Clinical trial NCT04747275
Conditions: Hypothyroidism Trisomy 21
Keywords: Tolerability Adherence
Sponsor: Children's Mercy Hospital Kansas City
Start date: 2021-01-18; Completion date: 2021-11-01
Enrollment: 6 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
Children with levothyroxine (T21) have developmental delay and other functional gastrointestinal (GI) issues that may negatively affect L-T4 tolerability and absorption. For an age group unable to swallow tablets whole by mouth, tablets must be crushed and suspended in water, breast milk or formula for administration in order to treat children with hypothyroidism. For this age group, ease of administration may have a significant impact on compliance and ability to remain euthyroid. We propose that Tirosint-SOL® will be more favorably received due to ease of administration, improved tolerability and palatability, therefore leading to improved adherence when compared to L-T4 tablets.

Detailed description:
Hypothyroidism is a common medical disorder in children with Trisomy 21 (T21). Treatment with oral tablet levothyroxine (L-T4) is primarily used to treat this condition. However, children with T21 have developmental delay and other functional gastrointestinal (GI) issues that may negatively affect L-T4 tolerability and absorption. For an age group unable to swallow tablets whole by mouth, tablets must be crushed and suspended in water, breast milk or formula for administration in order to treat children with hypothyroidism. For this age group, ease of administration may have a significant impact on compliance and ability to remain euthyroid. Until recently, there was no liquid preparation of L-T4 in the United States for use in children. Tirosint-SOL® (liquid stable L-T4) is now FDA-approved for use in children. The Investigator proposes that Tirosint-SOL® will be more favorably received due to ease of administration, improved tolerability and palatability, therefore leading to improved adherence when compared to L-T4 tablets.

Arms: arm 1: Participants start on Liquid Tirosint®-SOL for 8 weeks using continued same daily dose of LT4. Dose adjustments are allowed as needed, based on laboratory results and clinical response. Then Participants will crossover to conventional therapy of LT4 tablets for 8 weeks. Participants total participation will be 16 weeks total. arm 2: Participants continue conventional therapy of LT4 tablets for 8 weeks at current dose, after 8 weeks will crossover to receive Liquid Stable Levothyroxine (L-T4) Tirosint-SOL for 8 weeks. Participants total participation will be 16 weeks total.
Interventions: intervention 1: Liquid stable levothyroxine (L-T4) Tirosint-SOL intervention 2: Oral tablet levothyroxine (L-T4)
Intervention descriptions: intervention 1: Investigation of tolerability, palatability, and adherence of liquid levothyroxine (L-T4) for 8 weeks. intervention 2: Investigation of tolerability, palatability, and adherence of maintained oral tablet levothyroxine (L-T4) for 8 weeks

Protocol documents:
ICF_001.pdf: 
Tirosint®-SOL T21 Study – Parent/Child
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PARENTAL PERMISSION FOR CHILD TO PARTICIPATE IN A RESEARCH 
STUDY AT CHILDREN’S MERCY HOSPITALS
Tirosint®-SOL T21 Study
Use of Liquid Stable Levothyroxine in Trisomy 21 Pediatric Patients
SUMMARY (Details of this information are in the sections below)
We are asking your child to be in this research study. Being in a research study is completely voluntary, and your 
choice to participate or not participate will not affect your child’s regular medical care. This research study is being 
done to see if your child reacts differently to a liquid form of levothyroxine, called Tirosint®-SOL, compared to the 
levothyroxine pill used to treat hypothyroidism in children with Trisomy 21 and hypothyroidism. We will use a visual 
faces scale called the CareCAT tool to evaluate if your child prefers one form of medication more than the other and 
if your child is more likely to take the liquid versus the tablet.
The following things are parts of this study: your child will take either liquid Tirosint®-SOL or a levothyroxine pill for 8 
weeks. After 8 weeks of taking one of these medicines, your child will switch to taking the other for 8 weeks. The 
treatment forms your child starts on will be selected randomly like flipping a coin. You will answer survey questions, 
use a faces scale to tell us how well your child took the medicine, video your child taking the medication twice during 
the study, and keep track of the days your child took medicine. Your child’s medical chart will be reviewed, and we 
will measure your child’s height, weight, and head circumference. We will also collect 2 blood samples from your 
child during the study. Being in this study will include three visits to the Children’s Mercy Hospital Endocrine Clinic. 
Your child’s first visit can happen at the same time as your child’s regular clinic visit. Your child will be in this study 
for about 4 months.
The biggest risk from being in this study is that your child could absorb more of the liquid drug than they do the pill 
which could require your child’s doctor to change the dose of thyroid medication they are taking.
There may be no direct benefit of being in this study. Although, your child may benefit from being able to take their 
medication better based on the CareCAT survey tool. Your child may also have improved thyroid labs from more 
consistent dosing of medication. Being in this study, your child may help other children with Down Syndrome and 
hypothyroidism in the future.
There will be no cost to you or your child for being in this study. Instead of being in this study, your child can 
continue to get regular medical care.
WHO IS DOING THIS STUDY?
A study team led by Dr. Max Feldt is doing this study. Other health care professionals may help them.
IBSA Pharma is working with Children’s Mercy Hospital to do this research study. Funding for this study comes from 
the IBSA Pharma. The study team will not receive any personal payment because of your decision.
We are asking your child to be a part of this research study. Please read the information below and ask questions 
about anything that you do not understand before you make a choice.
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WHY IS THIS STUDY BEING DONE?
Hypothyroidism is a common disorder in children with Trisomy 21 (T21), also known as Down Syndrome. The 
purpose of this research study to see if the body reacts differently to a liquid form of levothyroxine called 
Tirosint®-SOL than it does the levothyroxine pill. We also want to know if you and your child like one more than 
the other and if your child is more likely to take the liquid drug versus the pill.
Tirosint-SOL® and Levothyroxine are both used as a replacement hormone that is normally produced by the thyroid. 
Both drugs are approved by the United States Food and Drug Administration (FDA) for the treatment of 
hypothyroidism in adults and children. There have been no studies testing the response of children with Down
Syndrome (T21) to Tirosint-SOL®. The study sponsor would like to learn if the liquid drug is more tolerable for 
children with Down Syndrome (T21).
WHO CAN BE IN THIS STUDY?
We are asking your child to be a part of this research study because he or she has been diagnosed with 
Trisomy 21 (T21) and hypothyroidism.
Up to 22 children, ages 2 months to less than 10 years will be in this study.
WHAT WILL HAPPEN TO MY CHILD IN THIS STUDY?
Before we do any study procedures, we will ask you to sign this permission form. A copy of the signed form will be 
given to you.
Being in this study involves three in-person visits (the first visit may happen virtually) and two phone calls, with some 
things you will do at home. 
The study details are below:
Enrollment Visit (Endocrine Clinic or Virtual):
Medical History: Your child’s medical history and use of medications and supplements will be reviewed and 
documented. You will also be asked about the use of non-prescription and herbal remedies. We will also review 
your child’s medical record.
Nutrition: If your child is 1 year or less, we will ask questions about whether your child is breast fed or formula fed. If 
your child is formula fed, we will ask if the formula includes soy or cow’s milk.
Demographic Data: Demographic data including your child’s age, race, and ethnicity will be obtained, as well as your 
home mailing address and email address.
Measurements: Your child’s height, weight, and head circumference will be collected from his/her most recent clinic 
visit.
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Lab tests: We will review and record lab results from your child’s most recent clinic visit.
Study Medicine: You will be given either Tirosint®-SOL liquid or levothyroxine pills to give to your child daily for the 
next 8 weeks. The dose that your child receives will be the same dose that your child’s doctor prescribes. Your child 
will need to take this medicine once a day for 8 weeks. We will know which medicine (liquid or tablet) your child will 
be on first after the first visit. Whether your child receives liquid or tablet first will be decided randomly like flipping a 
coin. There is an equal chance of your child being assigned to either group. You or your child’s doctor cannot decide 
which group your child will be assigned to. The study medicine will be mailed to your home after the doctor looks at 
your child’s lab results to make sure we give your child the correct dose of medicine. 
Medication Diary: You will be given a diary to record the day each dose of medicine is given to your child for the 
next 8 weeks.
PQL Survey: You will complete a Pediatric Quality of Life (PQL) survey, which tells us how taking medication affects you 
and your child. A link to the survey will be emailed to you for you to complete at home.
CareCAT Survey Tool: You will be trained how to complete an electronic survey which will be emailed to you each day 
for the 1st week your child starts taking the medication. The CareCAT Survey Tool is a simple faces scale that lets you 
answer how your child tolerates taking the medication. See example below.
CareCAT Example:
Week 1/Days 1-7 (At Home):
Study Medicine: You will give your child one dose, one time each day.
Video: When your child takes their first dose, you will video them taking that dose. You will email that video to the 
research team at tirostudy@cmh.edu, or you may be asked to upload this through an internet link that the study 
team emails you.
Medication Diary: You will record each day your child takes his/her medicine on a piece of paper provided by the 
study team.
CareCAT Survey: You will receive an email once a day for the first week your child is on the study medicine. This 
email will include a link to a survey that will include a faces scale called the CareCAT tool. You will indicate whether 
your child swallows the medicine well, refuses the medicine, spits up the medicine, vomits, or does not take the 
medicine using the provided tool. You may also complete this information by using a paper form provided by the 
study team if unable to do so online.
Phone Call: A member of the study team will contact you about 3 days after your child starts the medication to 
answer any questions you may have, to ensure you are able to send or upload the video and complete the 
survey.
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Week 2-8/Days 8-56 (At Home):
Study Medicine: You will give your child one dose, one time a day.
Medication Diary: You will record each day your child takes his/her medicine on a piece of paper provided by the 
study team.
Week 8/Day 56 +/- 4 days (Endocrine Clinic):
Medical History: Your child’s medical history and use of medications and supplements will be reviewed and 
documented. You will also be asked about the use of non-prescription and herbal remedies. 
Nutrition: If your child is 1 year or less, we will ask questions about whether your child is breast fed or formula fed. If 
your child is formula fed, we will ask if the formula includes soy or cow’s milk.
Measurements: Your child’s height, weight, and head circumference will be measured. Head circumference will only 
be measured if your child is less than 2 years old.
Study Medicine: We will collect any unused medication you have from the previous 8 weeks.   You may return the 
medication at this visit, or we will provide means for you to ship the medication to us.  You will be given the other 
form of medicine at this time. The dose that your child receives will be the same dose that your child’s doctor 
prescribes. Your child will need to take this medicine once a day for 8 weeks. The study medicine will be mailed to 
your home after the doctor looks at your child’s lab results to make sure we give your child the correct dose of 
medicine. 
Blood collection for lab tests: A blood sample of ½ a teaspoon will be collected from your child for thyroid lab tests 
(TSH & FT4) twice. A total of 1 teaspoon (5mL) will be collected during the study. Blood will be taken by needle stick 
from a vein in your child. Numbing cream will be used to help ease the pain of needle sticks. You will be given your 
child’s results of their thyroid labs (TSH & FT4) done for this research study.
Medication Diary: We will collect your first medication diary, and you will be given a new diary to record the day 
each dose of medicine is given to your child for the next 8 weeks.
PQL Survey: You will complete a Pediatric Quality of Life (PQL) survey, which tells us how taking medication affects you 
and your child. A link to the survey will be emailed to you for you to complete at home. You will also receive a paper 
form of this survey if you are unable to do so online.
CareCAT Survey: We will confirm your email and send a link for the CareCAT survey for you to start when your child 
starts the medication.
Week 9/Days 57-63 (At Home):
Study Medicine: You will give your child one dose, one time each day.
Video: When your child takes their first dose, you will video them taking that dose. You will email that video to the 
research team at tirostudy@cmh.edu, or you may be asked to upload this through an internet link that the study 
team emails you.
Medication Diary: You will record each day your child takes his/her medicine on a piece of paper provided by the 
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study team.
CareCAT Survey: You will receive an email once a day for the first week your child is on the study medicine. This 
email will include a link to a survey that will include a faces scale called the CareCAT tool. You will indicate whether 
your child swallows the medicine well, refuses the medicine, spits up the medicine, vomits, or does not take the 
medicine using the provided tool. You may also complete this information by using a paper form provided by the 
study team if unable to do so online.
Phone Call: A member of the study team will contact you about 3 days after your child starts the medication to 
answer any questions you may have, to ensure you are able to send or upload the video and complete the 
survey.
Weeks 10-16/Days 64-112 (At Home):
Study Medicine: You will give your child one dose, one time a day.
Medication Diary: You will record each day your child takes his/her medicine on a piece of paper provided by the study 
team.
Week 16/Day 112 +/- 4 days (Endocrine Clinic):
Medical History: Your child’s medical history and use of medications and supplements will be reviewed and 
documented. You will also be asked about the use of non-prescription and herbal remedies. 
Nutrition: If your child is 1 year or less, we will ask questions about whether your child is breast fed or formula fed. If 
your child is formula fed, we will ask if the formula includes soy or cow’s milk.
Measurements: Your child’s height, weight, and head circumference will be measured. Head circumference will only 
be measured if your child is less than 2 years old.
Medication Diary: We will collect the completed medication diary from you.
Study Medicine: We will collect any unused medication you have from the previous 8 weeks.   You may return the 
medication at this visit, or we will provide means for you to ship the medication to us. We will make sure your child 
has a new prescription for continuing his/her medicine at home. The study will no longer provide your child’s 
medication after this visit. 
Blood collection for lab tests: A blood sample of ½ a teaspoon will be collected from your child for thyroid lab tests 
(TSH & FT4) twice. A total of 1 teaspoon (5mL) will be collected during the study. Blood will be taken by needle stick 
from a vein in your child. Numbing cream will be used to help ease the pain of needle sticks. You will be given your 
child’s results of their thyroid labs (TSH & FT4) done for this research study.
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Table of Study Events: 
Procedures
Enrollment/Baseline
Visit 1
Dosing Week 1b
Days 1-7
Study Visit 2c
Day 3 +/-1 day
Dosing Weeks 2-8
Days 8-56
Study Visit 3, Week 8
Day 56 +/- 4 days
Dosing Week 9b
Days 63-70
Study Visit 4c
Day 65 +/-1 1 day
Dosing Weeks 10-16
Dyas 71-112
Study Visit 5
Day 112 +/- 4 days
Obtain permission/assent or consent
X
Demographics
X
Medical history
X
Randomization
X
Dispense study intervention
X
X
Concomitant medication review
X
X
X
X
X
Head Circumference
X
X
X
Height
X
X
X
Weight
X
X
X
Labs (TSH & FT4)
X
X
X
Adverse event review 
X
X
X
X
CareCAT Surveyd
X
X
Dosing Videoe
X
X
PQL Survey
X
X
Medication Administration Log
X
X
X
X
a: Head circumference, height, and weight and labs from enrollment/baseline visit will be collected from Standard of Care visit within the 
previous 6 weeks
b: Day 1 and Day 9 will be the first day of study drug administration in each arm
c: Study Visit 2 and Study Visit 4 will be phone calls
d: CareCAT survey will be done once daily during Week 1 and Week 9
e: Dosing videos to be done within first 5 days of dosing in each arm
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Optional Future Research Contact:
You will be asked whether we may contact you in the future about your child taking part in future research 
studies related to your child’s disease or condition. You will also be asked if data collected in this study can be 
used for future research. Your decision will not affect your child’s ability to be in this research study and will not 
affect your child’s routine care. You will be able to mark your choice at the end of this form.
WHAT ARE THE RISKS OF THE STUDY?
There are certain risks in this study. The biggest risk from being in this study is that your child could absorb more of 
the liquid medicine than they do the pill, which could require your child’s doctor to change the dose of thyroid 
medication they are taking.
The risks for levothyroxine and Tirosint®-SOL are the same and may include shortness of breath, irregular heart rate, 
heart attack, muscle spasms, headache, nervousness, irritability, insomnia, tremors, muscle weakness, increased 
appetite, weight loss, diarrhea, heat intolerance, and skins rash. Since your child will be on levothyroxine whether 
they are in this study or not, there is no increased risk from the medication due to study participation.
It is possible to have an allergic reaction to the other additional components included in either study drug. 
Allergic reactions usually happen right away after taking the medicine by mouth and symptoms include having a 
rash, swelling of the face or tongue, or vomiting. These reactions are very rare. If your child experiences a 
reaction, you should go to your nearest emergency room or call 911.
Risks of drawing blood from your child’s arm include discomfort and bruising. Your child will be given the option of 
numbing cream to help ease the pain of needle sticks. There is a very low risk of infection, bleeding, clotting, or 
fainting.
If your child has any of these problems or changes in the way he or she feels, you should tell the investigator or 
other study personnel as soon as possible.
There is a slight risk of loss of confidentiality. Your child’s confidentiality will be protected to the greatest extent 
possible. There also is a risk to confidentiality when using the internet. By providing your email or phone number, the 
study team may communicate with you regarding setting up appointments, sending copies of permission forms and 
any other non-clinical, study related communication using phone and email. 
Please be aware of the following:

Corresponding through electronic communication methods is not a secure method of sending information 
and others may be able to access the information sent.

The information may not be secure if storing or viewing the permission document on a personal electronic 
device (PED), especially if that PED is shared with other users or is lost, hacked, or subject to a search 
warrant or subpoena.

Information that is sent electronically may be kept on the Hospital's or your service provider's (Google, 
Yahoo, MSN, etc.) network servers. Unlike paper copies, e-copies delivered directly to your PED may not be 
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able to be permanently removed.

Children’s Mercy Hospital is not liable for any security breaches of any information sent electronically.
There may be risks we don’t know about right now. We will tell you about any new information that might change 
your decision to keep your child in the study.
WHAT ARE THE BENEFITS OF BEING IN THIS STUDY?
There may be direct benefit to your child being in this study, but your child may benefit from improved tolerability 
of absorption of their medication. Patients may also have an improved biochemical response to their medication 
seen with TSH & LT4 lab results. Being in this study, your child may help other children with Trisomy 21 and 
hypothyroidism in the future.
WHAT ABOUT EXTRA COSTS?
Both drugs will be provided to your child at no charge. You or your child’s insurer will be responsible for all other 
costs related to participation in this study. You will be responsible for any costs your child’s insurer does not cover. If 
you have any questions about these costs, or what out-of-pocket expenses you may be responsible for, contact your 
child’s insurer.
Some of the services or items in this study such as a clinic visit are also part of the regular treatment for your child’s 
condition. These services or items would be provided even if your child was not in this study. The costs for these 
services or items will be billed to your child’s insurer. You will be responsible for any such costs your child’s insurer 
does not cover. If your child is uninsured, you will be responsible for these costs. If you have any questions about 
these costs, or what out-of-pocket expenses you may be responsible for, contact a member of the study team.
Neither you nor your child’s insurer will be billed for the costs of any services or items that are required by the 
study but are not considered part of your child’s regular treatment.
WHAT ABOUT CONFIDENTIALITY?
Your child has rights regarding the privacy and confidentiality of his or her health information. When health 
information includes identifiers (like names, addresses, phone numbers and social security or individual 
taxpayer identification (ITIN) numbers) that link it directly to an individual, it is called protected health 
information (PHI). Federal laws require that PHI be kept secure and private. In certain situations, federal law 
also requires that you approve how your child’s PHI is used or disclosed. A research study is one of those 
situations.
By signing this permission form, you are permitting the following people to have access to your child’s medical record 
and use your child’s PHI for the research purposes described in this form. You are also permitting your child’s PHI to 
be shared with everyone listed below:

The research team, which includes persons involved in this study at Children’s Mercy Hospitals;

The IBSA Pharma and the people or groups hired to help perform this study;

The Institutional Review Board at Children’s Mercy Hospitals;

Other researchers, hospitals, and institutions that are part of this study and their Institutional Review Boards;

People from organizations that provide independent accreditation and oversight of hospitals and research;

Government/regulatory agencies (both US and international), such as the Office for Human 
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Research Protections whose job it is to protect human subjects and oversee the conduct of 
research.
The research record is separate from your child’s medical record. Information about your child that is obtained 
during this study will be recorded in a research record and may also be recorded in your child’s medical record. A 
research record will be created and kept in the Endocrine Research Office. The research record may include 
documents that have your child’s name, assigned study ID number, home street address, telephone number, 
medical record number, hospital account number, date of birth, dates of service, and email address. All research 
records will be maintained in a confidential manner.
Additionally, information to include your name, address, and date of birth will be collected from you for the purpose 
of compensating you for study participation. This information will remain on the Greenphire secure server 7 years 
after study closure and then will be destroyed. This information is needed for tax purposes related to compensation 
only.
There will be a separate database, in which all study information is collected. This database will be used to analyze 
the study information and find out the study results. Information in this database will include your child’s study ID 
number, name, initials, date of birth, and dates of service.
By signing this permission/assent form, you are allowing your child’s health information to be recorded in the 
research record. You are also permitting your child’s research record and medical record to be shared with everyone 
listed above.
Some people or groups who get your child’s identifiable health information might not have to follow the same 
privacy rules that we follow.  We will share your child’s health information only when we must, will only share the 
information that is needed, and will ask anyone who receives it from us to protect your child’s privacy. However, 
once your child’s information is shared outside of CMH we cannot promise that it will remain private.
You may choose not to sign this permission/assent form and not have your child be in the study. You may cancel your 
permission to use and share your child’s PHI at any time by contacting the study personnel listed on this form. You 
may also contact Children’s Mercy Hospitals Health Information Management (HIM) in writing. If you cancel your 
permission, your child may no longer participate in this study. Your child’s PHI that has already been collected for the 
study may still be used; however, no new information will be collected except information related to adverse events 
or other safety issues.
If you do not cancel your permission, your child’s PHI may continue to be recorded until the entire study is 
finished. This may take years. Any study information recorded in your child’s medical record will be kept forever. 
Unless stated elsewhere in this form, you may not have access to your child’s research record or research test 
results.
Results of this study may be made public. If made public, your child will not be identified in any publications or 
presentations.
In addition to the use of data described above, a description of this clinical trial will be available on 
http://www.ClinicalTrials.gov, as required by U.S. Law. This Web site will not include information that can identify 
your child. At most, the Web site will include a summary of the results. You can search this Web site at any time.
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WHAT ARE THE ALTERNATIVES TO BEING IN THIS STUDY?
Instead of being in this study, you may choose for your child not to be in the study.
WHAT WILL MY CHILD RECEIVE FOR BEING IN THIS STUDY?
You will receive up to $150 for completion of this study: $50 for Enrollment Visit, $50 for Week 8, $50 for Week 16. 
If your child does not complete the study, you will be compensated only for the visits that were completed. You will 
not be compensated for any unscheduled study visits.
If the total value of payments to you from Children’s Mercy Hospitals totals more than $600 in any calendar year, the 
hospital must report this to the IRS on a Form 1099 with the recipient’s social security number (SSN) or individual tax 
identification number (ITIN). You will receive a copy of this tax form. Accepting payment for taking part in the study 
may affect eligibility for Medicaid or other programs.
Children’s Mercy Hospitals can only make payment if we have your name, address, and date of birth. If you do not 
provide this information, your child can still participate in the research study; however, you will not receive 
payment.
WHAT ARE MY CHILD’S RIGHTS AS A STUDY PARTICIPANT?
Being in a research study is voluntary. Your child does not have to be in this study to receive medical care. If you 
choose for your child not to be in this study or withdraw you child from this study, there will be no penalty or loss 
of benefits to which your child is otherwise entitled.
We will inform you of any new information that we find out during this study. This information may affect your 
decision to keep your child in the study. If you choose to withdraw your child from (quit) the study or if you are 
asked by your child’s personal doctor to withdraw your child from the study, you must tell the study team as soon as 
possible.
If you withdraw your child from the study early for any reason, the information that already has been collected will 
be kept in the research study and included in the data analysis. If you withdraw, your child should continue their 
normal care with his or her Endocrinologist.
Dr. Feldt, IBSA Pharma the Institutional Review Board or the FDA may stop the study at any time. The 
investigator(s), your child’s doctor, or the IBSA Pharma may remove your child from the study at any time without 
your permission.
WHO SHOULD I CALL IF I HAVE QUESTIONS OR PROBLEMS?
Dr. Max Feldt oversees the conduct of this research study. If you have questions or concerns at any time during the 
study, you may call Dr. Feldt at (816) 960-8892. You may also contact the study coordinator, Darlene Brenson-
Hughes, by calling the Endocrine Research Central Phone at (816) 460-1097.
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You may page Dr. Feldt at 816-458-3697 if you believe that your child is sick or has suffered injury of any 
kind because of being in this research study.
You may also call Children’s Mercy Hospitals’ Pediatric Institutional Review Board (IRB) at (816) 731-7474 with 
questions or complaints about this study. The IRB is a committee of physicians, statisticians, researchers, community 
advocates, and others that ensures that a research study is ethical and that the rights of study participants are 
protected.
SPONSOR AND INSTITUTIONAL RESPONSIBILITIES
If your child has an illness or injury resulting from their participation in this study, notify the study doctor as soon as 
possible. If Children’s Mercy Hospitals provide treatment for this type of injury or illness, they will determine if they 
may bill insurance or other third-party payers for this care. You will be responsible for any treatment costs not 
covered by a third-party payer, but you may seek financial assistance from Children’s Mercy Hospitals.
PERMISSION OF PARENT OR LEGALLY AUTHORIZED REPRESENTATIVE
The purposes, procedures, and risks of this research study have been explained to me. I have had a chance to read 
this form and ask questions about the study. Any questions I had have been answered to my satisfaction. I give 
permission for 
to participate in this research study. A copy of this signed form will be 
given to me.
Optional Future Research Contact:
Please read each sentence below and think carefully about your choice. After reading each sentence, circle “Yes” 
or “No” and initial each item.
Someone from this Children’s Mercy Hospitals’ research team may contact me in the future to ask about my child 
participating in future research studies.
Yes
No
 
Initials of Parent/LAR
Making Your Choice for Optional Future Research:
Initials of Parent/LAR
No
Yes
Please read the sentence below and think carefully about your choice. After reading the sentence, circle “Yes” or 
“No” and initial.
I agree that my child’s clinical information can be used by other researchers for future pediatric research studies.
Signature of Parent/Legally Authorized Representative
Date
Relationship to Participant
IRB Effective Date: 4/4/2022


Tirosint®-SOL T21 Study – Parent/Child
IRB# STUDY00001385
Page 12 of 12
Version 8.0 17JAN2022
ASSENT OF MINOR
I have been told that if I am in this study, I will continue to take the thyroid medicine I normally take every day, or I 
will take a new liquid type of the medicine. I will have to come to Children’s Mercy for a blood draw and to check my 
height and weight two times during the 16-week study. My parent(s)/legal guardian(s) will answer questions about 
how well I like/take the medications and take a video of me taking my medication two times during the study. I have 
been told that I don’t have to be in this study. I may quit the study at any time, and no one will be mad at me. I have 
had a chance to discuss the study and ask questions. My questions have been answered. I agree to be in the study 
and do what I am asked to do, if I continue in the study.
I have read this form and/or had it read to me, and the research study has been explained to 
me. I have been given the chance to ask questions, and my questions have been answered.
I voluntarily agree to be in the research study described 
above. I will receive a copy of this consent form after I sign it.
I authorize the collection, use, and sharing of my personal health information and biological samples as 
described in this form.
I am not giving up any of my legal rights by signing this form.
Minor’s Name (Printed)
Signature of Minor
Date
STUDY PERSONNEL
I have explained the purposes, procedures, and risks involved in this study in detail to:
Print name(s) of Parents/ Legally Authorized Representative, and
 
, who in my opinion 
IS / 
IS NOT capable of assenting to participate in this study. 
Print child’s name.
If child IS NOT capable of assenting, please state reason why:
 
Age of child: 
(insert age)
 
Limitation in understanding based on child’s condition
 
Other, please explain  
Signature of Person Obtaining Permission/Assent
Date
Time
Print Name of Person Obtaining Permission/Assent:  
IRB Effective Date: 4/4/2022

Prot_002.pdf: 
SHORT TITLE: 
Tirosint®-SOL T21 Study 
 
 
 
 
STUDY00001385 
Page 1 of 13 
Version 10.0 22MAR2022 
 
PROTOCOL TITLE:  
Use of Liquid Stable Levothyroxine in Trisomy 21 Pediatric Patients 
PRINCIPAL INVESTIGATOR: 
M. Max Feldt, DO 
Pediatric Endocrinology 
816-960-8803 
mmfeldt@cmh.edu 
 
VERSION NUMBER/DATE: 
10.0 22MAR2022 
 
REVISION HISTORY 
 
Revision 
# 
Version Date 
Summary of Changes 
Consent 
Change? 
2 
19AUG2020 
Addition of AE/SAE Language 
No 
3 
23SEP2020 
Removing “vitals” from Summary of Events 
Table, this was an error 
Yes 
4 
12NOV2020 
Addition of Endocrine Clinic Intake Room and 
Outpatient Lab for Study Visits added. 
Addition of IRB approved recruitment flyers 
and Scope ad. 
Added recruitment at the Down Syndrome 
Clinic and associated Down Syndrome Support 
Group. 
Yes 
5 
29MAR2021 
Updated Sections 2.2, 11.0, and 12.0 to 
increase maximum age from less than 5 to less 
than 10 years. 
Updated Section 15.0 to increase study 
compensation to $50.00 per visit for a total of 
$150.00 for completion of all study visits. 
Corrected formatting in Section 28.00. 
Changed “Consent” to “Consent/Assent” in 
Summary of Events Table. 
Yes 
6 
17JUN2021 
Updated TOC to reflect correct page numbers, 
removed repetitive screening language, 
clarified that SOC visit labs must typically be 
within 6 weeks of baseline visit, clarified that 
head circumference should be obtained for 
Yes 


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Tirosint®-SOL T21 Study 
 
 
 
 
STUDY00001385 
Page 2 of 13 
Version 10.0 22MAR2022 
participants less than 2 years old, added that 
drug can be shipped or given to participants at 
CMH location, Recruitment at DS clinic 
described more clearly, changed protocol 
version and date. Updated Schedule of Events 
to reflect correct study visit days. 
7 
29OCT2021 
Reformatted protocol to match latest CM 
Research IRB version, and updated TOC to 
reflect changes; replaced Summary of Events 
table with Table of Events; redefined study 
drug vs control, inclusion/exclusion criteria,  & 
identification/pre-screening/recruitment of 
participants; more clearly explained and 
defined study procedures, including blood 
collection, & study surveys; added clarification 
to consent/assent process and assessment of 
participant’s ability to assent; updated 
withdrawal of participants language to allow 
study staff to withdraw due to study conduct 
concerns; clarified AE/SAE monitoring and 
investigator’s responsibilities; clarified 
statistical analysis, data and specimen 
management, and study setting/location; 
various changes in grammar and word usage 
to make language and content consistent 
throughout the protocol 
Yes 
8 
12NOV2021 
Typo in exclusion criteria: ≥ changed to ≤ 
No 
9 
13JAN2022 
PQL survey moved in Schedule of Events table 
in protocol and ICF 
Yes 
10 
22MAR2022 
Remove PQL survey from visit 3 schedule of 
events.  Reworded primary objective and 
other parts of protocol to remove the word 
compliance and changed to ease of use.   
yes 
 
 
 


SHORT TITLE: 
Tirosint®-SOL T21 Study 
 
 
 
 
STUDY00001385 
Page 3 of 13 
Version 10.0 22MAR2022 
Table of Contents 
STUDY INFORMATION 
1.0 Study Summary 
2.0 Objectives 
3.0 Background 
4.0 Study Endpoints 
5.0 Study Design 
6.0 Study Intervention/Investigational Agent 
PARTICIPANT MANAGEMENT 
7.0 Inclusion and Exclusion Criteria 
8.0 Local Number of Participants 
9.0 Screening and Recruitment Methods 
10.0 Procedures 
11.0 Surveys 
12.0 Sharing of Results with Participants 
13.0 Risks to Participants 
14.0 Potential Benefits 
15.0 Investigator Assessment of Risk/Benefits Ratio 
16.0 Payment, Reimbursement and Tangible Property Provided to Participants 
17.0 Economic Burden to Participants 
18.0 Permission/Assent/Consent Process 
19.0 HIPAA and Confidentiality 
20.0 Provisions to Protect the Privacy Interests of Participants 
21.0 Withdrawal of Participants 
DATA MANAGEMENT 
22.0 Data Collection 
23.0 Adverse Events and Unanticipated Problems 
24.0 Statistical Analysis 
25.0 Data and Specimen Management 
26.0 Settings and Locations 
 


SHORT TITLE: 
Tirosint®-SOL T21 Study 
 
 
 
 
STUDY00001385 
Page 4 of 13 
Version 10.0 22MAR2022 
STUDY INFORMATION 
1.0 
Study Summary 
1.1 Synopsis 
 
Study Title 
Use of Liquid Stable Levothyroxine in Trisomy 21 Pediatric 
Patients 
Study Design 
Single-center, pilot, randomized, open-label crossover study 
Primary Objective 
Assessment of and tolerability ease of use of levothyroxine 
therapy based on CareCAT validation tool and medication 
administration log 
Secondary Objective(s) Compare biochemical effect of liquid stable LT4 versus 
tablet LT4 on TSH and FT4 in T21 hypothyroid patients 
Research 
Intervention(s)/ 
Investigational 
Agent(s) 
Tirosint®-SOL liquid stable levothyroxine 
IND/IDE# 
N/A 
Study Population 
Pediatric patients with Trisomy 21 and hypothyroidism 
Sample Size 
22  
Study Duration for 
Individual Participants 
Approximately 4 months 
Study Specific 
Abbreviations/ 
Definitions  
CH – congenital hypothyroidism 
CMH – Children’s Mercy Hospital 
FT4 – Free thyroxine 
GI – gastrointestinal 
LT4 – levothyroxine 
SOC – standard of care 
TSH – thyroid stimulating hormone 
T21 – Trisomy 21 
 
2.0 
Objectives 
2.1 
Purpose, specific aims, or objectives:  Hypothyroidism is a common 
medical disorder in children with Trisomy 21 (T21).  Treatment with oral tablet 
levothyroxine (LT4) is primarily used to treat this condition. However, children 
with T21 have developmental delay and other functional gastrointestinal (GI) 
issues that may negatively affect LT4 tolerability and absorption. For an age 
group unable to swallow tablets whole by mouth, tablets must be crushed and 
suspended in water, breast milk or formula for administration to treat children 
with hypothyroidism.  For this age group, ease of administration may have a 
significant impact on compliance and ability to remain euthyroid.  Until recently, 
there was no liquid preparation of LT4 in the United States for use in children. 


SHORT TITLE: 
Tirosint®-SOL T21 Study 
 
 
 
 
STUDY00001385 
Page 5 of 13 
Version 10.0 22MAR2022 
Tirosint®-SOL (liquid stable LT4) is now FDA-approved for use in children. We 
propose that Tirosint®-SOL will be more favorably received due to ease of 
administration, improved tolerability, and palatability, therefore leading to 
improved adherence when compared to LT4 tablets. Our aims for this study are 
as follows: 
• Aim 1: Utilize medication tolerability questionnaire, CareCAT, to 
understand parental perceptions of liquid stable LT4 
• Aim 2: Evaluate differences in ease of use of liquid stable LT4 
compared to LT4 tablets 
• Aim 3: Compare biochemical effect of liquid stable LT4 versus 
table LT4 on TSH and FT4 in T21 hypothyroid patients 
2.2 
Hypothesis: We hypothesize that Tirosint®-SOL will be biochemically 
comparable to tablet LT4 as well as tolerated well and accepted by children with 
T21 and hypothyroidism ages 2 months to < 10 years.  Caregivers will perceive 
Tirosint®-SOL as a preferred dosage form. 
3.0 
Background 
3.1 
To date, there are no studies evaluating the response of liquid stable LT4 
in hypothyroid T21 children. 
3.2 
Trisomy 21 (T21) is one of the most common chromosomal disorders 
among live born infants. Its prevalence varies from 1 in 700 to 1 in 1500 live 
births. T21 is associated with many medical problems as well as developmental 
delay. Thyroid dysfunction is the most common endocrine abnormality and 
occurs in 4-8% of T21 children.  Hypothyroidism in T21 has a prevalence 
estimated to be 28-35 times higher than the general population.   Not all the 
mechanisms of hypothyroidism in T21 are known.  Autoimmune hypothyroidism 
is one common etiology as children with T21 have increased prevalence of 
autoimmunity.   Other possible etiologies include: 1. Exaggerated response to 
TRH stimulation in response to delayed maturation of hypothalamic – pituitary – 
thyroid axis; 2. Peripheral resistance to thyroid hormones (T4 and T3); 3. 
Reduced dopamine inhibition of TSH from altered dopaminergic regulation; and 
4. Reduced TSH bioactivity.  Due to these complex interactions, the use of 
traditional oral LT4 can lead to persistent elevation of TSH in 20-50% of 
hypothyroid T21 patients. The use of adjunctive liothyronine (L-T3) has been 
used to help normalize TSH but at the expense of complicating medication 
therapy.   Recently, a liquid stable formulation of LT4 has been FDA approved for 
children in the United States. This form has been approved, extensively studied, 
and utilized in Europe for many years. Tirosint®-SOL is packaged in mono-dose 
ampules in 12 different dosage strengths. Tirosint®-SOL may be administered 
either directly into the mouth or a spoon or diluted in a glass of water. This novel 
form of LT4 has advantages in pharmacokinetic profile compared to traditional 
tablet LT4 due to direct intestinal absorption without a dissolution phase.  


SHORT TITLE: 
Tirosint®-SOL T21 Study 
 
 
 
 
STUDY00001385 
Page 6 of 13 
Version 10.0 22MAR2022 
Traditional LT4 exists as a sodium salt that requires optimal acidic environment 
for dissolution and is susceptible to drug interference with calcium and iron 
supplements, estrogen, and other medications. On average approximately three 
quarters of the tablet LT4 is effectively absorbed.  In contrast, multiple studies 
have demonstrated liquid stable LT4 is less affected by concomitant medication 
and supplement administration, offers improved biochemical levels of TSH, FT4 
and FT3, and improved treatment compliance. 
4.0 
Study Endpoints 
4.1 
Primary endpoint: Parent perception responses from CareCAT medication 
tolerability tool 
4.2 
Secondary endpoint: TSH and FT4 drawn 8-weeks post intervention 
4.3 
Tertiary endpoint: linear growth (height), weight gain, and head 
circumference growth 
5.0 
Study Design 
5.1 
Study Design: This is a single-center, pilot, randomized, open-label, cross-
over study to determine satisfaction of standard LT4 tablets compared to liquid 
stable LT4 (Tirosint® -SOL) therapy and biochemical comparability in 22 
participants diagnosed with Trisomy 21 and congenital or acquired 
hypothyroidism already on levothyroxine (LT4). Participants will be randomized 
in a 1:1 ratio to treatment (Tirosint®-SOL) or control (conventional therapy with 
LT4 tablets) for 8 weeks, at which point they will then crossover to receive the 
treatment arm they were not initially randomized to receive.   
Participants will continue their same daily dose of LT4 or Tirosint®-SOL within the 
randomly assigned treatment group. Dose adjustments are allowed as needed, 
based on laboratory results and clinical response. Once enrolled, participants will 
be treated for 16 weeks total. The study will involve up to 3 in-person visits and 2 
safety phone calls. Enrollment visit may be done via approved CMH video 
conferencing platform.    
 
 
 
 
 
 
 
 
 


SHORT TITLE: 
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STUDY00001385 
Page 7 of 13 
Version 10.0 22MAR2022 
5.2 
Table of Events:  
Procedures 
Enrollment/Baselinea 
Visit 1 
Dosing Week 1b 
Days 1-7 
Study Visit 2c 
Day 3 +/-1 day 
Dosing Weeks 2-8 
Days 8-56 
Study Visit 3, Week 8 
Day 56 +/- 4 days 
Dosing Week 9b 
Days 63-70 
Study Visit 4c 
Day 65 +/-1 1 day 
Dosing Weeks 10-16 
Dyas 71-112 
Study Visit 5 
Day 112 +/- 4 days 
Obtain permission/assent or consent 
X 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
Randomization 
X 
 
 
 
 
 
 
 
 
Dispense study intervention 
X 
 
 
 
X 
 
 
 
 
Concomitant medication review 
X 
 
X 
 
X 
 
X 
 
X 
Head Circumference 
X 
 
 
 
X 
 
 
 
X 
Height 
X 
 
 
 
X 
 
 
 
X 
Weight 
X 
 
 
 
X 
 
 
 
X 
Labs (TSH & FT4) 
X 
 
 
 
X 
 
 
 
X 
Adverse event review  
 
 
X 
 
X 
 
X 
 
X 
CareCAT Surveyd 
 
X 
 
 
 
X 
 
 
 
Dosing Videoe 
 
X 
 
 
 
X 
 
 
 
PQL Survey 
X 
 
 
 
X 
 
 
 
 
Medication Administration Log 
 
X 
 
X 
 
X 
 
X 
 
a: Head circumference, height, and weight and labs from enrollment/baseline visit will be collected from Standard of Care visit within the 
previous 6 weeks 
b: Day 1 and Day 9 will be the first day of study drug administration in each arm 
c: Study Visit 2 and Study Visit 4 will be phone calls 
d: CareCAT survey will be done once daily during Week 1 and Week 9 
e: Dosing videos to be done within first 5 days of dosing in each arm 
 
6.0 
Study Intervention/Investigational Agent 
6.1 
Description: Tirosint®-SOL (levothyroxine sodium) is a ready-to-use clear, 
colorless to slightly yellow oral solution containing LT4. It is supplied in 1 mL 
white single-dose ampules. Inactive ingredients are glycerol and water. IBSA 
Pharma Inc. will provide Tirosint®-SOL for the study at the following strengths 
(mcg/mL): 13, 25, 38, 50. Commercially available LT4 tablets will also be used in 
the study. Inactive ingredients vary between formulations. LT4 tablets for the 
study will be supplied in the following strengths (mcg): 25, 50, 75.  Children’s 
Mercy IDS Pharmacy will store, handle, and dispense the study drug per 
Research Pharmacy SOP for the Control of Investigational Drugs. 
6.2 
Drugs or Biologics:  
Drug/Biologic Name 
FDA Approval Status and Use in this Study 
 Tirosint®-SOL 
 FDA approved, and being used within FDA labeling 
 Levothyroxine sodium 
 FDA approved, and being used within FDA labeling 


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Tirosint®-SOL T21 Study 
 
 
 
 
STUDY00001385 
Page 8 of 13 
Version 10.0 22MAR2022 
 
 
PARTICIPANT MANAGEMENT 
7.0 
Inclusion and Exclusion Criteria 
7.1 
Eligibility Criteria:  
Inclusion Criteria 
• Participant is at least 2 months old and less than 10 years of age  
• Prior confirmed diagnosis of Trisomy 21 
• Prior confirmed diagnosis of congenital or acquired hypothyroidism 
• Currently takes levothyroxine sodium by mouth 
• Gestational age >35 week 
Exclusion Criteria 
• Gestational age ≤35 weeks 
• Participant currently takes anticonvulsant medication 
• Participant takes medication through G-tube or another parenteral route 
• Participant has more than 2 missed SOC clinic visits in the last 2 years 
• Participant has documented history of noncompliance with levothyroxine 
• Participant is currently in foster care or state custody 
 
7.2 
Vulnerable Populations: Check any vulnerable populations that are being 
targeted for enrollment into the study: (Members of the following populations 
may not be included as participants in the research unless selected here.) 
☒ Children/Minors (under 7 years of age) 
☒ Children/Minors (7-17 years of age) 
☐ Neonates (infants less than 30 days old) 
☐ Neonates of Uncertain Viability (infants 
less than 30 days old) 
☐ Non-Viable Neonates (infants less than 
30 days old) 
☐ Wards of the State 
☐ Fetuses 
☐ Pregnant Women  
☐ Adults with impaired decision-making 
capacity         
☐ CM Employees 
☐ CM Students/Residents/ Fellows 
☐ Economically or Educationally 
Disadvantaged Persons 
☐ Prisoners 
 
 


SHORT TITLE: 
Tirosint®-SOL T21 Study 
 
 
Page 9 of 13 
 
• We will enroll children between the ages of 2 months and < 10 years, therefore 
meeting the definition of children as a vulnerable population. Participants may 
also have developmental delays. Study rationale, procedures, risks, and benefits 
will be explained prior to enrollment by one of the study team members using 
plain English with minimal medical terminology. The research staff will ensure 
that the potential participant’s parent(s)/LAR understand that participation is 
voluntary. Parent/LAR will be assured that their child’s research records will be 
kept confidential and will only be available to study personnel. To minimize 
coercion, parent(s)/LAR will be reassured that participation in no way influences 
or impacts their child’s medical treatment.  This research does not include other 
vulnerable populations including neonates, pregnant women, prisoners, or 
cognitively impaired adults. It is possible that a CMH employee’s child may be 
eligible for this study.  In this event, they will be allowed to participate.  The 
employee will be reassured that participation is voluntary.  If the research 
involves enrolling CM employees or students, indicate how the potential for 
employees/students to feel coerced or unduly influenced to participate will be 
minimized. For example, the risk of coercion may be minimized by ensuring that 
employees will not be recruited or enrolled by their direct supervisor. 
 
8.0 
Local Number of Participants 
8.1 
A total of 22 subjects will be enrolled in this study. Study participation 
will last approximately 4 months. 
 
9.0 
Identification and Recruitment of Potential Participants 
9.1 
Identification of Potential Participants: Patients may be identified from 
the CMH Endocrine Clinic outpatient visit schedule, by a list of potential eligible 
patients through a batch medical chart review from IT, individual chart review, or 
through outside referrals. Research staff may approach parent(s)/LAR of eligible 
patients during Endocrine Clinic visits, by phone, or by email.  Patients may also 
be referred by Downs Syndrome Clinic providers. Baseline visit may occur in 
Downs Syndrome Clinic with approval of Down Syndrome Clinic Medical 
Director. Potential participants may also self-refer in response to posted 
advertisements. Study team members may contact potential participants no 
more than three times to determine interest in this study.  Contact attempts and 
refusals will be documented in the pre-screening log. Refusals will not be 
approached further. 
9.2 
Pre-Screening prior to HIPAA Authorization: In accordance with 
45 CFR 164.512(i)(1)(ii), qualified participants will be identified and 
recorded initially by creation of a pre-screening log.  The pre-screening 
log will be maintained to aid in participant identification and eligibility 
status. This will aid key study personnel in efficiently and effectively 
attending clinic visits for optimal recruitment.  PHI may be collected and 
stored in pre-screening log and may contain, names (participant and 


SHORT TITLE: 
Tirosint®-SOL T21 Study 
 
 
Page 10 of 13 
 
parents/LAR), address, phone number, email address, medical record 
number, date of birth, age, clinic visit date, clinic location, clinic provider 
& appointment time, diagnoses, as well as coordinator/investigator notes 
regarding eligibility/scheduling. A Waiver of HIPAA is being requested for 
recruitment purposes only. Data from subjects who are determined 
ineligible or chose not to participate will be kept until the completion of 
enrollment to avoid approaching them multiple times.  When enrollment 
is complete, this data will be deleted for patients that did not enroll. 
9.3 
Recruitment of Potential Participants: IRB-approved recruitment 
flyers may be distributed at the CMH Endocrine and Down Syndrome 
Clinics and the Down Syndrome Guild of Greater Kansas City. The study 
may also be advertised using the recruitment flyer in the employee 
announcement bulletin board (Scope), internal employer website, or 
email.  
10.0 Procedures 
11.0 Surveys: 
12.0 Sharing of Results with Participants 
12.1 
Results of study labs will be provided to parents of subjects.  No other 
study data will be shared with subjects 
13.0 Risks to Participants 
13.1 
The risk for Levothyroxine and Tirosint®-SOL are the same and may 
include shortness of breath, irregular heart rate, heart attack, muscle spasms, 
headache, nervousness, irritability, insomnia, tremors, muscle weakness, 
increased appetite, weight loss, diarrhea, heat intolerance, and skins rash.  It is 
possible to have an allergic reaction to the other additional components included 
in either study drug. Allergic reactions usually happen right away after taking the 
medicine by mouth and symptoms include having a rash. These reactions are 
very rare. Participants will be on levothyroxine regardless of study participation, 
so there is no increased risk with study participation 


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Tirosint®-SOL T21 Study 
 
 
Page 11 of 13 
 
13.2 
The researchers believe the risks involved in this study are not greater 
than minimal risk 
14.0 Potential Benefits 
14.1 
Patients may benefit from improved tolerability of administration of the 
study drug. Subject may have improved biochemical response and absorption to 
medication, evaluated by TSH & LT4 lab results. 
16.0 Payment, Reimbursement and Tangible Property provided to 
participants 
17.0 Economic Burden to Participants 
18.0 Permission/Assent/Consent Process 
18.1 
Indicate below all methods of Permission/Consent that will be used in 
this study: 
18.2 
Assessment of Ability to Assent: Study staff will ask parent(s)/LAR if their 
child has been diagnosed with any developmental or cognitive delay. If yes, 
study staff will ask if parent(s)/LAR feel the participant is at or above the 
cognitive and development level of an average 7-year-old. Any child 7 years and 
older and at a cognitive or developmental level typical of an average 7-year-old 
will be assented. Study staff reserve the right to withhold assent on any 
participant deemed ineligible due to cognitive or development level based solely 
on the assessment of the study staff. Assessment of ability to assent will be 
documented in consent note per CMH research policy.  
18.3 
Permission/Assent/Consent Discussion: Consent and assent discussion 
may take place in one of the CMH Endocrine Clinic locations, by phone, or 
approved CMH video conferencing platform per CMH research policy. Consent 
discussions conducted in person will be held in a private room. Consent and 
assent will be presented by designated study staff to parent(s)/LAR. 
Parent(s)/LAR and participants will be reminded that research is voluntary and 
will be provided ample time to read, review, and ask questions about 
participating in the research study. Parent(s)/LAR and participant will be 
provided and allowed the opportunity to meet with the PI privately to discuss 
consent if requested. Parent(s)/LAR and participant will be provided a copy of 
the consent to take home to allow for more time if needed. Person giving 
consent and assent will utilize teach back to confirm understanding prior to 


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Tirosint®-SOL T21 Study 
 
 
Page 12 of 13 
 
signing of consent and assent. Parental consent and participant assent will be 
verbally confirmed prior to performing study procedures at every visit. 
19.0 HIPAA and Confidentiality 
19.1 
Full Written HIPAA Authorization will be obtained withing the 
permission/consent from. A Partial Waiver of HIPAA Authorization for 
Recruitment Only will be requested as described in section 9.2. 
19.2 
Research staff will emphasize that participate in research is voluntary and 
that participants may withdraw at any time without penalty. Verbal permission 
to continue participation in study will be obtained at the beginning of every 
study visit. All procedures will be explained with an opportunity for 
parent(s)/LAR to ask questions prior to proceeding with study procedures 
20.0 Provisions to Protect the Privacy Interests of Participants 
21.0 Withdrawal of Participants 
21.1 
Participants may be withdrawn by study staff at any time for an issue 
with study compliance, any concerns of harm to the participant, or if study labs 
reveal that the participant no longer needs levothyroxine (at the discretion of 
the PI). Participants may also be withdrawn if the study staff or CMH Research 
Compliance discover any issues that could compromise the safety of the 
participants or the integrity of the study data. Any participant withdrawals will 
be discussed with the PI and documented by the study coordinator in a research 
note in the electronic medical record. 
21.2 
All data collected prior to participant withdrawal will be retained by the 
study. Participants will be asked to return all study medication, both unused and 
empty packaging to the study coordinator to be returned to IDS Pharmacy for 
drug accountability. Participants will be instructed to continue their regular care 
with their Endocrine provider 
22.0 Data Collection 
23.0 Adverse Events and Unanticipated Problems 
23.1 
Monitoring: Parent(s)/LAR of participants will be asked at every study 
visit if there have been any changes to the participant’s health status since the 
last contact. Any change in medical history after enrollment visit will be 
considered an AE and will be documented. Any open AE/SAE at the end of study 
will only be followed if the PI has determined it is related to study participation. 


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Tirosint®-SOL T21 Study 
 
 
Page 13 of 13 
 
Open AE/SAEs attributed to study participation will be followed until resolved or 
the discretion of the PI. 
24.0 Statistical Analysis 
25.0 Data and Specimen Management 
26.0 Setting & Location 
26.1 
This study will be conducted at any of the CMH Endocrine Clinics or 
virtually through a CMH approved video conferencing platform. No community 
advisory boards will be involved in the research study. No study procedures will 
be conducted outside of the CMH organization. Participants will be given contact 
information for both the PI and lead Nurse Coordinator.  If laboratory results 
reflect a need in dose change, the child’s provider will be consulted for that 
decision.  No other anticipated medical or psychological resources are 
anticipated.