Use of Liquid Stable Levothyroxine in Trisomy 21 Pediatric Patients

Study Overview
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Brief Summary
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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
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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.

Official Title
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Use of Liquid Stable Levothyroxine in Trisomy 21 Pediatric Patients

Conditions
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Hypothyroidism, Trisomy 21

Intervention / Treatment
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* Drug: Liquid stable levothyroxine (L-T4) Tirosint-SOL
* Drug: Oral tablet levothyroxine (L-T4)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Trisomy 21 children age 2 months to less than 5 years of age Prior confirmed diagnosis of congenital or acquired hypothyroidism Exclusion Criteria: Gestational age ≤ 35 weeks, concomitant anticonvulsant medications, history of nonadherence with medication or medical visit schedule Subjects must be able to take oral medication, no G-tube or parental fed subjects

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 4 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Phase 4, single-center, pilot, randomized, open-label, cross-over study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Liquid Stable Levothyroxine (l-T4) TirosintSOL first, then Oral Tablet Levothyroxine (L-T4)<br>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. | Drug: Liquid stable levothyroxine (L-T4) Tirosint-SOL<br>* Investigation of tolerability, palatability, and adherence of liquid levothyroxine (L-T4) for 8 weeks.<br>Drug: Oral tablet levothyroxine (L-T4)<br>* Investigation of tolerability, palatability, and adherence of maintained oral tablet levothyroxine (L-T4) for 8 weeks<br>|
| Other: Oral Tablet Levothyroxine (L-T4) first, then Liquid Stable Levothyroxine (L-T4) Tirosint-SOL<br>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. | Drug: Liquid stable levothyroxine (L-T4) Tirosint-SOL<br>* Investigation of tolerability, palatability, and adherence of liquid levothyroxine (L-T4) for 8 weeks.<br>Drug: Oral tablet levothyroxine (L-T4)<br>* Investigation of tolerability, palatability, and adherence of maintained oral tablet levothyroxine (L-T4) for 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerability as Assessed by the CareCAT Tool | Utilize medication tolerability questionnaire, Care Children's Acceptance Tool (CAT), to understand parental perceptions of liquid stable L-T4. | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adherence to Taking Study Medication | Evaluate differences in compliance with liquid stable L-T4 compared to L-T4 tablet. Evaluated in percentage of days compliant. | 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tolerability, Adherence