Clinical trial NCT05038878
Conditions: Mild Autonomous Cortisol Excess
Keywords: mild autonomous cortisol excess (MACE) adrenal adenomas postmenopausal women GnRH antagonist
Sponsor: Icahn School of Medicine at Mount Sinai
Start date: 2021-07-06; Completion date: 2022-06-24
Enrollment: 4 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this research study is to determine if treatment with Elagolix will improve body weight, waist circumference, muscle strength, cortisol secretion, blood glucose, cholesterol, and bone quality as well as mood and quality of life in a female patient with mild hypercortisolism from adrenal overproduction of cortisol. Many people with adrenal nodules, or non-cancerous growths in the adrenal glands, have mildly elevated cortisol levels. Cortisol is a hormone normally made by the adrenal glands. It is increasingly being recognized that even mild elevations in cortisol levels can negatively impact blood glucose levels, serum cholesterol levels, weight and other metabolic parameters. This can lead to an increase in risk for cardiovascular disease. The study team is trying to determine if the medication Elagolix might be an effective treatment for post-menopausal females with mild hypercortisolism. Elagolix is a medication used to treat a medical condition called endometriosis by decreasing the body's production of sex hormones. Growth of adrenal adenomas is thought to be driven by such sex hormones. Therefore, by decreasing production of these hormones, the study team hopes to treat hypercortisolism caused by adrenal adenomas.

Detailed description:

Arms: arm 1: Post-menopausal women with benign appearing adrenal adenomas, absence of clinical features of overt Cushing's signs or symptoms and MACE confirmed on either 24 hr urine free cortisol (UFC), late night salivary cortisol and/or abnormal dexamethasone suppression
Interventions: intervention 1: Elagolix
Intervention descriptions: intervention 1: Patients will be given Elagolix 200 mg orally twice daily for a total of 6 months

Protocol documents:
Prot_SAP_000.pdf: 
An Oral GnRH Antagonist to Treat Mild Autonomous Cortisol Excess (MACE) Due to
Adrenal Adenomas in Postmenopausal Women
PI: Dr. Alice C. Levine
NCT05038878
Document Date: Aug 2, 2018


CONFIDENTIAL 
Template: Investigator Initiated Study Agreement – 02AUG2018 
40,022 
EXHIBIT A 
PROTOCOL 
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Section 
1.0 
 General Information 
1.1 
Study 
Title: 
Pilot study of Elagolix for the treatment of autonomous cortisol secretion (ACS) 
due to adrenal adenomas in postmenopausal women (SA- 002509, Protocol # 
A19-745) 
1.2 
1.2 
Institution 
Name: 
Icahn School of Medicine at Mount Sinai Hospital 
1.3 
Investigat
or Contact 
Informatio
n: 
Alice C. Levine, MD
Alice.levine@mountsinai.org 
(212) 241-3422 
Contact: Regina Belokovskaya, DO (regina.belokovskaya@mountsinai.org) 
2.0 
Background Information 
2.1 
Rationale 
& 
Backgroun
d 
Informatio
n 
The rationale specifies the reasons for conducting the research in light of current 
knowledge.  It should include a well-documented statement of the need/problem that is 
the basis of the project, the cause of this problem and its possible solutions.  It should 
answer the question of why and what: why the research needs to be done and what will 
be its relevance.  Selected literature references critical to the study design, dosage 
selection, or rationale for the study should be cited, as appropriate. 
Increasingly, patients are found to have incidentally found adrenal adenomas on 
imaging performed for other purposes. The most common secretory syndrome 
in adrenal nodules is autonomous cortisol secretion (ACS) where patients lack 
the typical clinical stigmata of overt hypercortisolism (1). 
Exposure to even low levels of excess cortisol can result in long term metabolic 
and cardiovascular effects which may not be completely reversible.  Subclinical 
hypercortisolism due to adrenal incidentalomas has been shown in multiple, 
large retrospective studies to be associated with an increased prevalence of 
hypertension and type 2 diabetes mellitus (T2DM) and cardiovascular risk (2, 3, 
4, 5). Morelli et al. reported that cardiovascular event prevalence was higher in 
patients with subclinical hypercortisolism, regardless of age and the presence of 
T2DM (6).  Most notably, a study by Di Dalmazi et al. demonstrated increased 
mortality due to cardiovascular disease in patients with even mild cortisol 
excess due to adrenal adenomas (2).  Mild, chronic cortisol excess is particularly 
toxic to bone resulting in increased bone demineralization and increased risk of 
vertebral fractures (7,8). There are limited studies regarding outcomes after 
unilateral adrenalectomy or medical management to treat this disorder.  
A recent publication demonstrated that adrenalectomy for patients with 
adenomas resulting in ACS reduces the risk of vertebral fractures (9).  
      Current options for medical treatment of Cushing syndrome include 
steroidogenesis enzyme inhibitors suitable for all causes of CS (ketoconazole, 
metyrapone, the glucocorticoid receptor antagonist, mifepristone), agents to 
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suppress ACTH in Cushing’s disease, such as dopamine agonists and pasireotide, 
and the adrenolytic and steroidogenic enzyme inhibitor mitotane for adrenal 
cortical carcinomas that secrete cortisol.   Mifepristone is currently the only FDA 
approved medication for Cushing’s syndrome with the specific indication for the 
treatment of elevated blood sugar in patients with Cushing’s syndrome and type 
2 diabetes mellitus (24).  We recently completed a pilot study that 
demonstrates that Mifepristone treatment of ACS is associated with a 
statistically significant decrease in fasting glucose and insulin resistance as 
measured by HOMA-IR scores (25).   With various insurance policies it is 
sometimes difficult to get these medications approved. Often time, 
ketoconazole, though not FDA approved, may be the first one covered by the 
insurance. However side effects are common, with the most limiting one being 
elevation in LFTs with ketoconazole.   
     The incidence of adrenal adenomas and ACS is higher in women than 
men with peak incidence at ages 50-70.  In addition, several case reports have 
demonstrated luteinizing hormone/human chorionic gonadotropin receptor 
(LH/HCG-R) expression in adrenal secretory tumors in postmenopausal and 
pregnant females .  A report by Teo et al. described a post-menopausal and 2 
pregnant women with aldosterone-producing adrenal adenomas, each of which 
harbored activating mutations of CTNNB1, the gene encoding β-catenin. The 
mutations stimulate Wnt activation and cause adrenocortical cells to de-
differentiate toward their common adrenal-gonadal precursor cell type 
including the expression of  LH/hCGR and GATA-4 [10].  
The adrenals and the gonads share a common lineage during embryogenesis 
(adrenogenital ridge).  Adrenal cortex arises from the coelomic mesoderm of 
the urogenital ridge, and the medulla arises from neural crest tissue. We have 
recently demonstrated that adrenal adenomas overexpress LH/HCG-R and Gata-
4 (gonadal differentiation factor) (11).  As such, there is strong evidence that 
adrenal tumor development is at least partially driven by LH in postmenopausal 
women.  We also will present data at The Endocrine Society 2019 
demonstrating expression of LH/HCG-R in 24/24 adrenal adenomas derived 
from postmenopausal women (12). Such findings have also been seen in 
primate species.  Lasley et al demonstrated the presence of luteinizing 
hormone/gonadal chorionic gonadotropin receptors in the adrenal cortex of 
ovarectomized female rhesus macaque (13). Further corroborating our data, 
Saxenda and Seely demonstrated a positive correlation between serum LH 
levels and urinary free cortisol levels in postmenopausal women (14).  
As such, there is strong evidence that adrenal tumor development is at least 
partially driven by LH in postmenopausal women.  Most recently, Doroszko et al 
studied the effects of the GnRH antagonist cetrorelix acetate (CTX) on 
adrenocortical tumor cells from mouse and human subjects in vitro and in 
transgenic mice in vivo, demonstrating that CTX decreased cell viability and 
proliferation in vitro and tumor size in vivo (15).  
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Thus, we hypothesize that LH/HCG-R is a viable target for the treatment of ACS 
due to adrenal adenomas in postmenopausal women.  In this study, we propose 
the use of elagolix, an oral GnRH antagonist recently approved for the 
treatment of endometriosis, to treat ACS in postmenopausal women with 
adrenal adenomas. 
3.0 
Core Protocol 
3.1 
Study 
Objectives 
and 
Purpose 
Objectives should be simple (no complex) and specific (no vague). After the statement 
of the primary objective, secondary objectives may be mentioned 
The goal of this pilot study is to determine if treatment of postmenopausal 
women with adrenal incidentaloma and ACS with elagolix for 6 months  leads to 
a decrease in adrenal adenoma size, reduction in hypercortisolism leading to 
improvement in metabolic, bone, mood and quality of life measures.   
3.2 
Study 
Design 
This section is a concise overview of the study design and should include the following: 
●
Type of experimental design (observational or interventional, randomized 
block, crossover, etc.); 
●
Whether the study is controlled (treatments other than the test product and/or 
placebo); 
●
Description of the type/design of the study to be conducted (e.g., open-label, 
single or double-blind); 
●
A specific statement of the primary endpoints and the secondary endpoints, if 
any, to be measured during the study; and, 
●
The number of the study centers (single or multi-center). 
The number of study centers (single or multi-center) and the total number of subjects 
included in the study and how they will be assigned to treatment groups must be 
indicated.  When appropriate, state if the subjects will be stratified. 
This is a pilot, open-label, interventional study.  Subjects will be recruited from 
The Mount Sinai Adrenal Center, Mount Sinai Internal Medicine Associates 
(IMA) and Faculty Practice Associates (FPA).  A total of 12 patients will be 
enrolled and all patients enrolled will receive study drug. This will be a change-
from-baseline approach. 
Primary Endpoints:  To determine the effects of elagolix treatment on 1) adrenal 
adenoma size 2) cortisol secretion 3) metabolic parameters and 4) bone 
turnover markers and vertebral fractures rates between baseline and 6 months 
treatment.
Secondary Endpoints:  To determine the effects of elagolix treatment on mood 
and quality of life. 
3.3 
Inclusion 
Criteria 
Eligible post-menopausal women that have incidentally found adrenal 
adenomas with benign appearing characteristics on imaging (<4 cm, non-
contrast CT <10 HU and/or lipid rich and benign appearing on MRI), the absence 
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of anti-anabolic clinical features of overt Cushing’s signs (proximal muscle 
weakness, >three ecchymoses, hyperpigmented striaie)  and 2 of 3 of the 
following: 1) elevated 24 hr urine free cortisol (UFC) above the upper limit of 
normal (>50 mcg/24 hours) in at least two complete 24-hour tests and/or 2)  
late night salivary cortisol more than upper limit of normal in at least two tests 
and/or 3) an abnormal dexamethasone suppression defined as post 1mg 
dexamethasone suppression test serum cortisol concentration of >1.8 mcg/ml 
will be eligible for inclusion (2).    
Post-menopausal is defined as: clinic status of cessation of menses for 12 mo in 
a previously cycling woman and reflecting complete or nearly complete 
permanent cessation of ovarian function and fertility (26). 
Patients with osteoporosis can be included in the study. However, if they are 
receiving treatment with either antiresorptive medications (bisphosphonates, 
denosumab) or anabolic agents (teriparitide, abaloparatide or romosozumab) 
any bone related data will be excluded from their analysis. 
3.4 
Exclusion 
Criteria 
Subjects receiving medications for chronic medical problems that may interact 
with elagolix, untreated hypothyroidism or hypopituitarism, known pituitary 
disorder, dexamethasone or CRH in the week prior to testing, use of elagolix, 
ketoconazole, metyrapone or mifepristone for one month prior, or known 
allergy to elagolix. In addition patients will be excluded if they have poorly 
controlled hypertension (mean systolic BP >170 mm Hg or mean diastolic BP 
>110 mm Hg) at screening, poorly controlled diabetes mellitus (Hemoglobin A1C 
>12% at screening), abnormal liver test results (total bilirubin >1.5 x upper limit 
normal or elevated alanine aminotransferase or aspartate amino transferase 
>3X upper limit normal at baseline), severe renal insufficiency (GFR <= 29 
ml/min) at baseline.  Patients will be excluded if they use or plan to use 
somatostatin analogues (octreotide, lanreotide or pasireotide) or have used 
these drugs within 8 months prior to study start.  Patients with adrenal cortical 
carcinoma will also be excluded. Patients with a history of malabsorption will be 
excluded. Patients on HRT will be excluded. 
Elagolix is also a substrate of CYP3A and therefore should not be used 
concomitantly with drugs that are strong CYP3A inhibitors including: 
clarithromycin, telithromycin, nefazodone, itraconazole, ketoconazole, 
atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, 
tipranavir. 
Drug interactions of note (not Exclusion Criteria): Elagolix is also a substrate of 
CYP3A and therefore should not be used concomitantly with drugs that are 
strong CYP3A inhibitors including: clarithromycin, telithromycin, nefazodone, 
itraconazole, ketoconazole, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, 
ritonavir, saquinavir, tipranavir. Elagolix is also a substrate of organic anion 
transporting polypeptide (OATP) therefore the concomitant use of strong OATP 
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1B1 inhibitors (e.g., cyclosporine and gemfibrozil) is contraindicated as they may 
increase plasma concentrations of elagolix. 
Elagolix is a weak to moderate inducer of cytochrome P450 (CYP) 3A. Co-
administration with Elagolix may decrease plasma concentrations of drugs that 
are substrates of CYP3A (i.e. amlodipine and atorvastatin). Elagolix is a weak 
inhibitor of CYP 2C19. Co-administration with Elagolix may increase plasma 
concentrations of drugs that are substrates of CYP2C19 (e.g., omeprazole) but 
this only requires attention if very high doses are used such as in Zollinger-
Ellison syndrome.
3.5 
Study 
Flowchart 
A study flow chart is highly recommended.  It should display all clinical and laboratory 
measurements and the time periods (e.g., hours, days, and/or weeks) at which data are 
to be collected. 
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3.6 
Study 
Procedure
s 
This section is a detailed explanation of the experimental design.  The use of 
subheadings, lists, tables, or outlines are recommended.  Describe the initial screening 
period(s), baseline period(s), treatments to be compared, study configuration (e.g., 
parallel, crossover, etc.), duration of the treatment period(s), control group(s), follow-up 
procedures, and length of time specified for washout intervals and safety follow-up. 
This section should also include subject withdrawal criteria (e.g, terminating 
investigational product treatment/trial treatment) and procedures specifying: 
a)
When and not to withdraw subjects from the trial/investigational product 
treatment; 
b)
The type and timing of the data to be collected for withdrawn subjects; 
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c)
Whether and how subjects are to be replaced; 
d)
The follow-up for subjects withdrawn from investigational product 
treatment/trial treatment. 
The study will be submitted for IRB approval by the Mount Sinai Institutional 
Review Board and registered with the clinical trials office. A determination will 
be made regarding eligibility of this study for an Investigational New Drug (IND) 
exemption.  
The following parameters will be measured: 
Adenoma Size:  All patients will have baseline imaging (CT or MRI) within 6 
months to start of treatment and then will have repeat imaging with CT 
abdomen without contrast at 6 months to determine the effect of elagolix 
treatment on adrenal adenoma size and imaging characteristics. The images will 
be reviewed by a dedicated adrenal radiologist for consistency. 
Clinical Exam and parameters:  At baseline, one month, 3 months and 6 months 
patient will have full physical exam include measurement of vital signs.  Body 
weight and waist circumference will be measured.  Weight will be measured 
without overcoat and shoes and with only light clothing.  Waist circumference 
measurements will be obtained to the nearest 0.5 cm following removal of 
clothing from the waistline. Waist circumference will be measured in 
centimeters (cm) in the horizontal plane midway between the lowest ribs and 
the iliac crest (16). 
     In addition at baseline, three month and 6 month study visits patients will 
have a measurement of proximal muscle strength utilizing the sit to stand test.
The test evaluates the ability of patients to go from standing to sitting in a chair 
and then getting up again with/without the use of their arms or other aids.  
Patients seated in a chair will be asked to fold their arms across their chests and 
to stand up from the seated position once.  If they are able to successfully rise 
from the chair, they will be asked to sit down again and then stand up and sit 
down, a total of 5 times as quickly as possible.  Study staff will use a stopwatch 
to measure the total time it takes for the patient to stand up and sit down five 
times.  Start time is in the seated position and stop time is in the final standing 
position.  The total time of the test is measured.  
Cortisol Secretion and Metabolic Parameters:  At the baseline, 3 and 6 month 
study visits, patients will undergo a history and physical examination, including 
measurement of weight, blood pressure and waist circumference.   Fasting 8AM 
laboratory testing will be obtained, including a comprehensive metabolic panel, 
cortisol, ACTH, DHEAS, hemoglobin A1c, preserved glucose and insulin levels, 2 
hour oral glucose tolerance test, lipid profile, LH and estradiol. Fasting glucose 
and insulin level will be used to calculate HOMA-IR (Homeostatic Model 
Assessment for Insulin Resistance).  Results of oral glucose tolerance testing 
and C-peptide values to calculate a Matsuda index, oral disposition index, 
and HOMA IR (all measures of insulin resistance). Dexamethasone 
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suppression test will be performed at baseline and completion of the study. In 
addition, 24 hour urine free cortisol measurements will be done at time 0, 3 and 
6 months.   
Bone turnover markers and vertebral fracture rate:  At the baseline and 6 
months determination of serum c-telopeptide (CTX), a marker of osteoclastic 
activity and osteocalcin (a marker of osteoblastic activity) will be determined.  
Previous studies have demonstrated a suppressive effect of high cortisol on 
osteocalcin with return to normal levels after treatment (17). Fragility, or low 
traumatic fractures, which are fractures associated with either minimal or no 
discernible trauma, is a common complication of endogenous Cushing’s 
syndrome (1). Mild hypercortisolism has also been shown to increase vertebral 
fracture rates and a recent study demonstrated that surgical adrenalectomy for 
SH due to adrenal adenomas reduces vertebral fractures.  Interestingly, bone 
density measurements may underestimate the deleterious effects of 
glucocorticoids on bone quality (9).   Accordingly, baseline and 6 month 
vertebral fractures rates will be assessed by lateral X-rays of thoracic and 
lumbar spine. 
Study subjects are allowed to take Calcium and Vitamin D. 
Mood and Quality of Life Measures:   Patients will also complete several 
validated surveys at baseline and 6 months’ treatment, including Cushing QOL 
(18), Nottingham Health Profile (19), Beck’s Depression Scale (20), State Trait 
Anxiety Inventory (STAI) (21) and a visual analogue scale assessing hunger, 
fullness, and satiety (22). The surveys will be scored based on validated scoring 
system.
Safety Monitoring and Subject Withdrawal Criteria: Patients will be assessed at 
baseline, one month, three months and six months including history, physical, 
and laboratory testing (comprehensive metabolic panel and complete blood 
count with differential).  Study drug will be discontinued for any adverse 
reactions including nausea, vomiting, and/or diarrhea, a single episode 
occurring within 6-8 hours after administration of Elagolix.  Drug will also be 
discontinued for elevations greater than 3-4x normal in liver function tests, any 
abnormalities in electrolytes (above or below normal range) or kidney function 
(elevation of BUN and/or creatinine above normal range) and any abnormalities 
in hematologic parameters. 
Procedures for Reporting a Serious Adverse Event (SAE):  Any SAE occurring 
from the time of signing of the informed consent form (ICF) and for at least 30 
days after the last dose of study drug must be reported within 24 hours to the 
designated safety contact and recorded on the SAE form.  The investigator will 
supply the sponsor and the IRB/IEC with any additional requested information.
Adverse Event Follow-up:  All adverse events will be followed until resolution, 
until deemed stable by the Principal Investigator, or until the patient is deemed 
by the Principal Investigator to be lost to follow-up.  
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3.7 
Statistical 
Analysis 
and 
Sample 
Size 
Justificatio
n 
The statistical methods proposed to be used for the analysis of data should be clearly 
outlined, including reasons for the sample size selected, power of the study, level of 
significance to be sued, procedures for accounting for any missing or spurious data, etc.  
For projects involving qualitative approaches, specify in sufficient detail how the data 
will be analyzed. 
State who will be responsible for analyzing the study data (e.g., investigator, contract 
CRO, etc.). 
Investigator will be responsible for analyzing the study data. The significance of 
the effect of elagolix treatment on different outcome measures will be assessed 
with the Wilcoxon matched-pairs signed rank test to generate a two-tailed p-
value. Calculations will be performed with Prism 6 (Graphpad Software, Inc.). 
Sample Size Justification: No hypothesis testing, pilot study. 
3.8 
Specific 
Drug 
Supply 
Requirem
ents 
The investigator is responsible for keeping accurate records of the clinical supplies, the 
amount dispensed to and returned by the subjects, and the disposition at the end of the 
study.   
Clinical supplies must be received by a designated person at the study site, handled and 
stored safely and properly, and kept in a secured location to which only the investigator 
and designated assistants have access.  Clinical supplies are dispensed in accordance 
with the protocol.   
The investigator will be responsible for the destruction of the supplies at the study 
center pursuant to the ICH/GCP Guidelines, local regulations, and the investigator’s 
institutional policies.   
Elagolix 200 mg BID has an acceptable safety profile and results in rapid 
suppression of LH (23).  We selected this dose because it has been deemed to 
be safe and we are aiming for maximal efficacy.  Once screened and with 
informed consent, patients will be administered elagolix 200 mg orally twice 
daily for a total of 6 months.
3.9 
Safety 
Reporting 
In addition to compliance with all FDA reporting requirements pursuant to 21 CFR 312, 
the Principal Investigator shall: 
a)
Report to AbbVie all serious adverse events (SAEs) experienced by a study 
subject receiving an AbbVie product within 24 hours of learning of the event 
regardless of the relationship of the event to the AbbVie product.  Principal 
Investigator shall make available to AbbVie promptly such records as may be 
necessary and pertinent to investigate any such event, if specifically requested 
by AbbVie, and, 
b)
Copy AbbVie on the submission to the FDA of events meeting the definition of 
IND safety reports at the time of submission to the Agency; and, 
c)
Notify AbbVie upon any subjects receiving an AbbVie Product whose pregnancy 
has resulted in a negative outcome or untoward event during the course of 
pregnancy or upon delivery. 
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’s contact for reporting serious adverse drug experiences, pregnancy experiences, and 
communications of FDA submissions of IND safety reports shall be 
PPDINDPharmacovigilance@abbvie.com
t Complaints:  In addition to compliance with all FDA requirements pursuant to 21 CFR 
211 and 21 CFR 820, Principal Investigator will report to AbbVie within 24 hours any 
suspected quality defect in an AbbVie Product or its AbbVie-provided packaging, 
labeling, or medical device component (collectively, “Product Complaint”).  Principal 
Investigator will report Product Complaints that involve an AbbVie Product, whether 
AbbVie has supplied the AbbVie Product used in the Study or not.  AbbVie’s contact for 
reporting Product Complaints shall be RD_PQC_QS@abbvie.com
ollection of non-serious adverse events may be added per product-specific requirements. 
The events to be collected and the timing of this reporting should be included in this 
section as required.> 
Patients will be evaluated and questioned to identify AEs during the study. 
Collection of AEs will start immediately following the signing of the informed 
consent forms. Illnesses present before the patient signs the consent are 
considered pre-existing conditions and are documented on the medical history. 
Adverse events that occur after the start of the study drug and up to and 
including 30 days after administration of the last dose of study drug will be 
considered treatment emergent adverse events. Any adverse events reported 
more than 30 days after the last dose of study drug will be considered post 
treatment AEs.  
Any AEs/SAEs occurring from the time of signing the ICF and for at least 30 days 
after the last dose of study drug will be reported within 24 hours to the 
designated safety contact and recorded on the SAE form. All patients with an 
SAE will be followed and the outcomes will be reported. All AEs will be followed 
until resolution or until deemed stable by the Principal Investigator or until the 
patient is deemed to be lost to follow-up.  
SAEs will be reported in accordance to FDA requirements and AbbVie will be 
informed on these cases.
3.10 
Reference
s 
All literature references cited in the protocol should be listed accordingly in the 
reference section. 
1.
Nieman LK, Biller BM, Findling JW, Newell-Price J, Savage MO, Stewart 
PM, et al. The diagnosis of Cushing's syndrome: an Endocrine Society 
Clinical Practice Guideline. The Journal of clinical endocrinology and 
metabolism. 2008;93(5):1526-40. 
2.
Di Dalmazi G, Vicennati V, Garelli S, Casadio E, Rinaldi E, Giampalma E, 
et al. Cardiovascular events and mortality in patients with adrenal 
incidentalomas that are either non-secreting or associated with 
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intermediate phenotype or subclinical Cushing's syndrome: a 15-year 
retrospective study. The lancet Diabetes & endocrinology. 
2014;2(5):396-405. 
3.
Androulakis, II, Kaltsas GA, Kollias GE, Markou AC, Gouli AK, Thomas DA, 
et al. Patients with apparently nonfunctioning adrenal incidentalomas 
may be at increased cardiovascular risk due to excessive cortisol 
secretion. The Journal of clinical endocrinology and metabolism. 
2014;99(8):2754-62. 
4.
Debono M, Bradburn M, Bull M, Harrison B, Ross RJ, Newell-Price J. 
Cortisol as a marker for increased mortality in patients with incidental 
adrenocortical adenomas. The Journal of clinical endocrinology and 
metabolism. 2014;99(12):4462-70. 
5.
Di Dalmazi G. Update on the risks of benign adrenocortical 
incidentalomas. Current opinion in endocrinology, diabetes, and 
obesity. 2017;24(3):193-9. 
6.
Morelli V, Eller-Vainicher C, Salcuni AS, Coletti F, Iorio L, Muscogiuri G, 
et al. Risk of new vertebral fractures in patients with adrenal 
incidentaloma with and without subclinical hypercortisolism: a 
multicenter longitudinal study. Journal of bone and mineral research: 
the official journal of the American Society for Bone and Mineral 
Research. 2011;26(8):1816-21. 
7.
Tauchmanova L, Pivonello R, De Martino MC, Rusciano A, De Leo M, 
 Ruosi C, et al. Effects of sex steroids on bone in women with subclinical 
or overt endogenous hypercortisolism. European journal of 
endocrinology. 2007;157(3):359-66. 
8.
Morelli V, Eller-Vainicher C, Salcuni AS, Coletti F, Iorio L, Muscogiuri G, 
et al. Risk of new vertebral fractures in patients with adrenal 
incidentaloma with and without subclinical hypercortisolism: a 
multicenter longitudinal study. Journal of bone and mineral research: 
the official journal of the American Society for Bone and Mineral 
Research. 2011;26(8):1816-21. 
9.
Salcuni AS, Morelli V, Eller Vainicher C, Palmieri S, Cairoli E, Spada A, et 
al. Adrenalectomy reduces the risk of vertebral fractures in patients 
with monolateral adrenal incidentalomas and subclinical 
hypercortisolism. European journal of endocrinology. 2016;174(3):261-
9. 
10. Teo AE, Garg S, Shaikh LH, Zhou J, Karet Frankl FE, Gurnell M, 
Happerfield L, Marker A, Bienz M, Azizan EA, Brown MJ (2015) 
Pregnancy, Primary Aldosteronism, and Adrenal CTNNB1 Mutations. 
The New England journal of medicine 373 (15):1429-1436.  
11. Kogekar N., Haines K., Kirschenbaum A., Yao S., Inabnet, W.B., and 
Levine, A.C.  Luteinizing hormone/human chorionic gonadotropin 
receptor, Gata-4 and Beta-catenin expression in human adrenal cortical 
neoplasia. 99th Annual Meeting of the Endocrine Society, Orlando, FL, 
April 2017.  
12. Belokovskaya, R., Yao, S., Kirschenbaum, A. and Levine, 
A.C.  Immunohistochemical Expression of Luteinizing Hormone/Human 
Chorionic Gonadotropin Receptor (LH/hCG Receptor) in Adrenal 
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Adenomas of Postmenopausal Women. 101st Annual Meeting of the 
Endocrine Society, New Orleans, LA, March 2019. 
13. Lasley, Bill, et al. "Identification of immunoreactive luteinizing hormone 
receptors in the adrenal cortex of the female rhesus macaque." 
Reproductive Sciences 23.4 (2016): 524-530. 
14. Saxena, Aditi R., and Ellen W. Seely. "Luteinizing hormone correlates 
with adrenal function in postmenopausal women." Menopause (New 
York, NY) 19.11 (2012): 1280. 
15. Doroszko, Milena, et al. "GnRH antagonist treatment of malignant 
adrenocortical tumors." Endocrine-related cancer26.1 (2019): 103-117. 
16. Ma WY, Yang CY, Shih SR, Hsieh HJ, Hung CS, Chiu FC, et al. 
Measurement of Waist Circumference: midabdominal or iliac crest? 
Diabetes care. 2013;36(6):1660-6. 
17. Guo W, Li F, Zhu C, Wang B, Wang K, Dai C. Effect of hypercortisolism on 
bone mineral density and bone metabolism: A potential protective 
effect of adrenocorticotropic hormone in patients with Cushing’s 
disease. J Int Med Res. 2018;46(1): 492–503. 
18. Webb SM, Badia X, Barahona MJ, Colao A, Strasburger CJ, Tabarin A, et 
al. Evaluation of health-related quality of life in patients with Cushing's 
syndrome with a new questionnaire. European journal of 
endocrinology. 2008;158(5):623-30. 
19. Wiklund I. The Nottingham Health Profile--a measure of health-related 
quality of life. Scandinavian journal of primary health care Supplement. 
1990;1:15-8. 
20. Whisman MA, Perez JE, Ramel W. Factor structure of the Beck 
Depression Inventory-Second Edition (BDI-II) in a student sample. 
Journal of clinical psychology. 2000;56(4):545-51. 
21. Tluczek A, Henriques JB, Brown RL. Support for the reliability and 
validity of a six-item state anxiety scale derived from the State-Trait 
Anxiety Inventory. Journal of nursing measurement. 2009;17(1):19-28. 
22. Raben A, Tagliabue A, Astrup A. The reproducibility of subjective 
appetite scores. The British journal of nutrition. 1995;73(4):517-30. 
23. Struthers, R. Scott, et al. Suppression of gonadotropins and estradiol in 
premenopausal women by oral administration of the nonpeptide 
gonadotropin-releasing hormone antagonist elagolix. The Journal of 
Clinical Endocrinology & Metabolism 94.2 (2009): 545-551. 
24. Feelders, RA, Newell-Price J, Pivonello R, Nieman LK, Hofland LJ,and 
LaCroix, A. Advances in the medical treatment of Cushing’s syndrome. 
Lancet Diabetes Endocrinology  2019 Apr;7(4): (2019): 300-312.
25.  Belokovskaya, R, Ravikumar A, Arumugam D, Izadmehr S, Goddard GM, 
Geer EB, and Levine AC.  Mifepristone treatment for mild autonomous 
cortisol secretion due to adrenal adenomas: a pilot study.  Endocrine 
Practice (Accepted for Publication April 5, 2019) 
26. Cynthia A. Stuenkel, Susan R. Davis, Anne Gompel, Mary Ann Lumsden, 
M. Hassan Murad, JoAnn V. Pinkerton, Richard J. Santen, Treatment of 
Symptoms of the Menopause: An Endocrine Society Clinical Practice 
Guideline, The Journal of Clinical Endocrinology & Metabolism, Volume 
100, Issue 11, 1 November 2015, Pages 3975–4011.
00121661.0

ICF_001.pdf: 
An Oral GnRH Antagonist to Treat Mild Autonomous Cortisol Excess (MACE) Due to 
Adrenal Adenomas in Postmenopausal Women
PI: Dr. Alice C. Levine
NCT05038878
Document Date: March 2023


___________________________ 
STUDY INFORMATION: 
Study Title:  An oral GnRH antagonist to treat mild autonomous cortisol excess (MACE) due to 
adrenal adenomas in postmenopausal women 
Study site(s): The Mount Sinai Hospital 
Lead Researcher (Principal Investigator): Alice C Levine 
Physical Address: Endocrine Associates, 5 E 98th Street, 3rd Floor New York, NY 10029 
Mailing Address: One Gustave L Levy Place Box 1055 New York, NY 10029 
Phone: 212-241-3422 
____________________________ 
SUMMARY OF THIS RESEARCH STUDY: 
This document explains a research study you might be interested in joining.  Participation in the 
study is voluntary. You can agree to join or not. Your decision will not limit your ability to receive 
care at Mount Sinai. You should only agree to take part if you understand the study and if all of 
your questions about the research study are answered. If you do join the study, the research 
team must share any new information with you that may change your mind about taking part.  
The purpose of this research study is to determine if treatment with the study drug Elagolix will 
improve body weight, waist size, muscle strength, secretion of cortisol (a stress hormone), blood 
sugar, cholesterol (a fat-like substance found in your blood), and bone quality as well as mood 
and quality of life in a female patient with mild elevation of cortisol due to overproduction of the 
hormone by the adrenal gland (an endocrine organ). Many people with adrenal nodules, or non-
cancerous growths in the adrenal glands, have mildly elevated cortisol levels. Cortisol is a 
hormone normally made by the adrenal glands. It is increasingly being recognized that even 
mild elevations in cortisol levels can negatively impact blood glucose levels, serum cholesterol 
levels, and weight. This can lead to an increase in risk for heart disease. Our team is trying to 
determine if the medication Elagolix might be an effective treatment for post-menopausal 
females with mild elevation of cortisol. Elagolix is a medication used to treat a medical condition 
called endometriosis, a condition in which the uterine's inner lining tissue is found outside the 
uterus. The growth of this uterine lining is controlled by reproduction hormones and can be 
painful but can be effectively treated with Elagolix which limits the release of these hormones. 
Growth of adrenal adenomas is also thought to be driven by such sex hormones. Therefore, by 
decreasing production of these hormones, we hope to treat hypercortisolism caused by adrenal 
adenomas. 
If you choose to take part, you will be asked to take Elagolix for 6 months. You will attend 4 
visits: before starting Elagolix, and 1 month, 3 months, and 6 months after starting Elagolix. The 
procedures involved during visits will include a full physical exam, including measurement of 
vital signs, body weight, and waist circumference (the distance around your waist using a 
measuring tape), a test of muscle strength called a “sit to stand” test, urine collection, and blood 
collection via venipuncture. All blood and urine specimens will be discarded once the lab values 
have resulted. Additionally, at baseline and 6 month study visits, you will have X-rays of the 


spine to determine if you have spine fractures and a special X-ray called a DEXA scan to 
assess your amount of body fat. You will have had a baseline bone density study done and 
reviewed as part of standard of care for post-menopausal women.  
This drug, Elagolix, will be provided to you by the drug manufacturer, AbbVie. You will not have 
to pay for the drug or the study visits. Taking part in this research study may lead to added costs 
to you in terms of travel to the visits. There will be no monetary compensation for your time.  
If you choose to take part, the main risks to you are cost/time of travel, and low risk of potential 
adverse effects of the Elagolix as outlined in detail below.  
You will not benefit directly from taking part in this research. However, possible benefits may be 
improvement in blood glucose levels, blood pressure and cholesterol, weight loss, decrease in 
waist circumference, improvement in bone quality, improvement in muscle strength, and/or 
improvement in quality of life.  
If you are interested in learning more about this study, please continue to read below. 
____________________________ 
STUDY PARTICIPATION: 
You may qualify to take part in this research study because you are a post-menopausal female 
and have non-cancerous appearing growth in your adrenal gland with mild elevations in your 
serum cortisol (stress hormone) levels, salivary cortisol levels, and/or urinary cortisol/cortisone 
levels.  
Your participation in this research study is expected to last about 6 months. 
There are 12 people expected to take part in this research study at the Mount Sinai Hospital. 
Funds for conducting this research are provided by a research grant provided by Abbvie 
Pharmaceuticals, the manufacturer of the drug.  
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by 
U.S. Law. This website will not include information that can identify you. At most, the website 
will include a summary of the results. You can search this website at any time. 
____________________________ 
DESCRIPTION OF WHAT’S INVOLVED: 
If you agree to participate in this research study, the following information describes what may 
be involved.  
Your medical chart will be reviewed including: results of your baseline bone density and 
abdominal CT scan or MRI showing an incidentally noted, benign appearing adrenal nodule as 
well as results of a 24- hour urine free cortisol/cortisone test, a test that determines levels of this 
hormone in your urine collected over 1 day, 2 midnight salivary cortisol tests, a test that 
measures the cortisol in your saliva, a dexamethasone suppression test, a blood test that looks 
at cortisol levels in the blood 12 hours after taking an oral medication, dexamethasone, blood 


levels of ACTH, a hormone produced by the brain that tells the adrenal glands to make cortisol, 
DHEAs, another hormone made by the adrenal glands, vitamin D levels, plasma glucose, a 
blood test to check sugar levels in your blood at the moment the blood is drawn, and HgA1C, a 
blood test to see what your blood sugar levels have been on average over the last 3 months. If 
previously completed, an oral glucose tolerance test will also be reviewed, during which the 
participants blood is drawn to measure preserved glucose levels both prior to and 2 hours after 
drinking a glucose solution. These tests are part of the standard work-up of an incidentally noted 
adrenal nodule, and will be reviewed for the study.  
You will be scheduled for an initial study visit to which you should arrive not having eaten or 
drunk anything, except water, in the past 8 hours. This and all following visits will take place in 
the FPA Endocrine clinic (5 E 98th St 3rd Floor, New York, NY 10029) or the IMA Endocrine 
clinic at Mount Sinai (17 E 102nd St, New York, NY 10029). During this visit you will have blood 
drawn for the following tests: serum comprehensive metabolic panel (liver function, kidney 
function and electrolytes), preserved glucose (blood sugar), insulin level, HbA1c (your average 
blood sugars over about 3 months), blood cholesterol levels, complete blood count (a test of 
your blood cell levels), cortisol (a stress hormone), ACTH (a hormone that triggers production of 
cortisol, DHEAS (a test of adrenal gland function, LH (a sex hormone), estradiol (a sex 
hormone), 25OH vitamin D (vitamin D level), CTX (a marker of bone breakdown), and 
osteocalcin (a marker of bone formation). A 2 hour oral glucose tolerance test will be performed 
as outlined above. A 24 hour urine free cortisol/cortisone test will be performed as outlined 
above. Approximately 2 teaspoons of blood will be drawn via routine blood drawing practices by 
a trained member of the research team. These laboratory studies are part of the standard care 
of a patient being treated for hypercortisolism. Your height, weight, waist circumference and 
blood pressure will be measured by a member of the study team. You will be asked to complete 
a test to measure appetite and 3 surveys to assess your quality of life as well as 3 additional 
questionnaires to assess mood and measure your appetite. This visit will last for about 60 
minutes. At the initial study visit you will receive a one-month supply of the study drug, Elagolix. 
Elagolix is taken twice daily at a dose of 200mg. The dose will not be adjusted. You will take the 
medication for the full 6 months of your study participation. All participants will receive the study 
medication. Additionally, at baseline you will have X-rays of the spine to determine if you have 
spine fractures and a special X-ray called a DEXA scan to assess your amount of body fat. 
You will be scheduled for follow-up study visits with a member of the study team at 1 month, 3 
months, and 6 months after initiation of Elagolix. At your 1 month visit, you will have blood 
drawn for a complete blood count and a serum comprehensive metabolic panel, and your blood 
pressure and weight will be checked. Approximately 1 teaspoon of blood will be drawn at each 
visit via routine blood drawing practices by a trained member of the research team. These 
laboratory studies are part of the standard care of a patient being treated for hypercortisolism. 
Any change in symptoms or any medication side effects will be recorded. You will receive a 
prescription for a one-month supply of the study drug elagolix. This visit will last approximately 
15-30 minutes.
At the 3 month visit, you will arrive not having eaten or drunk anything for the past 8 hours. You 
will be have blood drawn for the following tests: comprehensive metabolic panel, preserved 
glucose, insulin level, HbA1c, blood cholesterol levels, complete blood count, cortisol, ACTH, 
DHEAS. A 2 hour oral glucose tolerance test will be performed as outlined above. A 24 hour 
urine free cortisol/cortisone test will be performed as outlined above. Approximately 2 teaspoons 
of blood will be drawn via routine blood drawing practices by a trained member of the research 
team. Your height, weight, waist circumference (the distance around your waist using a 


measuring tape) and blood pressure will be measured by a member of the study team. This visit 
will last approximately 15-30 minutes.  
 
After taking the study medication for 6 months you will be scheduled for a final study visit with a 
member of the study team to which you will arrive not having eaten or drunk anything for the 
past 8 hours. You will have blood drawn for the following tests: comprehensive metabolic panel, 
preserved glucose, insulin level, HbA1c, blood cholesterol levels, complete blood count, cortisol, 
ACTH, DHEAS, LH (a sex hormone), estradiol (a sex hormone), CTX (a marker of bone 
breakdown), and osteocalcin (a marker of bone formation). A 2 hour oral glucose tolerance test 
will be performed as outlined above. A 24 hour urine free cortisol/cortisone test will be 
performed as outlined above. Approximately 2 teaspoons of blood will be drawn via routine 
blood drawing practices by a trained member of the research team. Your height, weight, waist 
circumference (the distance around your waist using a measuring tape) and blood pressure will 
be measured by a member of the study team. You will be asked to complete the same test to 
measure appetite and 3 surveys to assess your quality of life that you completed at the initial 
study visit. This visit will last 60-90 minutes. Additionally, 6 month study visits, you will have X-
rays of the spine to determine if you have any new spine fractures and a special X-ray called a 
DEXA scan to assess your amount of body fat.  
 
After this visit you will stop taking Elagolix and your participation in the study will be complete. 
All blood samples will be discarded according to the routine procedures of the Mount Sinai 
laboratory once the indicated tests have been performed.  
 
Elagolix interacts with a number of other medications and foods. Patients taking one of these 
medications on a daily or regular basis should not take Elagolix. You should let your doctor 
know what medications you are taking. While you are taking Elagolix, you should advise your 
physicians that you are taking this medication before starting any new medication. If you have 
questions regarding this information now or during your study participation you may ask a 
member of the study team.  
 
Clinically relevant research results, including individual research results, will be disclosed to 
participants, on an ongoing basis. Please note that only the results of FDA or New York State 
approved tests that are performed in a CLIA-certified lab can be shared with participants. 
 
Because this research study involves the use of Elagolix, a note must be included in your 
electronic medical record that you are taking part in the research. This way, anyone involved in 
your medical care will know that you are a study participant, and they can work to avoid any 
problems or negative outcomes that could arise if they do not know. 
 
____________________________ 
Future Contact: 
The researchers may wish to use your personal contact information to contact you in the future. 
Do you give the researchers permission to contact you in the future to request the collection of   
additional information about you, discuss how your private information, study data and/or 
samples might be used, or discuss possible participation in another research study? 
  
Please initial your choice: Yes_________ No__________ 
  


If “Yes”, please indicate your preferred method of contact: (initial all that apply) 
        
[  ] Email         [  ] Phone       [  ] Letter          [  ] Text 
 
____________________________ 
USE OF YOUR DATA AND/OR SAMPLES: 
 
The research team will never use or share your personal information (such as, name, address, 
date of birth, social security number), study data and/or samples (blood, tissue, urine, saliva, or 
any other body matter) that are collected as part of this study for future research, even if your 
identity is removed. Your data and/or samples will only be used to complete this study and then 
they will be destroyed. 
____________________________ 
YOUR RESPONSIBILITIES IF YOU TAKE PART IN THIS RESEARCH: 
If you decide to take part in this research study you will be responsible for the following things:  
1. Attending study visits 
2. Taking prescribed dose of Elagolix 
3. Avoiding medications that interact with Elagolix 
4. Calling the study team to report the side effects listed above 
____________________________ 
COSTS OR PAYMENTS THAT MAY RESULT FROM PARTICIPATION: 
You will not be paid for participating in this research study. Being in this study will not cost you 
anything extra. Researchers will not pay you for your travel or the time it will take for you to be in 
the study.  
____________________________ 
POSSIBLE BENEFITS: 
This study is not designed to benefit you personally. However, possible future benefits to others 
include improvement in blood glucose levels, blood pressure and cholesterol, weight loss, 
decrease in waist circumference, improvement in bone quality, improvement in muscle strength, 
and/or improvement in quality of life. The investigational drug provided at no cost during the 
study may not be available at the end of the research or may no longer be provided at no cost to 
you if the drug becomes available for marketing.  
____________________________ 
POSSIBLE RISKS AND DISCOMFORTS: 
The study requires venous blood drawing, a procedure that involves application of a tourniquet 
(a device which applies pressure to a limb) and blood removal with a needle. The risks of a 
blood draw include pain, bruising, and the slight possibility of infection at the place where the 
needle goes in. Some people feel dizzy or may faint during or after a blood draw.  
 
Possible risks include medication side effects. The most common side effects seen with prior 
use of the drug are hot flashes, night sweats, headache, nausea, insomnia, loss of menses, 
anxiety, joint pains, depression, mood changes, and a decrease in bone density. These effects 
are a result of low estradiol, or female sex hormone levels. However, we expect you will not 
experience most of these effects as you are post-menopausal and thus already have low 


estradiol. Other warnings/precautions include suicidal ideation, suicidal behavior, worsening of 
mood disorders, and liver enzyme elevations which can resolve with discontinuation of the drug. 
You will be monitored for side effects and adverse reactions of the medication and will receive 
laboratory screening for any metabolic abnormalities.  
 
This research study includes exposure to radiation from x-rays or gamma rays. This radiation 
exposure is for research purposes only and is in addition to any radiation needed for your 
medical care. X-rays and gamma rays from natural or medical sources can damage the genetic 
material (DNA) in your cells. At low radiation exposures, the body is usually able to repair the 
damage. Radiation risk is believed to be related to the total lifetime exposure. You should think 
about your own history of radiation exposure from tests (like x-rays or CT scans) in deciding 
about the radiation in this study. If you have questions about the total amount of radiation 
exposure you will be receiving, you should ask your doctor.  
 
The estimated radiation exposure that you will get for this research study will be 2 mSv (an mSv 
is the scientific unit of measurement for whole body radiation dose also known as the "effective 
dose"). This is less than the 6.2 mSv that the average person in the United States gets each 
year from both natural sources like the sun, outer space, air, food, and soil, as well as from 
medical procedures. The risk from the radiation exposure in this research study is very small. 
 
As with any investigational study, there is a risk of loss of private information. This risk always 
exists, but there are procedures in place to minimize the risk..  
 
In addition to these risks, this research study may hurt you in ways that are not known. The 
unknown risks could be minor or major (death). 
____________________________ 
OTHER OPTIONS TO CONSIDER: 
You may decide not to take part in this research study without any penalty.  The choice is totally 
up to you. Instead of being in this research study, your choices may include:  
 
 
• 
Treatment of symptoms such as high levels of glucose or sugar in the blood, high blood 
pressure and high cholesterol individually.  
• 
Evaluation for surgical resection of the adrenal gland containing the adrenal nodule  
• 
Watchful waiting 
The important risks and possible benefits of these alternatives are listed below:  
• 
Difficulty treating hyperglycemia, high blood pressure and high cholesterol due to 
untreated mild elevations in cortisol. This may mean the several medications are 
required for the treatment of these conditions. Benefits of participating in the study may 
include control of these conditions with fewer medication side effects.  
• 
Surgical procedures always involve risks including infection, bleeding and death. 
Benefits include surgical cure of mild hypercortisolism and improvement in resulting 
metabolic derangements without the use of medications.  
____________________________ 
IN CASE OF INJURY DURING THIS RESEARCH STUDY: 


If you are injured or made sick from taking part in this research study, medical care will be 
provided. Generally, this care will be billed to you or your insurance in the ordinary manner and 
you will be responsible for all treatment costs not covered by your insurance, including 
deductibles, co-payments and coinsurance.  This does not prevent you from seeking payment 
for injury related to malpractice or negligence. Contact the investigator for more information. 
 
If you are injured or made sick from taking part in this study, you will get medical care. The 
group funding this research study will pay you for any reasonable and necessary medical 
expenses to diagnose and treat research-related injury or illness. This does not prevent you 
from seeking payment for injury related to malpractice or negligence. You can contact the Lead 
Researcher for more information. 
 
____________________________ 
ENDING PARTICIPATION IN THE RESEARCH STUDY: 
 
You may stop taking part in this study at any time.  No matter what you choose, your care and 
benefits through Mount Sinai will not be negatively impacted. 
  
If you decide to stop being in the study, please contact the Lead Researcher or the research 
staff.  The study medication Elagolix will be stopped and you will be referred to your Primary care 
doctor or endocrinologist for further evaluation for the need for treatment of any elevations in 
blood glucose, high blood pressure, high cholesterol or overweight. 
 
You may also withdraw your permission for the researchers to use and share any of your 
protected information for research, but you must do so in writing to the Lead Researcher at the 
address on the first page. Even if you withdraw your permission, the Lead Researcher may still 
use the information that was already collected if that information is necessary to complete the 
research study. Your health information may still be used or shared after you withdraw your 
authorization if you have an adverse event (a bad effect) from taking part in the research study. 
 
If you decide to stop being in the research study, the following may occur: return of previous 
elevations in blood glucose requiring treatments, elevations in blood pressure requiring 
antihypertensive medications, elevations in cholesterol requiring medications, weight gain.  
 
If you stop being in the research study, the research team may not remove information they have 
already placed in the study database, and may continue to use that data as part of this study. The 
research team may ask you whether they can continue to collect information from your medical 
record.   
 
If you decide you don’t want your data and/or samples to be used for research anymore, you can 
contact the researcher and ask to have your data and/or samples withdrawn or labeled so that 
they will not to be used in additional projects or shared. If your data and/or samples have already 
been shared with researchers, those researchers will be asked to stop using them. However, if 
any data and/or samples have already been shared without your identity or a linking code, it won’t 
be possible to retrieve them. Data and/or samples that have already been used will not be affected 
by your decision. If your data and/or samples have already been deposited in an external 
repository, the study team will request that your data and/or samples be removed. 
  


Withdrawal without your consent: The Lead Researcher, the funder or Mount Sinai may stop your 
involvement in this research study at any time without your consent. This may be because the 
research study is being stopped, the instructions of the research team have not been followed, 
the Lead Researcher believes it is in your best interest, or for any other reason. If data and/or 
samples have been stored as part of the research study, they too can be destroyed without your 
consent.   
____________________________ 
CONTACT INFORMATION: 
If you have any questions, concerns or complaints at any time about this research, or you think 
the research has harmed you, please contact the office of the research team and/or the Lead 
Researcher at phone number.  
 
If there is an emergency, please call 212-241-3422. or call 911 or go to the emergency room. 
Let the emergency room staff know you are in a research study so they can contact the Lead 
Researcher if needed. 
 
___________________________ 
DISCLOSURE OF FINANCIAL INTERESTS: 
Researchers sometimes get paid for consulting or doing work for companies that produce drugs, 
biologics or medical devices. If you have questions regarding industry relationships, you are 
encouraged to talk to the Lead Researcher or visit our website at http://icahn.mssm.edu/ where 
Mount Sinai publicly discloses the industry relationships of our faculty.    
 
The company (Abbvie, Inc.) sponsoring this research study manufactures the drug being tested 
and so has a financial interest that could be affected by the outcome of this research study. 
 
____________________________ 
MAINTAINING CONFIDENTIALITY – HIPAA AUTHORIZATION: 
As part of this study, some of your private and/or protected health information will be obtained, 
used, and shared with your permission. There is a Federal Health Insurance Portability and 
Accountability Act (HIPAA) that makes sure this is done correctly and safely. 
  
What is protected health information (PHI)? 
PHI is the combination of two things: 
1.  
PHI contains information that identifies you. It will be used to contact you and link 
you to your health information, like name, date of birth, medical record number, and 
address.   
2.  
PHI also contains health information, including information about your mental and 
physical health from your visits to doctors or hospitals, or from study visits. 
  
Every time you visit a hospital or your doctor, PHI is created and recorded in your medical record 
by your healthcare providers. In the same way, the PHI created as part of this study will be linked 
to who you are and your medical information. 
 
What PHI is collected and used in this research study, and might also be shared with others? 


As part of this research project, the researchers will collect your name, address, telephone/fax 
numbers, dates directly related to the individual medical records number, health plan numbers  
The researchers will also get information from your medical record at the Mount Sinai Hospital 
and if applicable your private doctor. 
During the study the researchers will gather information by:  
• 
Reviewing and/or taking your medical history (includes current and past medications or 
therapies, illnesses, conditions or symptoms, family medical history, allergies, etc.) 
• 
Doing a physical examination that generally also includes blood pressure reading, heart 
rate, breathing rate, and temperature. 
• 
Completing the tests, procedures, questionnaires and interviews explained in the 
description section of this consent. 
 
Why is your PHI being used? 
Researchers need the information that identifies you so they can contact you during the study. 
They need your health information and the results of any tests and procedures being collected as 
part of this study to answer the questions posed in the study. The purpose of the study is 
discussed earlier in this consent form. Before researchers analyze the data, they remove any 
information that would let others know who you are or that you took part in the study. If researchers 
publish or present study results at scientific meetings, lectures, or other events, their 
presentations would not include any information that would let others know who you are, unless 
you give separate permission to do so. 
  
The Lead Researcher may also use and share the results of these tests and procedures with 
other healthcare providers at Mount Sinai who are involved in your care or treatment. The 
research team and other authorized members of The Mount Sinai Health System (“Mount Sinai”) 
workforce may use and share your information to ensure that the research meets legal, 
institutional or accreditation requirements. For example: 
• 
The Mount Sinai Program for the Protection of Human Subjects is responsible for 
overseeing research on human participants and may need to see your information. 
• 
If you receive any payments for taking part in this study, the Mount Sinai Finance 
Department may need your name, address, social security number, payment 
amount, and related information for tax reporting purposes.  
• 
If the research team uncovers abuse, neglect, or reportable diseases, this 
information may be disclosed to appropriate authorities. 
  
Who, outside Mount Sinai, might receive your PHI? 
As part of the study, the Lead Researcher, research team and others in the Mount Sinai workforce 
may disclose your PHI, including the results of the research study tests and procedures, to the 
following people or organizations: (It is possible that there may be changes to the list during this 
research study; you may request an up-to-date list at any time by contacting the Lead 
Researcher.) 
• 
The United States Department of Health and Human Services (DHHS) and the Office of 
Human Research Protection (OHRP) (the government organization that is responsible for 
protecting human research participants). 
• 
Outside laboratory who will be performing laboratory analysis for all the research centers 
involved in this project: Quest diagnostics and ACL Laboratories 


• 
The commercial sponsor and/or their representative (who will use the results for 
submissions to the Food and Drug Administration (the government organization that 
approves drugs or devices for medical use): Abbvie  
• 
The sponsoring government agency and/or their representatives who need to confirm the 
accuracy of the results submitted to the government or the use of government funds: FDA 
• 
-Contract Research Organization (whose job is to help organizations fulfill their 
responsibilities in the research and development process): IRB 
• 
A Data Safety Monitoring Board or other committee that will monitor the study on an 
ongoing basis for safety. 
• 
The United States Food and Drug Administration. 
• 
The United States Department of Health and Human Services and the Office of Human 
Research Protection. 
In all disclosures outside of Mount Sinai, you will not be identified by name, social security number, 
address, telephone number, or any other direct personal identifier unless disclosure of the direct 
identifier is required by law. Some records and information disclosed may be identified with a 
unique code number. The Lead Researcher will ensure that the key to the code will be kept in a 
locked file, or will be securely stored electronically. The code will not be used to link the 
information back to you without your permission, unless the law requires it, or rarely if the 
Institutional Review Board (IRB) allows it after determining that there would be minimal risk to 
your privacy. It is possible that a sponsor or their representatives, a data coordinating office, a 
contract research organization, may come to inspect your records. Even if those records are 
identifiable when inspected, the information leaving the institution will be stripped of direct 
identifiers.  Additionally, when applicable, the monitors, auditors, the IRB, OHRP, as well as the 
Food and Drug Administration (FDA) will be granted direct access to your medical records for 
verification of the research procedures and data. OHRP and FDA are authorized to remove 
information with identifiers if necessary to complete their task. By signing this document, you are 
authorizing this access. The results of this research may be published. However, your name and 
other identifying information will be kept confidential. 
 
For how long will Mount Sinai be able to use or disclose your PHI? Your authorization for use of 
your PHI for this specific study does not expire. 
 
Will you be able to access your records? 
During your participation in this study, you will have access to your medical record and any study 
information that is part of that record. The research team is not required to release research 
information to you that is not part of your medical record. 
 
Do you need to give the researchers permission to obtain, use or share your PHI? 
NO! If you decide not to let the research team obtain, use or share your PHI, you should not sign 
this form, and you will not be allowed to volunteer in the research study. If you do not sign, it will 
not affect your treatment, payment, or enrollment in any health plans or affect your eligibility for 
benefits. 
  
Can you change your mind? 
If you decide to stop being in the study, please contact the Lead Researcher or the research staff. 
The research team may ask you whether they can continue to collect information from your 
medical record. You will also have to decide if you wish to limit the continued use of the information 
collected during the study. Under US privacy laws you may also withdraw your permission for the 
researchers to use and share any of your protected information for research, but you must do so 
in writing to the Lead Researcher at the address on the first page. 


  
Even if you withdraw your permission, the Lead Researcher may still use the information that was 
already collected, but only to complete this research study. Your health information may still be 
used or shared after you withdraw your authorization if you have an adverse event (a bad effect) 
from taking part in the research study. 
 
If you have not already received it, you will also be given The Hospital’s Notice of Privacy 
Practices that contains more information about how The Hospital uses and discloses your PHI. 
  
It is important for you to understand that once information is disclosed to others outside Mount 
Sinai, the information may be re-disclosed and will no longer be covered by the federal privacy 
protection regulations. However, where possible, Mount Sinai has entered into agreements with 
those who will receive your information to continue to protect your confidentiality. 
  
If researchers are reviewing your medical records or asking questions about your medical history 
or conditions, it is possible that they may learn information related to your HIV status. If that is the 
case, the following information concerns you. If researchers are not reviewing your medical 
records or asking questions about your medical history or conditions, then you may ignore the 
following section. 
____________________________________________________________________________
_____ 
Notice Concerning HIV-Related Information 
If you are authorizing the release of HIV-related information, you should be aware that the recipient(s) 
is (are) prohibited from re-disclosing any HIV-related information without your authorization unless 
permitted to do so under federal or state law. You also have a right to request a list of people who may 
receive or use your HIV-related information without authorization. If you experience discrimination 
because of the release or disclosure of HIV-related information, you may contact the New York State 
Division of Human Rights at (888) 392-3644 or the New York City Commission on Human Rights at 
(212) 306-5070. These agencies are responsible for protecting your rights. 
________________________________________________________________________________
_____ 
 
Certificate of Confidentiality: To further protect your privacy, the researchers have obtained a 
Certificate of Confidentiality from the Department of Health and Human Services. This is intended 
to ensure that your identity as a participant in this research study will not have to be disclosed as 
a result from a subpoena, for the purpose of identifying you in any federal, state, or local civil, 
criminal, administrative, legislative, or other proceedings other than to the FDA or OHRP as 
identified above. 
  
The research staff will not share any of your personal information, study data and/or samples with 
anyone who is not a member of the research team, including any family members or friends, other 
than those identified above. However, you should know that if it is learned that you or someone 
else is threatened with serious harm, such as a child or an elderly person being abused, the 
research team may notify the appropriate authorities if necessary to protect you or others.  A 
Certificate of Confidentiality does not prevent you or a member of your family from voluntarily 
releasing information about yourself or your involvement in this research. This means that you 
and your family must also actively protect your own privacy. If an insurer or employer learns about 
your research participation, and you agree that they can have your research information, then the 
researchers may not use the Certificate of Confidentiality to keep this information from them. 
 


____________________________ 
How the Institutional Review Board (IRB) can help you: 
This research has been reviewed and approved by an Institutional Review Board (IRB). You 
may reach a representative of the Mount Sinai Program for Protection of Human Subjects at 
telephone number (212) 824-8200 during regular work hours (Monday-Friday, 9am-5pm, 
excluding holidays) for any of the reasons listed below. This office will direct your call to the right 
person within the Mount Sinai Health System: 
• 
Your questions, concerns, or complaints are not being answered by the research 
team. 
• 
You cannot reach the research team. 
• 
You are not comfortable talking to the research team. 
• 
You have questions about your rights as a research participant. 
• 
You want to get information or provide input about this research. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


ADULT PARTICIPANT: 
Your signature below documents your permission to take part in this research study and to the 
use and disclosure of your protected health information. A signed and dated copy will be given to 
you. 
  
  
_________________________      _________________________      __________
 
__________ 
Signature of Participant                   Printed Name of Participant            Date             
Time 
  
  
PERSON EXPLAINING STUDY AND OBTAINING CONSENT: 
  
  
_________________________      _________________________      __________
 
__________ 
Signature of Consent Delegate       Printed Name of Consent Delegate   Date             
Time 
  
  
WITNESS SECTION: 
  
My signature below documents that the information in the consent document and any other written 
information was accurately explained to, and apparently understood by, the participant, and that 
consent was freely given by the participant. 
  
  
  
_________________________      _________________________      __________
 
__________ 
Signature of Witness                       Printed Name of Witness                
Date             
Time