Clinical trial NCT04066647
Conditions: Dexamethasone Effect on miRNA Profile in Healthy Humans
Sponsor: Cedars-Sinai Medical Center
Start date: 2019-05-09; Completion date: 2019-07-24
Enrollment: 7 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The proposed study will test dexamethasone effect on miRNA profile in healthy humans. As our data indicate that miRNA levels change over time, the investigators will study the time course of miRNA response to 1 mg IV dexamethasone within 60 minutes after injection. Dexamethasone is used routinely in human subjects for the treatment of inflammatory conditions and as a diagnostic tool in the evaluation of excess cortisol secretion (Cushing's syndrome). For the latter, 1 mg dexamethasone is given orally at midnight. Oral formula absorption in the gut can range from 20 to 60 minutes due to the presence of food and other factors. IV administration will bypass this variability and ensure an accurate and reproducible time-course study. The investigators will compare miRNA expression before and after dexamethasone treatment. The investigators will follow miRNA expression dynamics over a 1-hour time course to identify peak expression levels and to correlate miRNA expression with circulating dexamethasone levels. Dexamethasone and miRNA levels will be checked at baseline just before injection and then at 15, 30, 45, and 60 minutes after injection. Dexamethasone level is taken to verify treatment and to correlate it with miRNA expression.

Detailed description:

Arms: arm 1: Single arm study in which all healthy controls will receive 1 mg of dexamethasone intravenous (IV) injection.
Interventions: intervention 1: Dexamethasone 4mg
Intervention descriptions: intervention 1: 1 mg IV dexamethasone will be pushed and miRNA levels will be checked at baseline just before injection and then at 15, 30, 45, and 60 minutes after injection.

Protocol documents:
ICF_001.pdf: 
IRB No:  Pro00057715/ Ame00023698 
Approval Date:  6/25/2019 
 
 
 
Page 1 of 11 
 
 
CONSENT FORM FOR RESEARCH 
 
Detection of miRNAs in HPA Axis Function in Healthy Subjects 
 
1. 
WHO IS CONDUCTING THIS RESEARCH STUDY?  
 
Principal Investigator:  
Anat Ben-Shlomo, MD, 310-423-7900 
 
After hours contact:  
 
Anat Ben-Shlomo, MD, 310-423-7900 
 
2. 
WHAT IS THE PURPOSE OF THIS RESEARCH STUDY? 
 
We are interested in collecting blood samples to examine the blood of healthy 
individuals after an injection of dexamethasone. Dexamethasone is a steroid that is 
very similar to cortisol, which is a hormone that is naturally released in response to 
stress. We have already tested the blood of mice and discovered specific genes that 
are related to the release of cortisol, and we would like to see if these genes can be 
found in humans too. 
 
You are a “healthy subject” research participant. A “healthy subject” means that 
you do not have the condition or disease that is being studied.  
 
Being asked to be part of a genetic study does not necessarily mean that you or 
other family members have a particular disorder or an inherited risk for a disorder. 
 
3. 
 HOW MANY PEOPLE WILL PARTICIPATE? 
 
About 20 people will take part in this study at CSMC.   
 
4. 
HOW LONG WILL I BE IN THE STUDY? 
 
We think you will be in the study for up to two hours, of which one hour is the 
length of time to complete the procedures in this study. Please see the section 
“What Study Procedures Are Involved?” for additional information. 
 
 


IRB No:  Pro00057715/ Ame00023698 
Approval Date:  6/25/2019 
 
 
 
Page 2 of 11 
5. 
WHAT STUDY PROCEDURES ARE INVOLVED? 
 
This section provides a summary of the procedures if you take part in this research 
study. 
 
Access to a vein in your arm will be established prior to performing the test. The 
dexamethasone will be delivered into and blood will be drawn from this vein. 
Approximately 12 mL (2.5 teaspoons) of blood will be drawn before the 
dexamethasone is injected and then every 15 minutes over the course of 1 hour. A 
total of 60 mL (about 12.5 teaspoons) will be drawn during the study.  
 
The samples taken from you will be collected solely for research purposes. This 
sample would otherwise not be taken if you did not participate in this research 
study. 
 
6. 
WHAT WILL MY SAMPLE BE USED FOR? 
 
DNA and RNA are the substances in our cells inherited from our parents.  They 
contain “genes” which can predict physical traits (e.g., eye and hair color, height, 
etc.). They also direct the body to produce certain proteins and hormones used in 
normal functioning. We will isolate DNA and/or RNA from your sample and test it 
to see if we can find the gene(s) that are involved in the production of the hormone 
cortisol. 
 
Genes can also have a role in a person’s risk for certain illnesses or disorders. We 
are not analyzing your genes to detect any illness or disorder. 
 
Specimens collected for this study may be valuable for scientific, research, 
teaching purposes, or developing a new medical product. By agreeing to participate 
in this research, you are donating the specimens to CSMC and authorizing CSMC 
and members of its staff to use your specimens for these purposes. After they are 
donated, CSMC or its designee will have exclusive rights to these specimens 
including any products, tests, discoveries, benefit or other interest coming from the 
specimens.   
 
CSMC may keep these research samples indefinitely or until the samples are all 
gone. These samples are not available for clinical (diagnostic) purposes.  
Therefore, if you wish to have any diagnostic testing done in the future, as a result 
of this or other research, it must be performed using a new sample.  
 


IRB No:  Pro00057715/ Ame00023698 
Approval Date:  6/25/2019 
 
 
 
Page 3 of 11 
7. 
WILL I RECEIVE INFORMATION ABOUT MY SAMPLES? 
 
The research tests done in this study are performed in a research only lab (not a 
certified clinical lab) where the results are intended for research purposes only. 
Therefore, we will not inform you of the test results obtained from this study or 
include them in your Cedars-Sinai medical record. 
 
Unanticipated Incidental Findings 
If, unexpectedly, we find that results of your research procedures could suggest 
important medical information and we determine there is something you or your 
doctors can do in response to this finding, we will contact you using the last 
contact information provided by you. If necessary, we may recommend additional 
clinical testing to confirm the research finding. The cost of any additional testing 
and any related treatment will be your responsibility. 
 
 
8. 
WHAT ARE THE POSSIBLE RISKS OR DISCOMFORTS?   
 
Risks of Dexamethasone may include the following, some may be serious 
 
• Fatigue 
• Nausea 
• Vomiting 
• Fever 
• Abdominal pain 
• Increased appetite  
• Rash 
• Dizziness 
• Trouble breathing 
• Mental/mood swings 
• Unusual hair/skin growth 
• Muscle pain/cramps 
• Easy bruising/bleeding 
• Insomnia 
• Bone/joint pain 
• Vision problems 
• Higher blood pressure, retaining water, changes in salt or potassium levels in 
your body 


IRB No:  Pro00057715/ Ame00023698 
Approval Date:  6/25/2019 
 
 
 
Page 4 of 11 
• Allergic reactions, such as itching or hives, swelling in your face or hands, 
swelling or tingling in your mouth or throat, chest tightness, trouble breathing 
 
Intravenous (IV) lines: 
You will receive the study drug and have blood drawn through an intravenous (IV) 
line. An IV line is a small tube that is attached to a catheter and inserted by needle 
into a vein usually in your hand or arm.  Qualified medical professionals will place 
IV lines for use in this study. 
 
IV lines are usually safe and well tolerated and complications are rare, but can 
include phlebitis (swelling of the vein) and infection.  The IV may come out 
accidentally or blood may leak around the line.  If the IV is not in the vein, 
medication or fluid can enter the surrounding soft tissues, and can be associated 
with swelling, discomfort, bruising and irritation.  Rarely, a clot can develop in the 
IV line itself.  If this happens, the staff may remove the old IV line and start a new 
IV line.  There is also a small risk of feeling lightheaded and fainting. 
 
Blood Draw 
Blood drawing may cause some pain and has a small risk of bleeding, bruising, or 
infection at the puncture site. There is also a small risk of fainting. 
 
Genetic Studies 
Genetic studies have raised concern as to whether the studies would place research 
subjects at risk for discrimination based on genetics. The federal Genetic 
Information Nondiscrimination Act (GINA) was passed to address this 
concern.  GINA makes it illegal for medical insurance companies and most 
employers to discriminate based on genetic information. The protections of GINA 
do not apply to life, disability, or long-term-care insurance. Although there are 
substantial protections against the risk of discrimination, you should be aware of 
this general concern. 
 
We try to protect all research subjects from placing them in a position where 
sensitive information could be disclosed that could lead to discrimination or the 
misuse of their information. This consent describes how your identifiable 
information will be protected under “How Will My Private Information Be Kept 
Confidential?” In addition, information for this genetic research study is kept 
separate from the hospital medical records and will not be put in the official 
Cedars-Sinai medical record by research staff. 
 
Reproductive and Lactation Risks  


IRB No:  Pro00057715/ Ame00023698 
Approval Date:  6/25/2019 
 
 
 
Page 5 of 11 
Taking part in this research study can affect an unborn baby.  Therefore, you 
should not participate in this study if you believe you may be pregnant.   
 
Women should not breastfeed a baby while on this study.   
 
The following paragraph is required if the research involves women of child-
bearing potential and the safety profile of the study drug or device, or study 
procedure, (such as, radiation, etc.) in pregnancy is unknown. 
 
Unknown Risks to the Developing Embryo or Fetus (an unborn baby) 
If you are pregnant during participation in this research, the study drug might 
involve risks to an embryo or fetus, which are currently unknown.  It is important 
that you contact the researcher immediately if you believe you might be pregnant. 
 
Unknown Risks 
In addition to the risks described above, there may be other discomforts or risks to 
you which are presently not foreseeable.  Many side effects may go away shortly 
after the study medication or procedure is stopped.  However, in some cases they 
can be serious or long-lasting. 
 
9. 
WHY WOULD MY PARTICIPATION BE STOPPED? 
 
The investigator may decide to take you off this research study, even if you would 
like to continue. Some common examples of why investigators might take research 
participants off research include the following: funding for the research is stopped; 
the whole study is stopped or modified at CSMC or at all sites for any reason; or 
the research participant is unable to comply with the protocol procedures. 
 
You may decide to stop the procedures described in the section “What Study 
Procedures Are Involved?” at any time. You may also request that the researchers 
stop using your samples if all of the following conditions are met at the time of 
your request: (1) your samples haven’t been used up; and (2) they can still be 
linked to you (e.g., the researchers haven’t removed identifying information from 
the samples). Otherwise, you will not be able to withdraw your sample, since it 
will no longer be identifiable. 
 
10. 
ARE THERE DIRECT BENEFITS IN TAKING PART IN THE 
STUDY? 
 
You should not expect to benefit from taking part in this research study. 


IRB No:  Pro00057715/ Ame00023698 
Approval Date:  6/25/2019 
 
 
 
Page 6 of 11 
 
11. 
HOW CAN MY PARTICIPATION BENEFIT OTHERS? 
 
While no benefit is ever guaranteed, we hope the information learned from this 
research study will benefit individuals in the future by helping us to learn which 
genes are associated with cortisol production.   
 
12. 
ARE THERE ANY OTHER OPTIONS? 
 
You may choose to not participate in this study. Your medical care will not be 
changed in any way as a result of this decision. 
 
 
13. 
HOW WILL MY PRIVATE INFORMATION BE KEPT 
CONFIDENTIAL? 
 
We will do our best to make sure that the personal information collected as part of 
this study is kept private.  However, we cannot guarantee total privacy.  A copy of 
your research consent and authorization forms may be filed in your electronic 
medical record at CSMC.  Your personal information may be given out if required 
by law.  If information from this study is published or presented at scientific 
meetings, your name and other identifiable personal information will not be used. 
Organizations that may look at and/or copy your medical records for research 
oversight, quality assurance, and data analysis include: accrediting agencies, 
government and regulatory groups (such as Food and Drug Administration (FDA), 
Office for Human Research Protections (OHRP), etc.), safety monitors, companies 
that sponsor the study, and authorized representatives of the sponsor.  
 
You will be asked to sign a separate “Authorization Form” that outlines who your 
information may be shared with for the purposes of this research and under what 
circumstances.   
 
14. 
WHAT ARE THE COSTS OF TAKING PART IN THIS STUDY? 
 
You and your insurance company will not be charged for your participation in this 
research study. 
 
15. 
WILL I BE PAID? 
 
You will receive a $25 gift card to Target for your participation.  
 


IRB No:  Pro00057715/ Ame00023698 
Approval Date:  6/25/2019 
 
 
 
Page 7 of 11 
16. 
WHAT IF I BECOME ILL OR INJURED BECAUSE OF TAKING 
PART IN THIS STUDY? 
 
Contact your study doctor at once, if you feel that you are ill or have been injured 
because of taking part in this study. If it is a medical emergency, call 911 or go to 
an emergency room. Promptly notify your study doctor of your situation at the 
phone number listed on page 1 of this consent form. 
 
Who pays for my research related illness or injury? 
A research-related injury or illness is a direct result of the Study Drug or a 
procedure performed only as a part of the study and is not part of your standard 
clinical medical treatment. Injury or illness related to or caused by non-research-
related activities (such as treatment provided outside of this study) would not be 
considered research-related.  If you are being treated for a research-related injury 
or illness, you will not pay for the costs of your appropriate medical care provided 
at CSMC or in any emergency room.   Cedars-Sinai may, however, ask for 
reimbursement where allowed from parties such as your health plan.  If you choose 
to obtain non-emergency care elsewhere, you or your health plan may be 
responsible for the costs of that care.  CSMC has no plans to pay for losses such as 
lost wages or pain or suffering.  You do not waive any of your legal rights by 
signing this form. 
 
17. 
WHAT IF I HAVE QUESTIONS OR PROBLEMS? 
 
If you have questions or concerns about this research, please contact the Principal 
Investigator or one of the co-investigators listed under “Who is conducting this 
research study?” on the first page of this consent form.   
 
If you have questions regarding your rights, concerns, or complaints about taking 
part in this study, please contact: 
 
CSMC Institutional Review Board (IRB) 
Phone: (310) 423-3783 
Email: ResearchConcerns@cshs.org 
 
The CSMC IRB has been established to review, approve, and monitor all human 
research at CSMC with the purpose of minimizing risks and protecting the rights 
and welfare of research participants. 
 
18. 
CONSENT PROVISIONS  
 


IRB No:  Pro00057715/ Ame00023698 
Approval Date:  6/25/2019 
 
 
 
Page 8 of 11 
If you sign this form below, it means that:   
 
(1) You have carefully read and understood the information presented in this 
informed consent form;  
(2) The information concerning the research study and its involved procedures 
has been fully explained to you and your questions have been answered to your 
satisfaction;  
(3) You have received all of the information you desire regarding your 
participation in the research study;  
(4) You have considered the potential risks, anticipated benefits and alternatives 
(and their relative risks and benefits) of participation; 
(5) You are voluntarily agreeing to participate in this research study; 
(6) For research where you will receive treatment or diagnostic intervention, you 
agree that your right to access copies of health information created during your 
participation in your research will be suspended while the research study is in 
progress; your right to access this information will be restored upon completion of 
the entire study; 
(7) You understand that by consenting to participate in the research, you are not 
giving up any of your legal rights; and 
(8) You have been provided with a copy of the “Experimental Subject’s Bill of 
Rights”, if applicable to this research study, and have been provided with an 
opportunity to ask questions regarding the Bill of Rights. 
 
If you have any additional questions during the course of your involvement in the 
research, please contact the investigator(s) and/or the IRB Office at any time. 
 
We will give you a copy of this signed and dated consent form and a signed copy 
of the Experimental Subject’s Bill of Rights. 
 
 


IRB No:  Pro00057715/ Ame00023698 
Approval Date:  6/25/2019 
 
 
 
Page 9 of 11 
 
SIGNATURE BY THE SUBJECT: 
 
 
 
 
 
 
 
Name of Subject (Print) 
Signature of Subject 
Date of Signature 
 
SIGNATURE BY THE INVESTIGATOR: 
 
I attest that all the elements of informed consent described in this form have been 
discussed fully in non-technical terms with the subject.  I further attest that all 
questions asked by the subject were answered to the best of my knowledge. The 
subject has been provided with the Experimental Subject’s Bill of Rights. 
 
 
 
 
 
 
 
 
       
  
Printed Name of Investigator 
 
 
 
 
 
Signature of the Investigator Who Obtained Consent 
Date of Signature 
 
 
SIGNATURE BY THE INTERPRETER/WITNESS 
(Signature of an interpreter is only required when a non-English speaking subject 
is consented with the assistance of an interpreter and an IRB-approved ‘short 
form.’  The witness may be any person who is conversant in both English and the 
language of the Non-English speaking subject, such as the interpreter (the 
certified hospital interpreter), study staff, a family member, or other person.  The 
witness signs the consent forms to confirm that the oral interpretation occurred.) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Name of Witness (Print) 
Signature 
Date Signed 
 


IRB No:  Pro00057715/ Ame00023698 
Approval Date:  6/25/2019 
 
 
 
Page 10 of 11 
 
EXPERIMENTAL SUBJECT’S BILL OF RIGHTS 
In accordance with California Health and Safety Code 24172, any person who is 
required to consent to participate as a subject in a research study involving a 
medical experiment or who is requested to consent on behalf of another has the 
right to: 
 
1. 
Be informed of the nature and purpose of the experiment. 
 
2. 
Be given an explanation of the procedures to be followed in the medical 
experiment, and any drug or device to be utilized. 
 
3. 
Be given a description of any attendant discomforts and risks to the subject 
reasonably to be expected from the experiment. 
 
4. 
Be given an explanation of any benefits to the subject reasonably to be 
expected from the experiment, if applicable. 
 
5. 
Be given a disclosure of any appropriate alternative procedures, drugs or 
devices that might be advantageous to the subject, and their relative risks 
and benefits. 
 
6. 
Be informed of the avenues of medical treatment, if any, available to the 
subject after the experiment if complications should arise. 
 
7. 
Be given an opportunity to ask any questions concerning the experiment or 
the procedure involved. 
 
8. 
Be instructed that consent to participate in the medical experiment may be 
withdrawn at any time and the subject may discontinue participation in the 
medical experiment without prejudice. 
 
9. 
Be given a copy of any signed and dated written consent form used in 
relation to the experiment. 
 
10. 
Be given the opportunity to decide to consent or not to consent to a medical 
experiment without the intervention of any element of force, fraud, deceit, 
duress, coercion, or undue influence on the subject's decision. 
 
 
 
___________________       _                     
___________________ 
Signature of Experimental Subject  
      Date 


IRB No:  Pro00057715/ Ame00023698 
Approval Date:  6/25/2019 
 
 
 
Page 11 of 11 
Distribution instruction for investigators: 
 
The signed (i) Consent form, (ii) Authorization for Use and Disclosure of 
Identifiable Health Information and (iii) "Experimental Subject's Bill of Rights" 
(the latter required if the research study involves medical interventions)* should 
be distributed to: 
 
1) Subject 
2) Principal Investigator’s research records (original) 
 
  
 
 

Prot_000.pdf: 
06.06.19, Anat Ben-Shlomo 
Detection of miRNAs in HPA axis function in healthy subjects 
 
Detection of miRNAs in HPA axis function in healthy subjects 
Background 
Cortisol is a steroid hormone involved in metabolism, inflammation and stress response (1). 
It is secreted by the adrenal glands in a pulsatile fashion in response to a feedback loop involving 
the hypothalamus-pituitary-adrenal (HPA) axis. Corticotropin-releasing hormone (CRH) is 
secreted from the hypothalamus in response to circadian rhythm changes and in response to 
stressors. CRH stimulates corticotroph cells in the anterior pituitary gland to secrete 
adrenocorticotropic hormone (ACTH), which, in turn, promotes synthesis of corticosteroids such 
as cortisol in the adrenal glands. Secretion of cortisol from the adrenal gland then downregulates 
hypothalamic CRH and pituitary ACTH secretion through feedback inhibition.  
Cortisol stimulation is used to assess the adequacy of HPA axis functional response in 
humans. However, accurate cortisol measurements can be misleading, especially in the presence 
of pituitary and hypothalamic diseases affecting HPA axis response. New biomarkers for HPA 
axis function are needed.   
We recently showed significant changes in miRNA expression profiles in the serum of 
humans and mice during HPA axis regulation and identified miRNA that might be useful as 
biomarkers of HPA axis function. We found that miRNA levels are significantly decreased 30 
minutes after ACTH stimulation in mice and humans, while dexamethasone increases serum 
miRNAs in mice.  
The proposed study will test dexamethasone effect on miRNA profile in healthy humans. As 
our data indicate that miRNA levels change over time, we will study the time course of miRNA 
response to 1 mg IV dexamethasone within 60 minutes after injection.  
Dexamethasone is used routinely in human subjects for the treatment of inflammatory 
conditions and as a diagnostic tool in the evaluation of excess cortisol secretion (Cushing’s 
syndrome). For the latter, 1 mg dexamethasone is given orally at midnight. However, oral 
formula absorption in the gut can range from 20 to 60 minutes due to the presence of food and 
other factors. IV administration will bypass this variability and ensure an accurate and 
reproducible time-course study. 
We will compare miRNA expression before and after dexamethasone treatment. We will 
follow miRNA expression dynamics over a 1-hour time course to identify peak expression levels 
and to correlate miRNA expression with circulating dexamethasone levels. 
Dexamethasone and miRNA levels will be checked at baseline just before injection and then 
at 15, 30, 45, and 60 minutes after injection. Dexamethasone level is taken to verify treatment 
and to correlate it with miRNA expression. 
 
Definitions 
• miRNA (also called microRNA or miR), small sequences of RNA that bind and inhibit 
specific areas in the gene and regulate gene expression. Most of the miRNAs are 
intracellular, but some can be found in the circulation.  
• mRNA (messenger RNA), a nucleic acid polymer molecule transcribed from DNA that 
serves as a template for the synthesis of the specified protein. The level of mRNA 
indicates changes in gene expression. 
• Adrenal gland, an endocrine gland located above the kidney. It produces multiple steroid 
hormones, most importantly cortisol (or corticosterone in rodents) and aldosterone. Its 
inner core produces epinephrine and norepinephrine. 


06.06.19, Anat Ben-Shlomo 
Detection of miRNAs in HPA axis function in healthy subjects 
 
• Serum, the liquid portion of the blood after it has been allowed to clot. It is free of cells 
and platelets. 
• Plasma, the liquid portion of blood that has been prevented from clotting. It includes 
cells and WBC can be extracted from it. 
• Dexamethasone, a steroid hormone that belongs to the glucocorticoid steroid hormone 
group that also includes cortisol. It binds specifically to the glucocorticoid receptor to 
induce cellular and tissue outcomes similar to those seen with cortisol. It is use clinically 
to reduce inflammation and as a diagnostic tool for Cushing’s syndrome.  
• Cushing’s syndrome, a disorder caused by increased production of cortisol. Symptoms 
include increased appetite and weight gain, mood changes, trouble sleeping, nausea, 
upset stomach, easy bruising, swelling, hypertension, hyperglycemia, osteoporosis.   
 
 
Study Protocol 
 
Subjects 
Twenty subjects will be recruited from CSMC employees. No information will be gathered 
from subjects’ medical files. An email will be sent out to all members of the Endocrinology 
department, the Pituitary Center, and affiliated offices (physicians, scientists, technicians, nurses, 
administrators). Employee email addresses will be included as BCC so as not to reveal the 
distribution list. In this email, study staff will detail all planned procedures, inclusion/exclusion 
criteria, and potential side effects. Those who express interest in participating will be contacted 
by study staff, who will review with them the protocol and informed consent and confirm 
eligibility for enrollment. Study staff will not enroll subjects who directly report to them to 
mitigate the potential for coercion. 
 
Inclusion Criteria 
• Adults age ≥ 18 
 
Exclusion Criteria 
• Pregnancy 
• Presence of a disease that affects HPA axis function 
• Current use of medications that affect cortisol secretion, such as opioid pain medication, 
anti-fungal agents, anti-epileptic agents, and glucocorticoids, including hydrocortisone, 
prednisone, dexamethasone, steroid-containing inhalers, and steroid injected into the 
joints 
• History of adverse event related to use of glucocorticoids 
 
Procedures 
• All procedures will be performed at the CTRC by staff nurses. 
• A vein line will be inserted to allow for dexamethasone injection and for easier blood 
draws during the study. 
• A total of 60 mL will be taken from each subject, drawn into 10 red-cap tubes (6 mL 
each) at 5 time points over the course of the study. 


06.06.19, Anat Ben-Shlomo 
Detection of miRNAs in HPA axis function in healthy subjects 
 
• At baseline, before dexamethasone injection, blood will be drawn into 2 red cap tubes: 
one tube will be used to assess dexamethasone levels and one tube will be used to assess 
for miRNAs. 
• Immediately after baseline blood collection, 1 mg dexamethasone will be administered 
intravenously at a rate of 4 mg/min. 
• After injection, blood will be drawn at 15, 30, 45, and 60 minutes into 2 red cap tubes: 
one tube will be used to assess dexamethasone levels and one tube will be used to assess 
for miRNAs. 
• After the 60-minute blood draws, the IV line will be removed, and the subject will be free 
to leave the facility. 
 
Adverse Effects 
We have extensive experience with the oral dexamethasone 1 mg diagnostic test for 
Cushing’s syndrome. We expect no new side effects with this same single dose administered 
intravenously. Side effects commonly associated dexamethasone are observed with higher doses 
and longer use of this medication. These effects mimic symptoms of Cushing’s syndrome and 
include swelling, increased appetite, weight gain, mood changes, trouble sleeping, nausea, upset 
stomach, easy bruising, hypertension, and hyperglycemia. 
We expect no adverse events from the blood draws. 
 
Blood Processing 
• Red-cap tubes used to collect blood to assess dexamethasone levels will be sent to the 
CSMC Quest laboratory. 
• Red-cap tubes used to collect blood to assess for miRNAs will be put on ice and hand-
delivered by study staff to Dr. Shlomo Melmed’s laboratory (Davis 3024) for serum 
extraction. 
o Serum will be stored in -80°C freezer. 
o Analysis of miRNAs will be done as one batch on all samples collected. 
 
 
Data Collection and Storage 
• Subject name, age, and sex will be recorded by study staff. 
• At CTRC, blood draw tubes will be coded using the subject’s initials and the day of 
collection. For example, blood from John Adam Smith collected on April 24, 2018, 
would be coded as J04A24S18. If the middle name is not available, there will be no letter 
in the fourth position. 
• This same code will also be used during sample processing and analysis. 
• Subjects will be identified only on the PI’s personal computer at CSMC. 
• Data will be stored for 5 years and will be accessible only to the PI. 
 
Compensation 
Subjects will be compensated with a $25 Target gift card. 
 
 
REFERENCES 


06.06.19, Anat Ben-Shlomo 
Detection of miRNAs in HPA axis function in healthy subjects 
 
1. 
Stewart P, Newell-Price, JDC. The adrenal cortex. In: Melmed S, et al, eds. Williams 
Textbook of Endocrinology, 13th ed. Philadelphia, PA: Elsevier; 2016. 
2. 
Yamamoto M*, Ben-Shlomo A*, Kameda H, et al. Somatostatin receptor subtype 5 
modifies hypothalamic-pituitary-adrenal axis stress function. JCI Insight. 2018;3:e122932. 
*Equal contribution. 
3. 
Altuvia Y, Landgraf P, Lithwick G, et al. Clustering and conservation patterns of human 
microRNAs. Nucleic Acids Res. 2005;33:2697-2706.