Clinical trial NCT03065218
Conditions: Thyroid Cancer
Keywords: Thyroid sestamibi
Sponsor: Medstar Health Research Institute
Start date: 2016-10-01; Completion date: 2021-02-15
Enrollment: 4 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This study is being done to see if the radioisotope 99mTc sestamibi scans can locate what is causing the elevated serum thyroglobulin in persons with differentiated thyroid cancer who have elevated serum thyroglobulin levels and negative diagnostic imaging tests.

This is for patients with:

* Elevated suppressed or stimulated thyroglobulin level (Tg) \> 10 ng/ml with or WITHOUT thyroglobulin antibodies ,
* All NEGATIVE standard diagnostic clinical imaging studies (NSDCIS) = negative ultrasound (US), diagnostic radioiodine scan (DRS), chest-x-ray (CXR), computer tomography with or without contrast (CT), and 18F-Fluoro-deoxyglucose positron emission computer tomography scan (18F-FDG PET) within the last 12 mos.
* If EDCIS (extensive diagnostic clinical imaging studies of 18F-sodium fluoride positron emission computer tomography scan (18F NaF PET) or 99mTc methylene diphosphonate bone scan (99mTc MDP), AND negative brain CT or magnetic resonance (MR) are performed, these are also negative.

Voluntary patients will have sestamibi scan performed in 4 phases:

Phase 1: receive an injection into their vein of a radioisotope called 99mTc sestamibi.

Phase 2: wait for 60 to 90 minutes in a waiting room

Phase 3: imaged lying face up on an imaging table while a camera passes around you from the top of the head to approximately the level of knees. This requires approximately 45 minutes

Phase 4: images will be reviewed by the nuclear medicine physician. This will take \~10-15 minutes. If additional images are required to clarify an image, then additional images of that area will be performed on the same camera or an alternate camera. As earlier, the additional images performed lying face up. These images require \~20-45 minutes. The patient will then be released.

The risk of this study is considered very low, and the potential benefits to the patient are considered very high.

Detailed description:
This study is being done to see if the radioisotope 99mTc sestamibi scans can locate what is causing the elevated serum thyroglobulin in persons with differentiated thyroid cancer who have elevated serum thyroglobulin levels and negative diagnostic imaging tests.

This is for patients with:

* Elevated suppressed or stimulated thyroglobulin level (Tg) \> 10 ng/ml with or WITHOUT thyroglobulin antibodies ,
* All NEGATIVE standard diagnostic clinical imaging studies (NSDCIS), which includes all the following negative studies: ultrasound (US), diagnostic radioiodine scan (DRS), chest-x-ray (CXR), computer tomography with or without contrast (CT), and 18F-Fluoro-deoxyglucose positron emission computer tomography scan (18F-FDG PET) within the last 12 mos.
* If NSDCIS and negative brain CT or magnetic resonance (MR) are performed and are negative, voluntary patients will have 99mTc sestamibi scan performed in 4 phases:

Phase 1: receive an injection into their vein of a radioisotope called 99mTc sestamibi.

Phase 2: wait for 60 to 90 minutes in a waiting room

Phase 3: imaged lying face up on an imaging table while a camera passes around you from the top of the head to approximately the level of knees. This requires approximately 45 minutes

Phase 4: images will be reviewed by the nuclear medicine physician. This will take \~10-15 minutes. If additional images are required to clarify an image, then additional images of that area will be performed on the same camera or an alternate camera. As earlier, the additional images performed lying face up. These images require \~20-45 minutes. The patient will then be released.

Interpretation of 99mTc sestamibi Study.

A. A team of two blinded nuclear medicine physicians will interpret the 99mTc sestamibi, and any area of radioactivity will be graded as by a standard nuclear medicine grading system:

1. Normal physiological activity
2. Probably physiological activity
3. Indeterminate activity
4. Probably metastatic disease
5. Metastatic disease

B. Criteria for "final determination" regarding whether a finding represents physiological activity or metastatic disease:

1. For findings graded as 1 or 2, they will be defined for this study as physiological activity.
2. For findings graded as 3, or 4, the following will be required:

i. Biopsy; however, this will only performed if clinically indicated.

1\. Follow-up: It is anticipated that very few biopsies will be performed and because the criteria for entering this study is NDCIS., the only alternative for confirming whether or not a foci of 99mTc sestamibi uptake on a scan is metastases will be follow up, which will be performed on a clinical basis. However, if on follow up any of the following occur, then the focus will be categorized as a metastases (true positive).

1. Subsequent biopsy,
2. Subsequent clinical imaging study(s) (For example, although a lytic bone lesion in the area of interested was not present initially on the CT, a lytic lesion indicative of metastases may subsequently develop in that area, and for this study this will be defined as evidence of metastases of DTC (true positive).

   ii. Blind I-131 treatment\*\* with or without a prefatory scan: If a "blind" I-131 treatment" is clinically selected and the post I-131 therapy scan demonstrates uptake in the same areas as the 99mTc sestamibi, then the finding on the 99mTc sestamibi will be classified for this study as a metastases of DTC.
3. Grade 5 is not anticipated, because unlikely I-131, which can have patterns that are very specific for DTC, 99mTc sestamibi patterns are not specific for DTC.

   * A "blind I-131 treatment" is a potential therapeutic option, and this term means that the treating physician or team cannot identify the source of the patient's elevated Tg, but because of factors such as the level of elevated Tg, the rate of rise of the Tg, and the patient's clinical situation, a therapeutic administration of I-131 is give despite being "blind" to the source of the Tg.

Arms: arm 1: 25 mCi 99mTc sestamibi intravenous injection, once. Then imaged for 45 minutes. More imaging might be required and this will be determined by a nuclear medicine physician onsite
Interventions: intervention 1: 99mTc sestamibi
Intervention descriptions: intervention 1: The administration of the diagnostic radioisotope, 99mTc sestambi, to image possible metastases in patients with differentiated thyroid cancer.

Protocol documents:
ICF_001.pdf: 
Office of Research Integrity
6525 Belcrest Rd, Suite 700
Hyattsville, MD 20782
Approval Notice
Continuation
31-Aug-2018
MedStar Washington Hospital Center
110 Irving Street NW
Washington, DC 20010

Protocol Number:
2016-166
PI Name:
Douglas Van Nostrand MD
Protocol Title:

Evaluation of 99mTc Sestamibi Scans In Patients who have Differentiated Thyroid Cancer,
 Elevated Serum Thyroglobulin Levels, and Negative Diagnostic Imaging Studies
Dear Douglas Van Nostrand MD,
The above-referenced Continuation submission was reviewed by IRB # 3 Washington in accordance with full board review
 procedures on 28-Aug-2018.
The IRB has approved the submission. You can begin research activities. The approval is valid from 28-Aug-2018
 through 27-Aug-2019. Any modifications to the IRB-approved protocol and other supporting documents must be reviewed
 and approved by the IRB prior to implementation. 
If the study will continue beyond 27-Aug-2019, please submit a continuation request form forty-five (45) days prior to 27-Aug-
2019 to allow the IRB sufficient time to review and approve the request.
If you have any questions, please contact me at 301-560-7338.
Thank you,
Timothy Rodriguez
Office of Research Integrity
Enclosure: IRB Stamped Informed Consent
IRB Stamped HIPAA Waiver


IRB number: 
2016-166 
Clinical Site IC Version:  
 
Project Title:   
Evaluation of 99mTc Sestamibi Scans in Patient Who Have Differentiated Thyroid Cancer, 
Elevated Serum Thyroglobulin Levels, and Negative Diagnostic Imaging Studies 
 
Principal Investigator: 
Douglas Van Nostrand 
Institution: 
MedStar Washington Hosp Ctr 
 
 
Consent To  Participate In A  
MedStar  Health Research 
Institute  
Clinical Research Study 
 
Page 1 of 8 
 
 
Participant Initials _______ 
 
IRB Approval Stamp 
MedStar Health Research Institute 
 
APPROVAL DATE 08/28/2018 
APPROVAL EXPIRES 08/29/2019 
 
IRB APPROVED 
 
 
MedStar Health Research Institute Informed Consent for Clinical 
Research 
  
INTRODUCTION 
 
We invite you to take part in a research study called “Evaluation of 99mTc Sestamibi Scans In Patients who Have 
Differentiated Thyroid Cancer, Elevated Serum Thyroglobulin Levels, and Negative Diagnostic Imaging Studies.”  
You were selected as a possible participant in this study because you have thyroid cancer and an elevated serum 
thyroglobulin level and all of your standard diagnostic imaging studies have been unable to identify the source of this 
elevation.  Please take your time to read this form, ask any questions you may have and make your decision.  We 
encourage you to discuss your decision with your family, friends and your doctor(s).   
 
WHAT IS THE PURPOSE OF THIS STUDY? 
 
This study is being done to see if the radioisotope 99mTc sestamibi scans can locate what is causing the elevated serum 
thyroglobulin in persons with differentiated thyroid cancer who have elevated serum thyroglobulin levels and negative 
diagnostic imaging tests.  
 
WHAT ELSE SHOULD I KNOW ABOUT THIS RESEARCH STUDY? 
 
It is important that you read and understand several points that apply to all who take part in our studies: 
 
• 
Taking part in the study is entirely voluntary and refusal to participate will not affect any rights or benefits you 
normally have;  
• 
You may or may not benefit from taking part in the study, but knowledge may be gained from your participation 
that may help others; and 
• 
You may stop being in the study at any time without any penalty or losing any of the benefits you would have 
normally received. 
 
The nature of the study, the benefits, risks, discomforts and other information about the study are discussed further below.  
If any new information is learned, at any time during the research, which might affect your participation in the study, we will 
tell you.  We urge you to ask any questions you have about this study with the staff members who explain it to you and 
with your own advisors prior to agreeing to participate. 
 
WHO IS IN CHARGE OF THIS STUDY? 
 
The investigator is Douglas Van Nostrand, MD.  The research is being sponsored by the investigator.  
 
WHO CANNOT PARTICIPATE IN THIS STUDY? 
 


IRB number: 
2016-166 
Clinical Site IC Version:  
 
Project Title:   
Evaluation of 99mTc Sestamibi Scans in Patient Who Have Differentiated Thyroid Cancer, 
Elevated Serum Thyroglobulin Levels, and Negative Diagnostic Imaging Studies 
 
Principal Investigator: 
Douglas Van Nostrand 
Institution: 
MedStar Washington Hosp Ctr 
 
 
Consent To  Participate In A  
MedStar  Health Research 
Institute  
Clinical Research Study 
 
Page 2 of 8 
 
 
Participant Initials _______ 
 
IRB Approval Stamp 
MedStar Health Research Institute 
 
APPROVAL DATE 08/28/2018 
APPROVAL EXPIRES 08/29/2019 
 
IRB APPROVED 
 
 
You cannot be in this study if any of the following apply to you:  
• < 18 years of age, 
• Pregnant or breast feeding,  
• You have not had ALL of the following diagnostic imaging scans: 
• US (ultrasound),  
• CXR (chest-X-ray),  
• CT (computer tomography scan), and 
• PET scan (18F Fluoro-deoxyglucose positron emission tomography scan). 
• Any of the above diagnostic imaging scans identifying a source of the elevated serum 
thyroglobulin level. 
• If any of the additional diagnostic imaging scans noted below  were performed and  identified 
a source of the elevated serum thyroglobulin level 
• 
18F NaF PET bone scan (18F sodium fluoride positron emission tomography bone scan) 
• Bone scan  (99mTc methylene diphosphonate or other equivalent bone agent )  
• Brain scan (Computer tomography or magnetic resonance imaging) 
• Not diagnosed with differentiated thyroid cancer 
 
WHAT IF I AM PRESENTLY PARTICIPATING IN ANOTHER RESEARCH STUDY? 
 
Are you presently participating in any other research studies?  
Yes 
   
No 
 
 
If yes, please state which study(ies)____  
 
 
 
 
 
 
 
While participating in this study, you should not take part in any other research project without approval from the 
people in charge of each study.  This is to protect you from possible injury arising from such things as extra blood 
drawing, extra x-rays, interaction of research drugs, or similar hazards. 
 
HOW MANY PEOPLE WILL TAKE PART IN THE STUDY? 
 
About 15 people will take part in this study, worldwide.  15 people will be recruited at this site. 
 


IRB number: 
2016-166 
Clinical Site IC Version:  
 
Project Title:   
Evaluation of 99mTc Sestamibi Scans in Patient Who Have Differentiated Thyroid Cancer, 
Elevated Serum Thyroglobulin Levels, and Negative Diagnostic Imaging Studies 
 
Principal Investigator: 
Douglas Van Nostrand 
Institution: 
MedStar Washington Hosp Ctr 
 
 
Consent To  Participate In A  
MedStar  Health Research 
Institute  
Clinical Research Study 
 
Page 3 of 8 
 
 
Participant Initials _______ 
 
IRB Approval Stamp 
MedStar Health Research Institute 
 
APPROVAL DATE 08/28/2018 
APPROVAL EXPIRES 08/29/2019 
 
IRB APPROVED 
 
 
WHAT HAPPENS IF I AGREE TO BE IN THE STUDY? 
 
 The following procedures will be done within the Division of Nuclear Medicine at MedStar Washington Hospital Center on 
an outpatient basis. 
 
Preparation:  none 
 
Phase 1:  You will receive an injection into your vein of a radioisotope called 99mTc sestamibi.  
 
Phase 2:  You will wait for 60 to 90 minutes in a waiting room 
 
Phase 3:  You will then be imaged lying face up on an imaging table while a camera passes around you from the top of 
your head to approximately the level of your knees.  This requires approximately 45 minutes 
 
Phase 4:  Your images will be reviewed by the nuclear medicine physician.  This will take ~10-15 minutes.  If additional 
images are required to clarify an image, then additional images of that area will be performed.  As earlier, you will have the 
additional images performed with you lying face up.  These images require ~20-45 minutes.  You will then be released 
 
 
• 
The following procedure is part of the research study and would not normally be done as part of your routine care:  
• 
99mTc sestamibi scan. 
 
 
HOW LONG WILL I BE IN THE STUDY? 
 
If the 99mTc sestamibi scan does not suggest a possible source for the elevated thyroglobulin, you will be in the study one 
day.   
 
If the 99mTc sestamibi scan does suggest a possible source for the elevated serum thyroglobulin, you may be in the study 
for a longer period of time in order for the study doctor to follow up with you regarding further evaluation and/or treatment 
of the possible source of elevated serum thyroglobulin.   The follow-up is part of the study and will be made over the phone 
at 1, 3, 6 and 12 months after the research scan and/or until diagnosis of the metastatic site.  The actual evaluation and/or 
treatment itself for the possible source of elevated serum thyroglobulin is not part of the research study.  
 
The investigator may decide to take you off this study if it is believed to be in your best interest, you fail to follow 
instructions, new information becomes known about the safety of the study, or for other reasons the investigator or 
sponsor believes are important. 
 
You can stop participating at any time.  However, if you decide to stop participating in the study, we encourage you to talk 
to the investigator and your regular doctor first so they can help you decide what other options may be best for your 
medical care once you are off study. 


IRB number: 
2016-166 
Clinical Site IC Version:  
 
Project Title:   
Evaluation of 99mTc Sestamibi Scans in Patient Who Have Differentiated Thyroid Cancer, 
Elevated Serum Thyroglobulin Levels, and Negative Diagnostic Imaging Studies 
 
Principal Investigator: 
Douglas Van Nostrand 
Institution: 
MedStar Washington Hosp Ctr 
 
 
Consent To  Participate In A  
MedStar  Health Research 
Institute  
Clinical Research Study 
 
Page 4 of 8 
 
 
Participant Initials _______ 
 
IRB Approval Stamp 
MedStar Health Research Institute 
 
APPROVAL DATE 08/28/2018 
APPROVAL EXPIRES 08/29/2019 
 
IRB APPROVED 
 
 
 
If you suddenly withdraw from the study, there are no consequences, but we may not be able to use any of the information 
gathered from your participation. 
 
WHAT ARE THE RISKS AND SIDE EFFECTS OF THIS STUDY? 
 
If you decide to participate in this study, you should know there may be risks.  You should discuss these with the 
investigator and/or your regular doctor and you are encouraged to speak with your family and friends about any potential 
risks before making a decision.  Potential risks and side effects related to this study include: 
 
Potential risks and side effects that may occur include: 
 
1. Chemical:  You will receive radioactive sestamibi in very small amounts.  Tracer doses do not have 
pharmacologic effects; however, less than 0.5 % of patients have reported the following side effects :  
headache, abdominal discomfort, irregular heart beat, temporary joint pain, dizziness, vomiting, 
lightheadedness or fainting, allergic reaction with shortness of breath and decreased blood pressure and 
heart rate.  Flushing, swelling, injection site inflammation, fever, itching rash and hives have also been 
noted. 
 
2. Radiation exposure:  The total radiation exposure resulting from participation in this research study is 
estimated to be less1/100th (0.1) of the amount of radiation that you will receive if you have been or will be 
treated with I-131 for your thyroid cancer. In addition, the Food and Drug Administration regulates and 
limits the amount of radiation exposure to volunteers resulting from participating in a research study such 
as this to a level that it believes is acceptable. The FDA limit is 5 rem to any organ of the body for a 
research study such as this. The study meets the FDA requirement. 
 
3. Risks from blood drawing:  99mTc sestamibi will be injected into a vein in your arm using a needle as if 
drawing blood.  Injection may cause pain and bruising and, rarely, infection at the place where the injection 
is performed.  Sometimes the injection causes people to feel lightheaded or even faint.  
 
4. Claustrophobia (fear of closed spaces):  Some patients have reported a feeling of claustrophobia when 
being imaged by a nuclear medicine camera.  
 
5. False positive result: This is possible if the procedure incorrectly indicates that thyroid cancer is present in 
a particular location or if the sestamibi appears to find a possible source for thyroglobuling but the source 
actually does not exists.  A false positive result may result in unnecessary additional testing, biopsy and/or 
treatment. 
 
  
Please tell the investigator about all medications including over-the-counter drugs or herbal supplements you are taking, 
even if you don’t think they are important. 


IRB number: 
2016-166 
Clinical Site IC Version:  
 
Project Title:   
Evaluation of 99mTc Sestamibi Scans in Patient Who Have Differentiated Thyroid Cancer, 
Elevated Serum Thyroglobulin Levels, and Negative Diagnostic Imaging Studies 
 
Principal Investigator: 
Douglas Van Nostrand 
Institution: 
MedStar Washington Hosp Ctr 
 
 
Consent To  Participate In A  
MedStar  Health Research 
Institute  
Clinical Research Study 
 
Page 5 of 8 
 
 
Participant Initials _______ 
 
IRB Approval Stamp 
MedStar Health Research Institute 
 
APPROVAL DATE 08/28/2018 
APPROVAL EXPIRES 08/29/2019 
 
IRB APPROVED 
 
 
 
There may also be risks and side effects other than those listed above that we cannot predict.  Many side effects go away 
in a short time after the injection of the 99mTc sestamibi, but, in some cases, side effects can be serious, long lasting and/or 
life threatening.  If you have any unwanted side effects, you should ask the investigator what may be done to make the 
side effect less uncomfortable. 
 
For more information about risks and side effects, please ask Douglas Van Nostrand, MD.  
 
ARE THERE ANY BENEFITS TO TAKING PART IN THE STUDY? 
 
You may or may not benefit in participating in this study.   The 99mTc sestamibi scan may identify the source of your 
elevated serum thyroglobulin level that had not previously been identified by your physician or any of the other diagnostic 
imaging studies.  This may in turn potentially allow earlier treatment of a site of cancer before that site of cancer becomes 
a problem to you. 
 
However, you may not get any direct benefit from being in this study.  We cannot promise that you will experience any 
benefits from participating in this study.  We hope the information learned from this study will benefit others in the future. 
 
WHAT OTHER OPTIONS ARE THERE? 
 
Instead of being in this study, you have these options: 
 
• 
Continued active surveillance with no treatment intervention. 
 
• 
A therapy with 131I without knowing ahead of time whether or not there will be any uptake in any site of cancer or 
any benefit from that therapy.  
 
• 
A therapy with a tyrosine kinase inhibitor (TKI). A TKI is a drug that interferes with selected chemical processes in 
the cell that may or may not stabilize progressive metastatic disease. 
 
• 
You always have the option to not be in this study. 
 
WHAT ABOUT CONFIDENTIALITY? 
 
Your personal health information (PHI) will be kept private to the extent allowed by law.  Study records identifying you will 
be kept confidential and will not be made publicly available.  You will not be identified by name in any publications resulting 
from this study.  You will be asked to sign a separate form that will give permission to the investigator, representatives 
from government agencies, including the Food and Drug Administration (FDA), institutional review boards, the sponsor 
and/or the sponsor’s representative(s), and certain other people, agencies or entities, to look at and review the records 
related to this study including your personal health information and the information discovered during this study.  This 
separate form explains in greater detail who will have access to your records, what type of information will be reviewed 


IRB number: 
2016-166 
Clinical Site IC Version:  
 
Project Title:   
Evaluation of 99mTc Sestamibi Scans in Patient Who Have Differentiated Thyroid Cancer, 
Elevated Serum Thyroglobulin Levels, and Negative Diagnostic Imaging Studies 
 
Principal Investigator: 
Douglas Van Nostrand 
Institution: 
MedStar Washington Hosp Ctr 
 
 
Consent To  Participate In A  
MedStar  Health Research 
Institute  
Clinical Research Study 
 
Page 6 of 8 
 
 
Participant Initials _______ 
 
IRB Approval Stamp 
MedStar Health Research Institute 
 
APPROVAL DATE 08/28/2018 
APPROVAL EXPIRES 08/29/2019 
 
IRB APPROVED 
 
 
and for what purposes, how long your permission for others to review and release your records will last, and how you may 
withdraw your permission if necessary.  If you do not wish to sign this permission form you will not be allowed to participate 
in this study. 
 
A Data Safety and Monitoring Board, which is a group of experts not connected to the study, will be reviewing the data 
from this research throughout the study.   This Data Safety and Monitoring Board is the Radioactive Drug Research 
Committee.   We will tell you about any new information from this or other studies that may affect your health, welfare, or 
willingness to stay in this study. 
 
WILL I BE PAID FOR PARTICIPATING IN THIS STUDY? 
 
You will not be paid for being in this study.  
 
WHAT ARE THE COSTS? 
 
You do not have to pay anything to be in this study.  However, if taking part in this study leads to procedures for care not 
included in the study, it may lead to added costs for you or your insurance company.  You will not be charged the 99mTc 
sestamibi scan that is part of this research study.   
 
However, you, or your insurance company, will be charged for any other portion of your care that is considered standard of 
care.  You may be responsible for any co-payments and deductibles that are standard for your insurance coverage.  This 
may include any additional diagnostic tests, biopsies, follow up appointments, and/or therapies.  
 
WHAT IF I’M INJURED OR BECOME ILL DURING THE STUDY? 
 
We will make every effort to prevent injuries or illness from occurring while you are in the study.   In the case of an injury, 
illness, or other harm occurring to you during, or resulting from, the study, you should seek medical treatment.  You should 
also contact the study doctor as soon as possible.  You or your insurance company will be charged for any continuing 
medical care and/or hospitalization that are not a part of the study.   
If you suffer an injury related to the study drug or study procedures, the reasonable costs of necessary medical treatment 
of the injury will not be reimbursed by the principal investigator, MedStar Health Research Institute or MedStar 
Washington Hospital Center, MedStar Health or its affiliated entities to the extent these costs are not covered by your 
insurance or other third party coverage.   
 
No funds have been set aside, by  MedStar Washington Hospital Center, the MedStar Health Research Institute, MedStar 
Health, or its affiliated entities to repay you in case of injury, illness, or other harm occurring during, or resulting from the 
study, and their current policies do not provide for payments for lost wages, cost of pain and suffering, or additional 
expenses.  By agreeing to this you do not give up your rights to seek compensation in the courts. 
 
 
WHAT ARE MY RIGHTS AS A PARTICIPANT? 


IRB number: 
2016-166 
Clinical Site IC Version:  
 
Project Title:   
Evaluation of 99mTc Sestamibi Scans in Patient Who Have Differentiated Thyroid Cancer, 
Elevated Serum Thyroglobulin Levels, and Negative Diagnostic Imaging Studies 
 
Principal Investigator: 
Douglas Van Nostrand 
Institution: 
MedStar Washington Hosp Ctr 
 
 
Consent To  Participate In A  
MedStar  Health Research 
Institute  
Clinical Research Study 
 
Page 7 of 8 
 
 
Participant Initials _______ 
 
IRB Approval Stamp 
MedStar Health Research Institute 
 
APPROVAL DATE 08/28/2018 
APPROVAL EXPIRES 08/29/2019 
 
IRB APPROVED 
 
 
 
• 
You have the right to be told about the nature and purpose of the study;  
• 
You have the right to be given an explanation of  exactly what will be done in the study and given a description of 
potential risks, discomforts, or benefits that can reasonably be expected;  
• 
You have the right to be informed of any appropriate alternatives to the study, including, if appropriate, any drugs or 
devices that might help you, along with their potential risks, discomforts and benefits;  
• 
You have the right to ask any questions you may have about the study; 
• 
You have the right to decide whether or not to be in the study without anyone misleading or deceiving you; and  
• 
You have the right to receive a copy of this consent form.   
 
By signing this form, you will not give up any legal rights you may have as a research participant.  You may choose to not 
take part in or to leave the study at any time.  If you choose to not take part in or to leave the study, your regular care will 
not be affected and you will not lose any of the benefits you would have received normally.  We will tell you about new 
information that may affect your health, welfare, or willingness to be in this study. 
 
WHO DO I CALL IF I HAVE QUESTIONS OR PROBLEMS? 
 
For questions about the study or a research-related injury, contact the investigator, Douglas Van Nostrand at (telephone 
number 202-877-0300).  If you are having a medical emergency, you should call 911 or go directly to the nearest 
emergency room. 
 
For questions about your rights as a research participant, contact the MedStar Health Research Institute.  Direct 
your questions to the Office of Research Integrity at: 
 
Address: 
MedStar Health Research Institute 
 
Telephone: 
(301) 560-2912 
 
6525 Belcrest Rd. 
 
Toll Free: 
(800) 793-7175 
 
Suite 700 
 
Fax 
(301) 560-7336 
 
Hyattsville, MD 20782 
 
 
 
 
 
THIS SPACE INTENTIONALLY LEFT BLANK  


IRB number: 
2016-166 
Clinical Site IC Version:  
 
Project Title:   
Evaluation of 99mTc Sestamibi Scans in Patient Who Have Differentiated Thyroid Cancer, 
Elevated Serum Thyroglobulin Levels, and Negative Diagnostic Imaging Studies 
 
Principal Investigator: 
Douglas Van Nostrand 
Institution: 
MedStar Washington Hosp Ctr 
 
 
Consent To  Participate In A  
MedStar  Health Research 
Institute  
Clinical Research Study 
 
Page 8 of 8 
 
 
 
 
IRB Approval Stamp 
MedStar Health Research Institute 
 
APPROVAL DATE 08/28/2018 
APPROVAL EXPIRES 08/29/2019 
 
IRB APPROVED 
 
 
SIGNATURES 
 
As a representative of this study, I have explained the purpose, the procedures, the possible benefits and risks that are 
involved in this research study.  Any questions that have been raised have been answered to the individual’s satisfaction. 
 
 
_____________________________________________________________ 
__________________ 
Signature of Person Obtaining Consent 
 
 
 
 
 
Date of Signature 
 
Printed Name of Individual Obtaining Consent:  _________________________________ 
 
I, the undersigned have been informed about this study’s purpose, procedures, possible benefits and risks, and I have 
received a copy of this consent.  I have been given the opportunity to ask questions before I sign, and I have been told that 
I can ask other questions at any time.  I voluntarily agree to be in this study.  I am free to stop being in the study at any 
time without need to justify my decision and if I stop being in the study I understand it will not in any way affect my future 
treatment or medical management.  I agree to cooperate with Douglas Van Nostrand and the research staff and to tell 
them immediately if I experience any unexpected or unusual symptoms. 
 
 
___________________________________________________________  
________________ 
Participants signature 
 
 
 
 
 
 
 
Date of Signature 
 
Printed Name of Participant   ________________________________________ 
 
 
___________________________________________________________  
_________________ 
Signature of Witness 
(If applicable but not required)  
 
 
Date of Signature 
 
Printed Name of Witness:  __________________________________________ 
 
 
As the Principal Investigator (or designee) for this research study, I attest that the participant has voluntarily agreed to be 
part of this study, the risks and benefits of the study have been fully explained, and any questions have been addressed to 
the participant’s satisfaction. 
 
_________________________________________________________________________ _______________ 
Principal Investigator’s Signature   
 
 
 
 
 
 
Date of Signature 





















Prot_000.pdf: 
Evaluation of 99mTc Sestamibi Scans In Patients who have Differentiated 
Thyroid Cancer, Elevated Serum Thyroglobulin Levels, and Negative 
Diagnostic Imaging Studies  
Principal Investigator:  
Douglas Van Nostrand, MD 
Director, Nuclear Medicine Research 
MedStar Health Research Institute and Washington Hospital Center 
Suite GA60F 
110 Irving Street, N.W. 
Washington, DC 20010 
(202) 877-0300
Add co-investigators:  
Cristiane Gomes Lima 
Research Fellow 
MedStar Health Research Institute 
Di Wu 
Research Fellow 
MedStar Health Research Institute 
Version: 06 August 2019 
Introduction 
This is a prospective, informed consent study to evaluate a diagnostic radioisotope 
scan for evaluation of a selected group of patients who have differentiated thyroid cancer, 
elevated serum thyroglobulin levels indicating the presence of disease, but negative 


diagnostic imaging studies.   The following two sections are a layman’s and medical overview 
of this study, respectively.    
Layman’s Overview 
One of the major problem areas in the management of patients who have thyroid cancer 
that is differentiated (DTC) is when their blood levels of the tumor marker for this cancer 
(thyroglobulin) increase.   Yet, despite all the efforts of the physician with physical exam and 
the standard diagnostic imaging studies, the physician is unable to find the site of metastases 
that is causing this patient’s tumor marker to increase.   
One type of scan performed with an isotope called 99mTc sestamibi was evaluated in the 
1990s and 2000s in such patients and was found useful.  However, this scan was replaced 
with multiple superior imaging modalities such as Computer Tomography (CT) scan and 18F 
fluorodeoxyglucose positron emission tomography (PET) scan.   Unfortunately, these scans 
do not always identify the site of the metastases causing the patient’s tumor marker to 
increase.   To date we are unaware of any one who has evaluated 99mTc sestamibi when all 
these other standard and extensive imaging scans are also negative.  The purpose of this 
study is to determine if 99mTc sestamibi may have a role in localizing the tumor in the patients 
who have an elevated tumor marker with all standard diagnostic scans negative. 
Medical Overview 
 
Patients who have differentiated thyroid cancer with a positive or rising serum thyroglobulin 
level (Tg) and negative standard diagnostic imaging studies (NSDIS)* or negative extensive 
diagnostic imaging studies (NEDIS)** represent a diagnostically problematic group of patients.  The 
positive or rising Tg typically indicates the presence of recurrent metastatic DTC; however, with either 
NSDIS or a NEDIS, no structural or functional recurrent or metastatic disease accounting for the 
positive or rising Tg can be identified.   As a result, potential local treatment of a specific site of 
metastases is not an option and deciding whether to continue active surveillance or to perform a 
“blind” I-131 treatment is not resolvable by the data available.     
As a result, the physicians, in order to make a management decision, must use less than 
satisfactory factors such as patient age, level of Tg, doubling time of Tg, past patient history, patient 
co-morbidities, patient desires, etc.  Accordingly, additional methods to identify the source of the 
elevated or rising Tg levels are desirable.   
 
99mTc sestamibi has been previously used in the evaluation of differentiated thyroid cancer and 
is taken up by mitochondria in differentiated thyroid cancer cells [1-11].  Although good overall 
sensitive and specificity has been shown using 99mTc sestamibi, it is not routinely used because other 
standard diagnostic imaging studies have superior sensitivity, specificity, and/or localization of DTC 
cells.  However, to our knowledge no study has been published to evaluate the utility of 99mTc 
sestamibi when the other SDCIS or EDCIS are negative.  The objective of this study is to evaluate the 
utility of 99mTc sestamibi when either all SDIS or EDIS are negative.  


*Negative STANDARD diagnostic clinical imaging studies (NSDCIS) = negative ultrasound (US), diagnostic radioiodine 
scan (DRS), chest-x-ray (CXR), computer tomography with or without contrast (CT), and 18F-Fluoro-deoxyglucose 
positron emission computer tomography scan (18F-FDG PET). 
Negative neck structural imaging at least one of the following studies, (i.e., ultrasound, CT with or without 
contrast, MRI scan) was performed and all performed imaging studies must be negative. 
Negative chest structural imaging at least one of the following studies ( i.e., x-ray, CT, MRI) must be performed, 
and all performed imaging studies must be negative. 
Negative abdominal structural imaging at least one of the following studies (i.e., ultrasound, CT, MRI) must be 
performed and all performed imaging studies must be negative. 
Negative diagnostic radioiodine whole-body scan. 
Negative FDG PET/CT scan. 
**Negative EXTENSIVE diagnostic clinical imaging studies (NEDCIS) = all of the above plus negative 18F-sodium fluoride 
positron emission computer tomography scan (18F NaF PET) or 99mTc methylene diphosphonate bone scan (99mTc MDP), 
AND negative brain CT or magnetic resonance (MR). 
OBJECTIVE OF THE STUDY 
The primary objective of this prospective study is to:  
1. Perform a pilot study of the utility of the 99mTc sestamibi scans in patients who have 
differentiated thyroid cancer, positive serum thyroglobulin levels, and negative 
SDCIS* or negative EDCIS**.    
STUDY DESIGN AND METHODS 
 
This will be a prospective informed consent study. Medical records of the patients with 
histologically documented differentiated thyroid carcinoma (DTC) in follow-up at MedStar Washington 
Hospital Center will be reviewed via the electronic medical records systems such as Centricity and 
Amalga. The subjects meeting the following eligibility criteria may be included in the study. 
INCLUSION CRITERIA 
• ≥ 18 years of age; 
• Diagnosed with differentiated thyroid carcinoma; 
• At least one prior I-131 therapy, which may be remnant ablation, adjuvant treatment, and treatment 
of distant metastases, 
• Elevated suppressed or stimulated thyroglobulin level (Tg) ≥ 5 ng/ml WITHOUT thyroglobulin 
antibodies, 
• Any measurable suppressed or stimulated thyroglobulin (Tg) level WITH positive thyroglobulin 
antibodies, 


• All NEGATIVE standard diagnostic clinical imaging studies (NSDCIS) = negative ultrasound (US), 
diagnostic radioiodine scan (DRS), chest-x-ray (CXR), computer tomography with or without 
contrast (CT), and 18F-Fluoro-deoxyglucose positron emission computer tomography scan (18F-
FDG PET) within the last 24 months. 
▪ 
Negative neck structural imaging at least one of the following studies (i.e., ultrasound, CT with or 
without contrast, MRI scan) was performed and all performed imaging studies must be negative. 
▪ 
Negative chest structural imaging at least one of the following studies (i.e., x-ray, CT, MRI) must 
be performed, and all performed imaging studies must be negative. 
▪ 
Negative abdominal structural imaging at least one of the following studies (i.e., ultrasound, CT, 
MRI) must be performed and all performed imaging studies must be negative. 
▪ 
Negative diagnostic radioiodine whole-body scan. 
▪ 
Negative 18F FDG PET/CT scan. 
 
• If EDCIS (extensive diagnostic clinical imaging studies) of 18F-sodium fluoride positron 
emission computer tomography scan (18F NaF PET) or 99mTc methylene diphosphonate 
bone scan (99mTc MDP), AND brain CT or magnetic resonance (MR) are performed, these 
are also negative.  
 
• OR meets all of the above prior criteria, but has stable indeterminate nodule on CT for 6 
months. Stable defined by Recist Criteria version 1.1 as “Neither sufficient shrinkage to qualify 
for partial response (30% decrease) nor sufficient increase to qualify for progressive disease 
(20% increase), taking as reference the smallest sum diameters while on study.     
EXCLUSION CRITERIA 
• < 18 years of age; 
• Pregnant or breast feeding 
• Any SDCIS or EDCIS that is positive and/or suggestive of recurrent and/or distant metastases 
secondary to DTC.  If a study is indeterminate, this will be forwarded to a committee for review and 
resolution.  
DOCUMENTATION OF PREGNANCY TESTING OR WAIVER 
Potential female subjects of childbearing age will undergo either pregnancy testing with blood 
or urine HCG levels prior to study enrollment. 
Alternatively, female subjects can opt to sign a pregnancy waiver form if she rejects 
undergoing pregnancy testing prior to study enrollment. Pregnancy waiver form will be submitted to 
the IRB for approval. 
Per Cardinal Health Sestamibi Package Insert: “Pregnancy Category C. Animal reproduction 
and teratogenicity studies have not been conducted with Technetium Tc 99m Sestamibi. It is also not 
known whether Technetium Tc 99m Sestamibi can cause fetal harm when administered to a pregnant 
woman or can affect reproductive capacity. There have been no studies in pregnant women. 
Technetium Tc 99m Sestamibi should be given to a pregnant woman only if clearly needed.” 


STUDY POPULATION:  GENDER AND ETHNIC INCLUSION 
 
No potential participants will be excluded from participating in this study solely based on 
gender, ethnic origin, or socioeconomic status.  
SUBJECT RECRUITMENT AND SCREENING 
 
The patient’s will be identified by referring endocrinologists and nuclear medicine physicians.  
For potential candidates identified from referring endocrinologists, these will be referred for screening 
through either Tasha Peterson, Dr. Di Wu, Dr. Cristiane Lima, Shari Moreau, and/or Dr. Douglas Van 
Nostrand.  Potential candidates identified by the “reading desk” nuclear medicine physician will again 
be screened by Dr. Cristiane Lima, Shari Moreau, and/or Dr. Douglas Van Nostrand.  For potential 
candidates identified by the “reading desk” nuclear medicine physician that meet the criteria, the 
referring physician will be contacted regarding our desire to speak with the patient regarding this 
study.   
After the endocrinologists supports the patient potentially participating in the study and after 
confirming that the patient passes the first screening step, the patient will be contacted to explain the 
study.  If the patient is interested, the staff will give the patient an informed consent, and then a 
discussion with the patient will follow. After final confirmation that the patient meets all inclusion 
criteria without any exclusion criteria, informed consent will be obtained.  This study is being 
submitted as an exempt study (e.g. waiver of informed consent).  
IRB APPROVAL 
 
The study will submitted to the IRB and initiated only after IRB approval of all documents 
including the protocol, informed consent and HIPPA form.  
PATIENT DATA 
The demographic, pathological, laboratory, imaging, therapy data, outcome data, etc. will be 
obtained using the electronic medical records systems such as Centricity, Amalga, and other patient 
charts such as the charts in the Division of Nuclear Medicine of MedStar Washington Hospital Center.  
Examples of data include the following:  
Demographics 
1. 
Age at diagnosis 
2. 
Gender 
 
Initial Diagnosis 
3. 
TNM at the time of diagnosis + AJCC thyroid cancer stage 
4. 
Histological type 
 
Initial Treatment 
5. 
Date of initial surgery  
6. 
Extent of initial surgery (total or subtotal) 
7. 
Histological subtype 
8. 
Post-operative Tg levels (suppressed and stimulated, when available) and thyroglobulin 
antibody 
9. 
Results of any other imaging studies including ultrasound, radioiodine scan, etc. 
10. Prescribed activity of any I-131 therapy 


11. Post I-131 therapy scan 
Six-month to one year follow-up results after initial treatment (patient history prior to sestamibi 
procedure) 
1. 
Follow up Tg levels (suppressed and stimulated, when available) 
2. 
Results of all other imaging studies including ultrasound, radioiodine scan, etc. 
Subsequent therapies 
3. 
Sequence and details of subsequent therapies. 
 
Additional information 
4. 
Number of prior I-131 therapies. 
5. 
Total cumulative prescribed activity (mCi) of I-131 received prior to the consideration of a 
“blind I-131 treatment.” 
6. 
Past imaging results (e.g. ultrasound, chest-x-ray, CT, MR, PET scan, etc.) 
7. 
Date, prescribed activity, and results of the most immediate prior I-131 therapy and post-
therapy scan.  
8. 
Results of dosimetry and dosimetric scan  
 
Performance of 99mTc Sestamibi Study. 
A. Procedure:  The following is the procedure for the 99mTc sestamibi study 
a. Intravenous injection of 20-30 mCi of 99mTc sestamibi 
b. Waiting period of approximately 1 hour 
c. Lying supine on a standard nuclear medicine gamma camera table for approximately 45 
minutes 
d. Use of parallel hole low energy collimator 
e. Acquisition time:  45 minutes 
f. Review of images by nuclear medicine physician for any extra views 
g. If necessary, either extra spot view, pinhole view, or SPECT (single photon emission 
computer tomography) image. 
h. Review of images by nuclear medicine physician. 
i. Release of patient.  
 
Radiation safety  
j. This study has been submitted to the Radiation Safety Committee 
k. Radiation Exposure:  Two routes 
i. From the 99mTc sestamibi: 
 


  
 
ii. From the low-dose localization CT of the SPECT. 
1. The PI submits that the decision by the nuclear medicine physician to 
perform an extra view, namely the SPECT-CT image, is arguably a clinical 
decision based on findings on the 99mTc sestamibi research scan.   Any 
finding on the research scan that is not initially interpreted as Grade 1 
(physiologic activity) or Grade 2 (probably physiologic activity) should be 
evaluated further based on the clinical indication to try to determine where 
this activity is precisely located in anticipation of potential treatment.   
 
However, the PI has included this in as part of the research study. 
Accordingly, there is additional radiation exposure from the low dose CT.  
The reason this is a low dose CT is because this CT is not a diagnostic CT 
but is only used for attenuation correction of the SPECT and localization of 
findings on the 99mTc sestamibi image.   When the CT is used for 
attenuation correction and localization, the exposure is significantly 
reduced from a diagnostic CT.  
 


For this study and to the estimate the percent additional radiation 
exposure to the volunteer, the data from Mhiri et al. has been used with 
the key table attached below [12] 
The percent increase of the effective dose by the inclusion of the CT is 
28%.  This is based on the 99mTc-MIBI parathyroid data above.  99mTc-MIBI 
is the abbreviation for 99mTc-sestamibi, and a CT used with 99mTc-MIBI for 
a parathyroid scan involves only one extra view.  In this case, when an 
SPECT-CT is requested by the interpreting physician for one of the 
subjects in this study, there is only one extra view.  Thus, 99mTc-MIBI 
parathyroid datum is a good surrogate for estimating the percent increase 
for a patient having a SPECT-CT in this study.  The only difference is 
instead of evaluating for possibly differentiated thyroid cancer, one is 
evaluating for parathyroid adenoma and that does not change the 
estimated increase in radiation dose.  
 
Side Effects of 99mTc sestamibi 
l. The prescribed information is attached in Appendix A. 
 
 
Contraindication of 99mTc sestamibi 
• None known per Prescribing Information. 
 
Exemption from a Sestamibi IND per 21 CFR 312.2(b) 
99mTc sestamibi is an approved FDA (Food and Drug Administration) radioisotope for the imaging of 


coronary artery disease (Cardiolite®) and breast lesions (Miraluma®). This study has no intentions to 
support a new indication or any other significant change in the labeling of the drug. There is no intention 
to support a change in the advertising for sestamibi. This study team has no intention to promote or 
commercialize sestamibi.     
The 99mTc sestamibi is commercially purchased from Cardinal Health or other available commercial 
entities that ensure labeling requirements are met. The study team does not utilize their own cyclotron to 
produce the sestamibi. The route of administration and activity (dose) of sestamibi are the same as that 
allowed in FDA indications. This study is under IRB review and patients provide signed informed 
consent prior to sestamibi scan.   
Exemption from a DSMB 
99mTc sestamibi is an approved FDA (Food and Drug Administration) radioisotope for the imaging of 
coronary artery disease (Cardiolite®) and breast lesions (Miraluma®).  Literally hundreds of thousands 
of doses have been administered, and the adverse effects are minimal and infrequent. As a result, the 
safety concerns are not unusually high and are very low.  Specifically and based on the Guidance for 
Clinical Trial Sponsors , Establishment and Operation of Clinical Trial Data Monitoring Committees, 
OMB Control No. 0910-5810, Expiration Date 12/31/2018,  there is no a priori reasons for a particular 
safety concern, no serious toxicity, no elevated risk of death/serious outcome, and the patient population 
is not fragile or vulnerable.  As a result, a DSMB not be required for this study. 
Data Safety Monitoring Plan 
 Close cooperation between the designated members of the Research Team will occur to 
evaluate and respond to individual adverse events in a timely manner.  Designated team 
members (Principal Investigator, Associate Investigators, and Study Coordinator,) will review 
the summary study safety data reports on a quarterly basis.  
I. Study Agent Accountability 
 
 Documentation  
The radiopharmacist/technologist will be responsible for maintaining an accurate record of the 
prescription number, inventory, and an accountability record of supplies for this study. 
Electronic documentation with dose manager as well as paper copies will be used.  
 Disposition  
The empty vials and the unused portion of a vial will be discarded according to the policies of 
the Radiation Safety Division of the Washington Hospital Center.   
 
II. Adverse Event Reporting 
 
a. 
Adverse Events 
An adverse event is any unfavorable or unintended change in body structure, body function or 
laboratory result associated temporally with the use of study treatment, whether or not 


considered related to the study treatment.    
b. 
Serious Adverse Events 
The term “Serious Adverse Drug Experience” is defined in 21 CFR 312.32 as follows:  “Any 
adverse drug experience occurring at any dose that results in any of the following outcomes:  
Death, a life-threatening adverse drug experience, inpatient hospitalization or prolongation of 
existing hospitalization, a persistent or significant disability/incapacity, or a congenital 
anomaly/birth defect.  Important medical events that may not result in death, be life-
threatening, or require hospitalization may be considered a serious adverse drug experience 
when, based upon appropriate medical judgment, they may jeopardize the subject or require 
medical or surgical intervention to prevent one of the outcomes listed in this definition.  
Examples of such medical events include allergic bronchospasm requiring intensive treatment 
in an emergency room or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalization, or the development of drug dependency or drug abuse.”  
 
c. 
Adverse Event Reporting  
Information on adverse events is collected by the principal investigator and other clinic staff 
and entered into a computer database.  These data are reviewed on an ongoing basis by the 
study coordinator and the principal investigator.  Adverse experiences that meet Serious 
Adverse Event (SAE) Reporting Requirements must be reported by the clinical site to the IRB.  
 
Briefly summarized, events requiring completion of an SAE report form include the following 
and these are to be reported regardless of assessed relationship to study agent:   
• Death  
• Permanent disability/incapacity  
• Hospitalization (other than for elective reasons and the planned I-131 treatment)  
• Grade 4 adverse events  
 
In addition, any event, regardless of grade, which in the judgment of a site investigator 
represents a serious adverse event, may be reported.  
 
For the purposes of this study, a Serious Adverse Event is defined as either (1) any Grade 3 or 
Grade 4 adverse untoward event as defined by the NCI criteria and/or (2) any event, which is 
considered in the opinion of the PI to be a serious adverse event.   The PI will report SAE’s 
within seven (7) days to the IRB.   
 
The patient will be tracked for SAE’s after the administration of the tracer prescribed activity of 
sestamibi up to the time of the patient’s release after completion of sestamibi scan.   The 
Serious Adverse Events form is attached (Appendix B). 
d. 
Adverse Event Reporting to the Institutional Review Board 
 
Adverse event reporting requirements to the MHRI Institutional Review Board (IRB) for this 


protocol are as follows:  
• Investigators will submit a completed serious adverse event report to the MRI IRB within 
7 days after becoming aware of a subject death, a potentially life-threatening (grade 4) 
serious adverse event that is possibly, probably or definitely related to investigational 
agent, an inpatient hospitalization (other than elective or the I-131 treatment), a 
persistent or significant disability/incapacity, or a congenital anomaly/birth defect.    
 
• Investigators will submit a completed serious adverse event report to the MHRI IRB 
within 15 days after becoming aware of any Grade 3 (severe) adverse event that is 
possibly, probably or definitely related to investigational agent.  
 
• Investigators will report within 15 days on any other event or condition regardless of 
grade, which in their judgment represents an event reportable to the IRB.    
 
• A summary of all adverse events will be reported to the MHRI IRB with submission of a 
request for continuing review. 
 
Interpretation of 99mTc Sestamibi Study. 
A. A team of two nuclear medicine physicians will interpret the 99mTc sestamibi, and any area of 
radioactivity will be graded as by a standard nuclear medicine grading system: 
1. Normal physiological activity 
2. Probably physiological activity 
3. Indeterminate activity 
4. Probably metastatic disease 
5. Metastatic disease 
B. Criteria for “final determination” regarding whether a finding represents physiological activity or 
metastatic disease:   
a. For findings graded as 1 or 2, they will be defined for this study as physiological activity. 
b. For findings graded as 3, or 4, the following will be required: 
i. Biopsy; however, this will only be performed if clinically indicated. 
1. Follow-up:  It is anticipated that very few biopsies will be performed and 
because the criteria for entering this study is NDCIS or NECIS,  the only 
alternative for confirming whether or not a foci of 99mTc sestamibi uptake 
on a scan is metastases will be follow up, which will be performed on a 
clinical bases depending on the patient’s treating physicians’ decisions.  
The study team will follow up through telephone at 1, 3, 6 and 12 months 
after the sestamibi scan and/or until diagnosis of the metastatic site.  The 
purpose of the telephone follow-up is to enquire on what, if any, blood 
tests, imaging studies or biopsies were ordered by the patient’s treating 
physician. However, if on follow up any of the following occur, then the 
focus will be categorized as a metastases (true positive).  
a. Subsequent biopsy, 


b. Subsequent clinical imaging study(s) (For example, although a lytic 
bone lesion in the area of interested was not present initially on the 
CT, a lytic lesion indicative of metastases may subsequently 
develop in that area, and for this study this will be defined  as 
evidence of metastases of DTC (true positive).   
 
ii. Blind I-131 treatment** with or without a prefatory scan:   If a “blind” I-131 
treatment” is clinically selected and the post I-131 therapy scan demonstrates 
uptake in the same areas as the 99mTc sestamibi, then the finding on the 99mTc 
sestamibi will be classified for this study as a metastases of DTC.  
  
c. Grade 5 is not anticipated, because unlike I-131, which can have patterns that are very 
specific for DTC, 99mTc sestamibi patterns are not specific for DTC.  
 
** A “blind I-131 treatment” is a potential therapeutic option, and this term means 
that the treating physician or team cannot identify the source of the patient’s 
elevated Tg, but because of factors such as the level of elevated Tg, the rate of 
rise of the Tg, and the patient’s clinical situation, a therapeutic administration of I-
131 is give despite being “blind” to the source of the Tg.   
Patient Numbers 
a.  As noted in the objective of this study, this is a pilot study.  As a pilot study, the present 
plan is to perform 15 patients.  If no findings of Grade 3, 4, or 5 are identified on the first 
fifteen 99mTc sestamibi scans, then the study will be terminated.   
b. If Grade 3, 4, or 5 findings are observed, then the study will continue with the follow-up 
of those patients with those findings to determine as best as reasonably possible 
whether or not the findings represent metastatic disease from DTC.  However, no 
further patients will be recruited for 99mTc sestamibi scanning until that data become 
available and reviewed.  
c. At this time, I am unable to establish what would be criteria to reinitiate 99mTc sestamibi 
scanning or completely terminate the study. 
Statistical analysis:   
1. I have initiated a conversation with Mihriye Mete regarding what additional statistical analysis 
may be reasonable for such a pilot study. 
PROJECT ORGANIZATION 
Organizational Flowchart 
 


 
• An authorization chart delegating various functions is being developed. 
Project timetable  
 
DATA HANDLING AND RECORD KEEPING 
Confidentiality 
 
The Principal Investigator will ensure that subjects’ anonymity is maintained. Subjects will not 
be identified in any reports on this study. All records will be kept confidential to the extent required by 
federal, state and local law.   
Study Documentation and Storage 
 
The Principal Investigator is responsible for maintaining a comprehensive and centralized filing 
system of all study-related (essential) documentation, suitable for inspection at any time by 
representatives from the MHRI, IRB, FDA, and/or applicable regulatory authorities.  
 
In addition, all original submission documentation will be maintained and be readily available at 
InfoEd. All essential documentation should be retained by the institution for the same period of time 
required for medical records retention. No study document should be destroyed without prior written 
agreement between the MHRI and the Principal Investigator. Should the investigator wish to assign 
the study records to another party or move them to another location, MHRI must be notified in writing 
of the new responsible person and/or the new location. 
 
All data will be coded, and the data and the code document will be on computer in a secure file 
with password on a secure computer with password. 
Problems/weaknesses:  The very nature of this study in regard to inclusion criteria, namely negative 
standard or extensive clinically diagnostic imaging scans, is problematic in determining “truth” 
regarding whether or not a foci of 99mTc sestamibi is secondary to metastatic DTC.  But that problem 
should not stop one from performing such a study evaluation for these problematic patients.  
• Oversee the entire study. 
Douglas Van Nostrand, MD
Principal Investigator
•Responsible for IRB Forms/ Submission
•Data collection
Di Wu, MD
Co-Investigator
• Responsible for IRB Forms/ Submission
• Data collection
Cristiane Gomes Lima, MD
Co-Investigator
August
Submit protocol to 
IRB
October
Obtain IRB approval 
and start gathering 
data
December
Preliminary partial 
data collection with 
submission of 
abstract
March 2017
Completion of 
data acquisition 
with subsequent 
analysis. 


Risk/Benefit Assessment:  The risk/benefit assessment for this study is very low.  The risk of side 
effects is typically <1%, and if they occur they are minor.   The likelihood of benefit is not known and 
is the objective of the study; however, if the source of the patient’s elevated serum thyroglobulin is 
identified, this could have significant potential benefit because of the potential for earlier treatment 
and avoidance of complications from the site of metastases later.    
Study Population-Gender/Ethnic Inclusion:  The selection of the study population is not based on 
gender or ethnicity.    
 
Data Management: As noted above, confidentiality will be maintained by coding each patient, and all 
of the patient's identifiers will be stored on the principal investigator’s computer in which the file and 
the computer are password protected.  
 
Subject Identification: All patients will be identified in the Division Nuclear Medicine at the MedStar 
Washington Hospital Center.   
 
Participation of Children:  Children of less than 18 years of age are not eligible to participate in this clinical 
trial.   
 
Compensation Plan for Subjects:  None 
 
Informed Consent:  Attached 
 
Vertebrate Animals: Not applicable 
 
Consultants—None 
 
Budget: 
 
 
The work will be performed by Douglas Van Nostrand (DVN) and Cristiane Lima (CL) and 
subsequently Di Wu (DW), future research assistant, who will be added to the study on arrival.   DVN 
works without salary or compensation and Cl’s and DW’s salary will be paid from the research fund 
for thyroid cancer research. 
 
 
For expenses related to abstract submission, poster presentation, travel for presentations, etc. 
will be paid from the research fund for nuclear medicine thyroid cancer. 
 
For the 99mTc Sestamibi radioisotope and scan, per Wayne Dunkle, the expense is $295.94 
for the 78801 scan code, which includes 99mTc tetrafosmin.   Because we will be using 99mTc 
sestamibi, there is an additional $10.00 surcharge.   
 
 
 
Item 
Charge 
Units 
Subtotal 
78801 scan 
$295.94 
15 
$4439.10 
Surcharge for 99mTc Sestamibi 
$10 
15 
$150.00 
Poster preparation, travel, lodging for 
$1900 
1 
$1900 


Presentation of initial results 
Poster preparation, travel, lodging for 
Presentation of final results 
$1900 
1 
$1900 
Manuscript preparation and submission 
including journal fees, etc.  
$1800 
1 
$1800 
Statistical analysis and support 
$1500 
1 
$1500 
Miscellaneous expenses 
 
 
$1200 
Cristiane Lima 
 
 
Salary already 
covered  
Di Wu 
 
 
Salary already 
covered  
D Van Nostrand 
 
 
Pro bono  
 
  
 
Appendices 
 
Appendix A:  Prescribing Information, which will be uploaded separately to InfoEd. 
 
Appendix B:  Adverse events form. 
 


 
 


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