels (determined 
by the state-of-the-art gas chromatography-mass spectrometry (GC-MS) quantification 
technology) in serum and saliva, and behaviors, and proximal and distal clinical outcomes. 
Importantly, the proposed study is the first to use PREG to engage the target ALLO to improve 
PSI. Such research has the potential to yield important insights into the neurobehavioral 
mechanisms of PREG on PSI and its underlying behavioral effects--- a first key step toward the 
development of adjunctive PREG therapy in individuals with PSI. Moreover, the proposed project 
is novel as it will attempt to establish PREG, a dietary supplement, as an agent intended to 
remediate the protracted reduction in the neurosteroid, ALLO, as a treatment for PSI in humans. 
The overarching objective is to use an acute, daily oral dose of PREG as an “ALLO normalizer” 
for six weeks to increase the likelihood patients with PSI will benefit from PREG. If successful, 
the novel use of PREG has the potential to reduce PSI and provide PSI patients with relief from 
PSI-related symptoms and disorders.  
4. Rationale for using pregnenolone (PREG), as opposed to ALLO: The rationale for a 
PREG approach is that PREG is an ALLO precursor that is lipophilic and readily crosses the 
blood brain barrier—a characteristic that makes it the first line of pharmacological treatment for 
PSI. PREG deficiency leads to depression and even suicide and there are also studies showing 
impairment of cognition and memory and replacement therapy reverses these effects. PREG is 
the precursor of neurosteroids and also TSPO agonists that increase levels of PREG and 
downstream steroids, including ALLO have been suggested for anxiety/depression treatment and 
tested in clinical trials and these molecules show advantages for the treatment of several 
neuropathologies63,64. It is important to emphasize that in this study the dose-response design 
followed by determining the levels of neurosteroids (e.g., ALLO) aims at a normalization of the 
PSI-induced downregulation of the serum neuro-active steroid levels rather than increasing them 
to supraphysiologic levels. Therefore, measuring neuro-active steroids immediately after 
completion of treatment will guide eventual adjustment of doses and therefore a better utilization 
of resources during the Present project. The novel application of PREG in the present study is 
also reinforced by the compelling findings by Sripada and colleagues, who showed an acute, oral 
dose (400mg) of PREG up-regulate ALLO in young adults (age between 18-32) and reduce 
activation of brain areas underlying negative emotions processing. An alternative means of 
increasing ALLO would be to administer it directly. However, such approach would increase the 
risk of undesirable side effects (e.g., sedation) as it would globally impact ALLO levels even in 
brain regions where levels are physiologically low. Also, while synthetic neurosteroids (e.g., 
Ganaxolone) offer another potential approach, they are currently under development or require 
further testing for potential medical use in humans. Because SSRI, such as fluoxetine (FLX), are 
also known to elevate ALLO levels, a FLX approach could have been also considered. However, 
FLX has a low response rate, which varies from 30-50%, and a constellation of undesirable side 
effects. Thus, pre-clinical work signifying PREG, a generally well-tolerated dietary supplement, 
up-regulates ALLO suggests it is a viable approach to engage ALLO in humans. Clinical trials 
that have used a PREG approach on negative emotion processing, schizophrenia, or on 
inflammatory diseases, consistently show that PREG 25–500 mg/day has minimal side effects, 
and does not affect weight, heart rate, blood pressure (even in patients with hypertension), 
menstrual cycle, or glucose levels (either in diabetics or non-diabetics. 


EEG and Pregnenolone Project 
 
Protocol Narrative 
7 
 Rationale for selected dose range in the present project: Here, 224 subjects high in PSI will 
be randomized to a single oral dose of PREG 400mg (n=112), or placebo (PBO, n=112) to 
ascertain dose of administration. The rationale for the selected dose range is the following: First, 
clinical trials showed that PREG 25–500 mg/day is safe and well tolerated in humans. Second, 
Sripada and colleagues made the compelling basic science discovery that a single dose (400mg) 
of PREG up-regulates ALLO in young adults (See Fig. 1) and reduces activation of brain areas 
underlying negative emotions processing. 
Fig. 1. Steroid and metabolite levels in 
Sripada et al.’s 2013. *T-tests were 
conducted on change scores (steroid levels 
at endpoint minus steroid levels at 
baseline). Pregnenolone group received an 
acute, oral dose of PREG 400mg.  
 
Based on pharmacokinetic data in humans, we expect the peak serum concentration of ALLO to 
occur approximately 2 hours after acute, oral administration of PREG 400mg. Saliva levels will 
be measured at the following 3 time points: -0.5, 2.0, 3.0 to provide various measures and 
correlations with behavioral tasks and correlations with serum levels.  
  
4. Aims & Hypotheses:  
 
Specific Aim 1: Assess PREG on levels of ALLO in a dose-finding design. Relative to PBO, 
PREG will dose-dependently increase and normalize ALLO levels in individuals high in PSI such 
that it will be comparable to Matched Healthy Controls (MHC) (Hypothesis 1A).  
 
Specific Aim 2: Examine PREG on attentional bias to social threats and depressive 
symptomatology in individuals who are high in PSI. Relative to PBO, PREG will reduce 
depressive symptomatology and attentional bias to social threats and improve intention 
understanding and perception of others in individuals high in PSI (Hypothesis 2A). Hypothesis 
2B: In PSI and MHC, depressive symptomatology and attention to social threats will correlate 
negatively with ALLO levels.  
 
5. Duration of the study: The total duration of the entire study on campus is between 4 
and 4 ½ hours maximum.  
 
6. Location of the study:  
The entire study will be performed at the University of Chicago Department of Psychiatry and 
the University of Chicago Center for Cognitive and Social Neuroscience Center’s High-
Performance Electrical Neuroimaging (HPEN) Laboratory (940 E. 57th Street, 4th Floor, Chicago, 
IL 60637) on a 128-channel EGI system with 1000 HZ sampling rate. 
 
 


EEG and Pregnenolone Project 
 
Protocol Narrative 
8 
7. RESEARCH METHODS 
The Approach 
This project will comprise a randomized, placebo- controlled, between-subjects design, 
where we will couple a validated behavioral paradigm on attention to social threats with an acute 
pharmacological challenge with oral pregnenolone (PREG) or placebo (PBO) in subjects high in 
PSI and test behavioral responses and neuro-active steroid levels prior and after study oral drug 
administration. In the present project, 224 PSI subjects will be randomized to a single oral dose 
of PREG 400mg (n=112), or placebo (PBO, n=112) to ascertain dose of administration. In this 
project, participants will attend a single laboratory visit. During this single session, behavioral 
responses and subjective feelings will be tested at two time points (once before and once after). 
Neuro-active steroids will be measured from blood and saliva at several points to ascertain they 
correlate. A group of Matched Healthy Controls (MHC) who are low in PSI (n=12) and will not 
receive PREG but will otherwise complete all questionnaires of the study. Participants will be 
recruited from the University of Chicago and in the community.  
 
All participants must be 1) Male; 2) Aged 21-80 (inclusive); 3) High in PSI (PSI > 42, 
except for controls who should have a score ≤ 42); 4) Do not meet Mini-International 
Neuropsychiatric Interview (M.I.N.I) criteria for psychiatric illness (except untreated major 
depressive disorder); and 5) BMI <30 (as ALLO levels are higher in obese than non-obese 
individuals). Key Exclusion Criteria: Female, as ALLO levels vary as a function of the menstrual 
cycle; 2) Aged < 21 or > 80; 3) Low in PSI (PSI < 42, except for controls)); 4) meet M.I.N. I 
criteria for psychiatric illness, besides untreated major depressive disorder; 5) Uncorrected 
vision; 6) Medical history of cancer; 7) Medical history of condition that might be made worse 
by exposure to estrogen or testosterone; 8) Recent steroid use; 9) Currently taking psychotropic 
medication; 10) History of seizures, neurological disorders; 11) History of TBI with loss of 
consciousness and/or with current cognitive impairment related to TBI; 12) Under hormonal 
therapy (including, but not limited to, testosterone); 13) Any unstable medical illnesses; 14) 
Lifetime history of bipolar disorder, schizophrenia, or psychotic disorder; 15) Current or recent 
(past 3 months) substance abuse or dependence; 16) Currently taking any medications that 
have/may have unfavorable interactions with Pregnenolone; 17) History of irregularities of heart 
rhythm, or heart palpitations; 18) obesity (defined as BMI>30); 19) illegal drug use as 
determined by urine drug screen. 
Rationale: The recruitment and random assignment of young adults high in PSI to the 
PREG and PBO conditions allow us to ascertain the effects of PREG on PSI, depressive 
symptoms, and attentional biases for social threats. In addition, the recruitment of participants 
between the ages of 21 and 80 years will allow us to compare emotional and neurobiological 
findings across groups without the confounder of age effects.  
 
Upon receipt of written consent, subjects will fill out self-report questionnaires and undertake 
practice on our behavioral paradigm.  
During the visit, the following will occur: 
• The subject will complete several questionnaires, including questions about 
perceived social isolation and questions about his mood. 
• The subject will do a visual task on a computer. 
• If the subject has low perceived isolation, the study drug will NOT be given.  
• The subject will be asked to provide blood samples throughout the visit so that we 


EEG and Pregnenolone Project 
 
Protocol Narrative 
9 
can see how his blood hormones change at different times. The experimenter will 
draw blood from the subject’s arm three times: 1) 30 minutes after your arrival at 
the high-performance electrical neuroimaging laboratory, 2) one 2 and 30mn later 
and 3) again an hour later. About 1 teaspoon of blood will be taken each time. 
• The subject will also be asked to provide saliva samples during the study at the 
same three times: 1) 30 mn after your arrival at the high-performance electrical 
neuroimaging laboratory, 2) one 2 and 30mn later and 3) again one an hour later. 
About 1 teaspoon of saliva will be taken each time. We ask the subject to provide 
saliva samples so that we can see how the samples are related to behavioral tasks 
and how the subject is feeling at different times in the study. 
• The subject will watch a 2-hour-long relaxing movie in a quiet and relaxing 
environment. 
 
Two hours after the subject takes the pill (drug or placebo), the following will occur: 
• The subject will do the exact same behavioral visual task on a computer . Control 
subjects will perform the same tasks at the same time, except they will not take 
any pills.  
• The subject will complete the same questionnaires again. 
• The subject will wait for 30 minutes in a relaxing and quiet environment. 
• The subject will be given a parking voucher or $5 for public transportation and a 
$60 monetary compensation for participating in the study. 
 
Estimated Duration of Visit: Between 4 Hours and 4 ½ hours 
 
 
In the event suicidal ideation or similar events take place during the study, the subject 
will be removed from the study and referred to the appropriate clinical resources. 
 
 
C.2.2. Behavioral Paradigms: Subjects will be asked to perform a paradigm our lab has used to 
investigate social interactions on which PSI-related attentional biases may occur i.e., body 
language observation, facial expression, and grasping actions: Body language: As in S. 
Cacioppo, Bangee et al. (2014)’s study, participants will be asked to view a total of 2 blocks of 
pictures of body language with each block containing the 28 pictures. Each picture from each 
category will be presented once in a block. The order of the blocks will be randomized for each 
participant, but the order of the pictures within the block will be pre-determined with no more 
than three consecutive trials of the same picture-type presented. Prior to each trial, participants 
will view a white fixation cross on a black background that varied between 500 and 1500 ms. 
Each picture will be presented in color for 1000 ms, followed by a response slide that required a 
button press to move onto the inter-stimulus interval (ISI) for 500 ms. Participants will view 
threat and non-threat body language;  
C.2.3. Psychological measures: Along with standardized assessments of symptom severity and 
mood/emotional state, subjects will complete the following measures, at multiple time points 
(e.g., before and after drug administration): The UCLA-R scale to measure perceived social 
isolation; Steptoe’s questionnaire on objective social isolation; Hospital Anxiety and Depression 
Scale; Life satisfaction scale; and Demographics. 


EEG and Pregnenolone Project 
 
Protocol Narrative 
10 
C.2.4. Study Measures:  Along with various psychological measures, subjects will complete: the 
Edinburgh Handedness Inventory, Big Five Personality trait (short), PSI Scale, Self-esteem 
scale, Wong-Baker Faces Pain scale, Cacioppo Faces Social Pain scale, Paranoia Scale, Life 
Satisfaction Scale, Relationship/Marital Satisfaction Scale, Inclusion of the Other Scale, 
Columbia Suicide Severity Rating Scale, MINI, and the body image scale.  
C.2.5. Drug administration: As in Sripada et al.’s 2013, study drug (PREG) and placebo (PBO) 
identical in appearance will be obtained from Belmar Pharmacy (Lakewood, CO), which 
provides certificates of analysis. A member of the research team (who is not involved in the data 
analyses) will randomly assign eligible subjects to the treatment group (PREG 400mg) or to the 
control group (PBO) through the use of a computerized random number generator. Participants 
will be blind.  
C.2.6. Neurosteroid Analyses: To compare ALLO results with Sripada et al.’s 2013, basal serum 
levels will also be taken (once prior to drug administration and once two hours after oral 
administration of the drug study) and analyzed using a gold-standard in the literature: a gas-
chromatographic mass-spectrometric (GC-MS) approach. Serum levels of pregnenolone, 
progesterone, 5alpha-DHP and ALLO and pregnanolone (ALLO's steroisomer and GABA-
active) will be measured. As in Majewaska et al (2014), saliva samples will be analyzed using 
the same gold standard GC-MS approach in ALLO literature i.e., a method that allow for 
accurate measurement in the femtomolar range of specific neurosteroids. We will ensure that 
participants will refrain from smoking, eating, drinking alcoholic, caffeinated, or juicy 
beverages, and brushing teeth at least one hour before the first saliva sample and between saliva 
samples. 
C.2.7. General Statistical approach: 
Demographic and self-report psychological measures: Statistical analyses for demographic and 
self-report measures will be computed using SPSS software. Prior to inferential analyses, 
descriptive statistics, including distributions, means, standard deviations, skewness, and kurtosis 
will be generated. Data will also be examined for the pattern and mechanism of missing data. 
Continuous data will be tested for normality and homogeneity of variance. Potential differences 
between the study groups in terms of demographic and behavioral measures will be explored using 
multivariate analysis of variance (MANOVA) or appropriate non-parametric tests as appropriate. 
The overall significance level for these analyses will be at 5% using two-tailed tests and effect 
sizes and confidence intervals will be reported. In addition, scores at self-report questionnaires will 
be analyzed via a 2 (Drug Type: PREG 400mg, or PBO) x 2 (time: before, after) repeated measures 
ANOVA to assess for main effects and interaction effects.  
Behavioral paradigms: Statistical analyses will be computed using SPSS software. Reaction 
times and performance data will be screened and any outliers will be removed based on each 
participant’s trial-by-trial data.  A trial will be removed if it differed by 3 standard deviations 
above or below the participant’s mean. Prior to inferential analyses, descriptive statistics, 
including distributions, means, standard deviations, skewness, and kurtosis will be generated. 
Data will also be examined for the pattern and mechanism of missing data.  
• For the body language paradigm: A 2 (Drug Type: PREG 400mg, or PBO) x 2 (type of 
stimuli: social, non-social) x 2 (nature of the stimuli: threat, non-threat) repeated-
measures ANOVA will be performed on the reaction times and valence ratings to assess 
for main effects and interaction effects. P values, confidence interval, and effect sizes will 
be reported.  
  


EEG and Pregnenolone Project 
 
Protocol Narrative 
11 
C.2.6. Power Analysis: Using G* power calculation software (Version 3.1.9.2; © Franz Faul, 
Edgar Erdfelder, Albert-Georg Lang, and Axel Buchner, 2006, 2009) for a within-between 
interaction in a repeated measures ANOVA, a total sample size of 36 for three groups will yield 
95% power to detect a significant difference, with alpha = 0.05 and an effect size Cohen’s d of 
0.35 in the present project. 
 
Note: The hormone tested in saliva and blood have the same origin from adrenals glands and 
gonads. Here we want to establish a correlation within the same subjects among the levels of the 
same neuro-active steroid determined in the blood and the saliva. We expect the hormone levels 
measured in saliva and in blood to be different in amount but to correlate. 
 
Saliva samples will be analyzed using the same gold standard GC-MS approach in ALLO 
literature i.e., a method that allow for accurate measurement in the femtomolar range of specific 
neurosteroids. We will ensure that participants will refrain from smoking, eating, drinking 
alcoholic, caffeinated, or juicy beverages, and brushing teeth before each saliva sample. 
 
 
7. Special Precautions:  
Pregnenolone side effects, danger, risk, and the harm it can cause 
Overstimulation and insomnia – 
Irritability, anger or anxiety –  
Acne can occur due to the probable conversion of this hormone into androgens 
Headaches are possible with high dosages or low dosages used over several days or weeks. 
Possible scalp hair loss if used daily for prolonged periods. Pregnenolone converts into DHEA, 
which in turn converts into testosterone and possibly on to DHT. It can also be converted into 
progesterone. 
Irregularities of heart rhythm, Heart Palpitations, even on as low a dose as 5 mg. This can be 
serious in the elderly or those with heart rhythm disturbances.  
Unknown effects on the thyroid gland or other organs and tissues. 
 
Special Precautions & Warnings: 
Pregnancy and breast-feeding: Although there is not enough known about the use of 
pregnenolone during pregnancy and breast-feeding, we’ll avoid this risk by testing male 
participants only. 
  
Hormone-sensitive condition such as breast cancer, uterine cancer, ovarian cancer, 
endometriosis, or uterine fibroids might have an interaction with pregnenolone: We’ll 
exclude participants with any history of condition that might be made worse by exposure to 
estrogen.  
 
8. Participants: 
 
We will recruit 224 men (between 21 and 80) high in PSI and 12 Matched Healthy 
Controls (MHC) who are low in PSI. 
 
9. Type and Number of Experimental Subjects: 
 
We expect to collect data from a total of 36 subjects (between 21 and 80).  


EEG and Pregnenolone Project 
 
Protocol Narrative 
12 
 
10. Potential Risks and Benefits: 
 
The study will offer no direct benefits (besides monetary benefits and potential 
improvement of sexual desire) to participants. The questionnaires and behavioral task also 
present minimal risks, which may include boredom and fatigue from looking at pictures for a few 
minutes and anxiety or discomfort or distress related to responding to questionnaires.  
 
11. CONTRAINDICATIONS:  
• 
Estrogens interacts with PREGNENOLONE 
Taking estrogen along with pregnenolone might cause too much estrogen to be in the body. 
 
Some estrogen pills include conjugated equine estrogens (Premarin), ethinyl estradiol, 
estradiol, and others. 
    Progestin interacts with PREGNENOLONE 
Progestins are a group of hormones. Taking other hormones along with progesterone pills 
might cause too much hormones in the body. This could increase the effects and side effects 
of hormone pills. 
• 
Testosterone interacts with PREGNENOLONE 
Taking pregnenolone along with a testosterone pill might cause too much testosterone in the 
body. This might increase the chance of testosterone side effects. 
 
12. Monitoring of Safety: 
 
A researcher will be present with participants during the duration of the experiment. 
While participants are in a separate room sheltered, researchers will monitor participants’ well-
being via cameras and microphones within this room. Participants will have the ability to 
communicate with researchers through these microphones and may opt out of participation at 
any time. Participants will also be provided with the IRB’s contact information on the consent 
form, and we will contact IRB should any adverse effects occur. 
Regarding pregnenolone’s side effects:  Subjects will be directed to call a member of the study 
team if they believe they are experiencing any side effects within the 12 hours following the end 
of the study.  
 
13. Payment:  
Participants will receive the $60 monetary compensation (Internal Fundings/No Fund) for 
their participation in the entire study. If participants should decide to opt out of participation after 
the beginning of the study, their participation would be pro-rated ($15 per hour).  
 
 
14. Informed Consent: 
 
We are asking to waive first consent form to do a brief phone interview and see whether 
the participants are eligible. Then the participants will come to the University of Chicago and 
read, understand and sign the written consent form attached in this IRB application. Participants 
must acknowledge understanding of procedures, risks, and benefits by signing this consent form 
before the study can proceed. 
 


EEG and Pregnenolone Project 
 
Protocol Narrative 
13 
 
 
15. Confidentiality: 
 
De-identified data will be stored in locked drawers or cabinets or on password-protected 
computers within the HPEN laboratory or on password protected University of Chicago server, 
such as UChicago Box. Data may be used in publications, but no personally identifiable 
information will be disseminated outside of researchers included in this protocol. 
 
16. Recruiting Methods:  
 
Subjects will be recruited via Flyers posted on Campus, sona or websites, such as 
craigslist. 
 
17. Primary Physician Notification:  
Dr. Jon Grant, M.D.  
 
18. Anticipated Coordination between Inter-Departmental Faculty: 
 
Stephanie Cacioppo, Ph.D., Jon Grant, M.D., and Royce Lee, M.D. are all members of 
the Department of Psychiatry and Behavioral Neuroscience. John Cacioppo is the Director of the 
Center for Cognitive and Social Neuroscience. These researchers will coordinate extensively on 
this project. 
 
19. Pregnancy Test:  N/A. The present research only includes male participants.  
 
20. Drug Test:  
 
Marijuana use may interact with pregnenolone. The drug can antagonize cannabinoid 
receptors in the brain and if subjects have been exposed to marijuana over a long period of time 
it may negate the effect of the study drug. Because of this, subjects will be asked to provide a 
urine sample at the beginning of the visit (after signing the informed consent). This will be used 
to screen for illegal drugs. The screening must be negative in order for the subject to continue 
participating in the study. 
 
21. References to Justify Study: 
 
Amin. Z., Mason, G.F., Cavus, I., Krystal, J.H., Rothman, D. L., Epperson, C.N. (2006). The 
interaction of neuroactive steroids and GABA in the development of neuropsychiatric disorders 
in women. Pharmacol Biochem Behav, 84:635–643. 
 
Bangee, M., Harris, R. A., Bridges, N., Rotenberg, K. J., Qualter, P. (2014). Loneliness and  
attention to social threat in young adults: Findings from an eye-tracker study. Personality and  
Individual Differences, 63:16-23. doi: 10.1016/j.paid.2014.01.039. 
 
Buckner, J. D., DeWall C. N., Schmidt, N. B., Maner, J. K. (2010). A tale of two threats: Social 
anxiety and attention to social threat as a function of social exclusion and non-exclusion threats. 
Cognitive Ther Res. 34:449-455. 
 


EEG and Pregnenolone Project 
 
Protocol Narrative 
14 
Button, K., Ioannidis, J., Mokrysz, C., Nosek, B., Flint, J., Robinson, E., Munafò, M. (2013). 
Power failure: why small sample size undermines the reliability of neuroscience. Nature reviews: 
Neuroscience, 14:365–376. doi:10.1038/nrn3475. 
 
Cacioppo, S. (2016) What happens in your brain during mental dissociation? A question towards 
an unifed sense of self. Current Behavioral Neuroscience Reports. 3:1-9.  doi: 10.1007/s40473-
016-0063-8. 
 
Cacioppo, S., & Cacioppo, J. T. (2015). Why may allopregnanolone help alleviate loneliness? 
Medical Hypotheses, doi: http://dx.doi.org./10.1016/j.mehy.2015.09.004. 
 
Cacioppo, S., Capitanio, J. P., Cacioppo, J. T. (2014). Toward a neurology of 
loneliness. Psychological Bulletin, 140:1464-1504. doi: 10.1037/a0037618. 
 
Cacioppo, S., Frum, C., Asp, E., Weiss, R. M., Lewis, J. W., Cacioppo, J. T. (2013). A 
quantitative meta-analysis of social rejection. Scientific Reports, 3:2027. doi: 
10.1038/srep02027. 
 
Cacioppo, J. T., Cacioppo, S., Dulawa, S., Palmer, A. (2014). Social Neuroscience and its 
potential contribution to psychiatry. World Psychiatry, 13:131-139. doi: 10.1002/wps.20118. 
 
Cacioppo, J.T. & Cacioppo, S. (2014). Social relationships and health: The toxic effects of 
perceived social isolation. Social and Personality Psychology Compass, 8:58-72. doi: 
10.1111/spc3.12087.  
 
Cacioppo, J.T., Cacioppo, S., Capitanio, J. P., Cole, S. W. (2015a). The neuroendocrinology of 
social isolation. Annual Review of Psychology, 66:9.1-9.35.  
 
Cacioppo, S., Grippo, A. J., London, S., Goossens, L., Cacioppo, J. T. (2015c). Loneliness: 
Clinical Import and Interventions. Perspectives on Psychological Science. 10:238-49. doi: 
10.1177/1745691615570616. 
 
Cacioppo, J. T., Cacioppo, S., Cole, S. W., Capitanio, J. P, Goossens, Boomsma, D. I. (2015b). 
Loneliness Across Phylogeny and a Call for Comparative Studies and Animal 
Models. Perspectives on Psychological Science, 10:202-212. 
 
Cacioppo, J. T., Patrick, B. (2008). Loneliness: Human nature and the need for social connection. 
New York: W. W. Norton & Company. 
 
Carleton, R. N., McCreary, D. R., Norton, P. J., Asmundson, G. J. G. (2006). Brief fear of 
negative evaluation scale-revised. Depression and Anxiety, 23:297–303.  
 
Crowley, S. K., O'Buckley, T. K., Schiller, C. E., Stuebe, A., Morrow, A.L., Girdler, S.S. (2016). 
Blunted neuroactive steroid and HPA axis responses to stress are associated with reduced sleep 
quality and negative affect in pregnancy: a pilot study. Psychopharmacology (Berl). 233:1299-
310. doi:10.1007/s00213-016-4217-x. 


EEG and Pregnenolone Project 
 
Protocol Narrative 
15 
 
Diener, E., Emmons, R. A., Larsen, R. J., Griffin, S. (1985). The Satisfaction with Life Scale. 
Journal of Personality Assessment, 49:71-75. 
 
Egidi, G., Shintel, H., Nusbaum, H.C., Cacioppo, J.T. (2008). Social isolation and neural 
 correlates of attention control. 20th Annual Meeting of the Association for Psychological 
 Science; Chicago, IL. 
 
Girdler SS, Beth Mechlin M, Light KC, Leslie Morrow A. (2006). Ethnic differences in 
allopregnanolone concentrations in women during rest and following mental stress. 
Psychophysiology, 43:331-6. PubMed PMID: 16916428. 
 
Gross, J.J., & John, O.P. (2003). Individual differences in two emotion regulation processes: 
Implications for affect, relationships, and well-being. Journal of Personality and Social 
Psychology, 85:348-362.  
 
Klatzkin, R.R., Morrow, A.L., Light, K.C., Pedersen, C.A., Girdler, S.S. (2006). Histories of 
depression, allopregnanolone responses to stress, and premenstrual symptoms in 
women. Biol Psychol, 71:2-11. 
 
Bobau, R. Sniezek, J., Zack, M. M., Lucas, R.E., Burns, A. (2010). Well-being assessment: An 
evaluation of well-being scales for public health and population estimates of well-being among 
US adults. Applied Psychology: Health and Well-being, 2:272-297. 
Doi:http://dx.doi.org/10.1111/j.1758-0854.2010.01035.x 
 
Leary MR. (1983). A brief version of the fear of negative evaluation scale. Personality and 
Social Psychology Bulletin, 9: 371–375. 
 
Lester, P. B., Harms, P. D., Herian, M. N., Krasikova, D. V., Beal, S. J. (2011). The 
Comprehensive soldier Fitness program evaluation. Report #3: Longitudinal analysis of the 
impact of Master Resilience training on self-reported resilience and psychological health data. 
Retrieved from http://dma.wi.gov/dma/news/2012news/csf-tech-support.pdf 
 
Marx, C. E., Keefe, R. S., Buchanan, R. W., Hamer, R. M., Kilts, J. D., Bradford, D. W., et al. 
(2009). Proof-of-Concept Trial with the Neurosteroid Pregnenolone Targeting Cognitive and 
Negative Symptoms in Schizophrenia. Neuropsychopharmacology.  
 
Marx, C. E., Shampine, L. J., Khisti, R. T., Trost, W. T., Bradford, D. W., Grobin, A. C., et al. 
(2006). Olanzapine and fluoxetine administration and coadministration increase rat hippocampal 
pregnenolone, allopregnanolone and peripheral deoxycorticosterone: implications for therapeutic 
actions. Pharmacol Biochem Behav, 84:609–617. [PubMed: 16996120] 
 
Nelson, M., Pinna, G. (2011). S-norfluoxetine infused into the basolateral amygdala increases 
allopregnanolone levels and reduces aggression in socially isolated mice. Neuropharmacology, 
60:1154–1159. 


EEG and Pregnenolone Project 
 
Protocol Narrative 
16 
 
Oldfield, R. C. (1971). The assessment and analysis of handedness: the Edinburgh inventory. 
Neuropsychologia, 9:97–113. 
 
Oosterhof, N. N., Todorov, A. (2008). The functional basis of face evaluation. Proceedings of the 
National Academy of Sciences of the USA, 105 11087-11092.  
 
Ossewaarde, L., Hermans, E. J., van Wingen, G. A., Kooijman, S. C., Johansson, I. M., 
Backstrom, T., et al. (2009). Neural mechanisms underlying changes in stress-sensitivity across 
the menstrual cycle. Psychoneuroendocrinology, 35:47–55. [PubMed: 19758762] 
 
Pibiri, F., Nelson, M., Guidotti, A., Costa, E., Pinna, G. (2008). Decreased corticolimbic 
allopregnanolone expression during social isolation enhances contextual fear: A model relevant 
for posttraumatic stress disorder. Proc Natl Acad Sci U S A., 105:5567–5572. [PubMed: 
18391192] 
 
Pinna, G.  (2010). In a mouse model relevant for post-traumatic stress disorder, selective brain 
steoidogenic stimulants (SBSS) improve behavioral deficits by normalizing allopregnanolone 
biosynthesis.Behavioral Pharmacology, 21:438–450. 
 
Pinna, G., Costa, E., Guidotti, A. (2009). SSRIs act as selective brain steroidogenic stimulants 
(SBSSs) at low doses that are inactive on 5-HT reuptake. Curr Opin Pharmacol, 9:24–30. 
[PubMed: 19157982] 
 
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selectively increase brain neurosteroid content at doses that are inactive on 5-HT reuptake. 
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traumatic stress disorder. J Neuroendocrinol, 24:102–116. [PubMed: 21981145] 
 
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ICF_001.pdf: 
Version Date: 9/30/2016 
Page 1 of 7
The UNIVERSITY OF CHICAGO
The Division of the Biological Sciences  The University of Chicago Medical Center
CONSENT/AUTHORIZATION BY SUBJECT FOR PARTICIPATION IN A 
RESEARCH PROTOCOL
Protocol Number: IRB16-0834
Name of Subject:  
STUDY TITLE:  Effects of Pregnenolone on Perceived Social Isolation
Doctors Directing Research: Dr. Stephanie Cacioppo & Dr. Jon Grant
Address: University of Chicago Medical Center
   Department of Psychiatry
   5841 South Maryland Avenue, MC 3077
Telephone Number: 773-702-6983
You are being asked to participate in a research study. A member of the research team 
will explain what is involved in this study and how it will affect you. This consent form 
describes the study procedures, the risks and benefits of participation, as well as how your 
confidentiality will be maintained. Please take your time to ask questions and feel comfortable 
making a decision whether to participate or not. This process is called informed consent.  If you 
decide to participate in this study, you will be asked to sign this form. 
WHY IS THIS STUDY BEING DONE?
The purpose of this study is to investigate the effects of pregnenolone on perceived social 
isolation, such as feelings of loneliness. Pregnenolone is a hormone that we believe might 
work to alleviate loneliness because of the way it works in the brain. It interacts with a 
neurosteroid called allopregnanolone, which, when impaired, has been associated with 
aspects of perceived social isolation.  Another purpose of this study is to investigate how 
other feelings (such as life satisfaction and anxiety) change after a one time intake of 
pregnenolone (400mg) or after a one time intake of a placebo (sugar pill).
Pregnenolone is being used as an experimental drug for this study. This means that 
pregnenolone is not approved by the Food and Drug Administration for reducing the 
symptoms of perceived social isolation.
HOW MANY PEOPLE WILL TAKE PART IN THE STUDY?
About 224 people with high perceived social isolation and 12 people with low perceived 
social isolation will take part in this study at the University of Chicago.
WHAT IS INVOLVED IN THE STUDY?
The study will last about  4 to 4 ½ hours and includes one office visit. During the visit, if 
you have high perceived social isolation, you will be randomly assigned to a study drug 
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administration group (a group who takes pregnenolone 400mg) or the control group 
(group who takes the placebo). Whether you receive the study drug or the placebo is 
based on a 50/50 chance, like flipping a coin. In all, 112 subjects will receive 
pregnenolone 400mg, and 112 subjects will receive the placebo. 
During the visit, you will be asked to fill out a series of questionnaires (e.g., 
demographics, questions about perceived social isolation, and questions about your 
mood) and do a behavioral visual task on a computer while your responses and reaction 
times will be recorded.
During the visit, the following will occur:

The study will be discussed with you and you will be asked to sign this consent 
form.

A review of your medical history and your medications will be completed.

A review of your family history, a review of family medical issues and psychiatric 
issues will be discussed with you.

You will be asked to give a urine sample that will be tested for illegal drug use 
(including marijuana). This test must be negative in order to participate in the 
study.

You will complete several questionnaires, including questions about perceived 
social isolation and questions about your mood.

You will do a visual task on a computer.

If you have high perceived isolation, the study drug will be given to you (either 
pregnenolone 400mg, or placebo) and you will be instructed on how to take it 30 
minutes after you arrive at the high-performance electrical neuroimaging (HPEN) 
laboratory. 

You will be asked to provide blood samples throughout the visit so that we can 
see how your blood hormones change at different times after taking the 
pregnenolone or placebo. The experimenter will draw your blood from your arm 
three times: 1) 30 minutes before you take the study drug, 2) 2 hours and 30 
minutes after taking the study drug, and 3) again an hour later. About 1 teaspoon 
of blood will be taken each time.

You will also be asked to provide saliva samples during the study at the same 
three times. About 1 teaspoon of saliva will be taken each time. We ask you to 
provide saliva samples so that we can see how the samples are related to 
behavioral tasks and how you are feeling at different times in the study.

You will watch a 2 hour-long relaxing movie in a quiet and relaxing environment.
Two hours after you take the pill (drug or placebo) , the following will occur:

You will do the exact same behavioral visual task on a computer 

You will complete the same questionnaires again.

You will wait for 30 minutes in a relaxing and quiet environment.

Estimated Duration of Visit: 4 to 4 1/2 Hours
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Behavioral visual task: You will be shown some images and/or words on a computer. 
No pictures involving nudity will be presented. However, some of these images may be 
stressful, but should not be overwhelming. If you feel uncomfortable at any time, please 
alert the study staff immediately.
During this study, Dr. Stephanie Cacioppo and her research team will collect information 
about you for the purposes of this research. This information includes name, date of birth, 
telephone number, e-mail address, demographic information, and the results of your 
study-related tests. Your behavioral data will be represented by a code number in the data 
field where a name would ordinarily go. Data from this study may be used in research 
publications or presentations. Your name and other identifying information will NOT be 
part of this data set. 
In the event suicidal ideation or similar events take place during the study, you will be 
removed from the study and referred to the appropriate clinical resources.
HOW LONG WILL I BE IN THE STUDY?
We think you will be in the study for 4 to 4 ½ hours, where you will take the study drug 
or placebo once. There is no long-term follow-up after you stop the study.
Dr.  Cacioppo may decide to take you off the study without your consent if:

You are unable to meet the requirements of the study;

Your medical condition changes;

The study drug is no longer available;

New information becomes available that indicates that participation in this study is 
not in your best interest; or

If the study is stopped.
WHAT ARE THE RISKS OF THE STUDY?
The most common side effects observed in people taking the study drug pregnenolone 
include:

Anxiety

Insomnia

Irritability

Headaches

Acne

Scalp hair loss
There is a possibility that you may have heart palpitations or an irregular heart rhythm. If 
this happens, please let the study doctor know immediately. If you have a history of any 
heart problems, you are not eligible to participate in this study. 
 
The study team will also ask you questions about your mood and behaviors. These 
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questions may make you feel uncomfortable. If at any time you would like to stop the 
interview, please let a member of the study staff know. 
There may be other risks that could arise which are not reasonably foreseeable. If new 
information becomes available which could influence your willingness to continue, this 
new information will be discussed with you.
ARE THERE ANY BENEFITS TO TAKING PART IN THE STUDY?
If you agree to take part in this study, there may or may not be direct medical benefit to 
you. We hope the information learned from this study will benefit other individuals with 
high perceived social isolation in the future.
WHAT OTHER OPTIONS ARE THERE?
Participation in this study is voluntary. An alternative option to participating in the study 
is psychotherapy for perceived social isolation. The decision whether or not you wish to 
participate in this study will not affect your care at the University of Chicago Medical 
Center.
WHAT ARE THE COSTS? 
Clinical services provided during a clinical trial are either research-related or related to 
usual medical care. Research-related services are done to complete the research and the 
costs are not the responsibility of you or your insurance. 
The costs that are considered research-related for this study may include any additional 
laboratory tests, the study drug and placebo, physician visits, imaging, procedures or 
other clinical services that are dictated by the research protocol and only required because 
you are part of this study.  
Usual medical care costs include any and all services that are considered medically 
necessary for your disease and would be done even if you were not part of this research 
study. This may include laboratory tests, physician visits, imaging, procedures, and other 
clinical services that your physician orders for your routine care.  The cost of this usual, 
ongoing medical care will be the responsibility of you or your insurance, and may include 
deductibles and co-payments. Similarly, this care will be subject to all the same 
requirements and restrictions of your insurance. 
If you have questions about whether specific clinical services are research related or 
usual medical care, please speak to your physician or research contact person.
If you suffer an unanticipated injury as a direct result of this research and require 
emergency medical treatment, the University of Chicago Medical Center will provide 
such treatment at the University of Chicago Medical Center at no cost to you.  You must 
notify Dr. Cacioppo or Dr. Grant as promptly as possible after your injury in order to 
receive this care.  An injury is “unanticipated” if it is not one of the known effects of a 
study drug, medical device or procedure, and is not the result of your disease or 
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condition. The costs of any non-emergency care for such an injury will be billed to you or 
your insurance in the ordinary manner.  If you think that you have suffered a research 
related injury, you must let Dr. Cacioppo or Dr. Grant know right away.
WILL I BE PAID FOR MY PARTICIPATION?
You will receive $60 monetary compensation for your participation in the study at the 
end of the visit. You will also receive a parking voucher or $5 for public transportation at 
the end of the visit. If the study has to be interrupted before the end of your visit, your 
compensation will be pro-rated at $15 per hour. 
WHAT ABOUT CONFIDENTIALITY?
Study records that identify you will be kept confidential. All of the data will be kept in a 
secure computer server and in locked filing cabinets only accessible to the research team.   
The data collected in this study will be used for the purpose described in the form.  By 
signing this form, you are allowing the research team access to your medical records, 
which include Protected Health Information.  Protected Health Information (PHI) 
consists of any health information that is collected about you, which could include your 
medical history and new information collected as a result of this study.  The research 
team includes the individuals listed on this consent form and other personnel involved in 
this study at the University of Chicago. However, our study records will not include any 
identifiers. Your data will be thus de-identified using a coding system. Your behavioral 
data and EEG scan will be performed with a code number in the data field where a name 
would ordinarily go. Data from this study may be used in research publications or 
presentations or a registry shared between University of Chicago investigators. Your 
name and other identifying information will NOT be part of this data set. 
Your records may be reviewed by federal agencies whose responsibility is to protect 
human subjects in research including the Food and Drug Administration (FDA) and 
Office of Human Research Protections (OHRP).  In addition, representatives of the 
University of Chicago, including the Institutional Review Board, a committee that 
oversees the research at the University of Chicago, may also view the records of the 
research.  If your research record is reviewed by any of these groups, they may also need 
to review your entire medical record.
If health information is shared outside the University of Chicago, the same laws that the 
University of Chicago must obey may not protect your health information.
During your participation in this study, you will have access to your medical record. Dr. 
Cacioppo is not required to release to you research information that is not part of your 
medical record.
This consent form will be kept by the research team for at least five years. The study 
results will be kept in your research record and be used by the research team indefinitely. 
At the time of study completion, either the research information not already in your 
medical record will be destroyed or information identifying you will be removed from 
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study results.  Any research information in your medical record will be kept indefinitely.
Data from this study may be used in medical publications or presentations.  Your name 
and other identifying information will be removed before this data is used.  If we wish to 
use identifying information in publications, we will ask for your approval at that time.
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as 
required by U.S. Law. This Web site will not include information that can identify you. 
At most, the Web site will include a summary of the results. You can search this Web site 
at any time.
WHAT ARE MY RIGHTS AS A PARTICIPANT?
Taking part in this study is voluntary.  If you choose not to participate in this study, your 
care at the University of Chicago/University of Chicago Medical Center will not be 
affected. You may choose not to participate at any time during the study.  Leaving the 
study will not affect your care at the University of Chicago/University of Chicago 
Medical Center.
If you choose to no longer be in the study and you do not want any of your future health 
information to be used, you must inform Dr. Cacioppo in writing at the address on the 
first page.  Dr. Cacioppo may still use your information that was collected prior to your 
written notice. 
We will tell you about significant new information that may affect your willingness to 
stay in this study. 
You will be given a signed copy of this document. This consent form document does not 
have an expiration date.
WHOM DO I CALL IF I HAVE QUESTIONS OR PROBLEMS?
You have talked to a member of the study team about this study and you had the 
opportunity to ask questions concerning any and all aspects of the research.  If you have 
further questions about the study, you may call Dr. Cacioppo at (773) 702-6983. 
If you have a research related injury, you should immediately contact Dr. Cacioppo at 
(773) 702-6983 or Dr. Grant at (773) 834-1325. 
If you have any questions concerning your rights in this research study you may contact the 
Institutional Review Board, which is concerned with the protection of subjects in research 
projects.  You may reach the Committee office between 8:30 am and 5:00 pm, Monday 
through Friday, by calling (773) 702-6505 or by writing:  Institutional Review Board, 
University of Chicago, 5841 S. Maryland Avenue, MC7132, I-625 , Chicago, Illinois,  
60637.
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CONSENT
SUBJECT
The research project and the procedures associated with it have been explained to me.  
The experimental procedures have been identified and no guarantee has been given about 
the possible results. I will receive a signed copy of this consent form for my records.
I agree to participate in this study.  My participation is voluntary and I do not have to sign 
this form if I do not want to be part of this research study.
Signature of Subject:  
Date:  
Time:  
   AM/PM (Circle)
PERSON OBTAINING CONSENT
I have explained to___________________________ the nature and purpose of the study 
and the risks involved.  I have answered and will answer all questions to the best of my 
ability.  I will give a signed copy of the consent form to the subject.
Signature of Person Obtaining Consent:  
Date:  
Time:  
   AM/PM (Circle)
PRINCIPAL INVESTIGATOR/PHYSICIAN:
Signature of Investigator/Physician  
Date:  
Time:  
   AM/PM (Circle)
Amendment ID:IRB16-0834-AM014   Date Approved: 7/26/2019   Expiration Date: 6/10/2020