Use of Liquid Stable Levothyroxine in Trisomy 21 Pediatric Patients

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.

Study Overview

• Status: Terminated
• Conditions: Hypothyroidism; Trisomy 21
• Intervention / Treatment: Drug: Liquid stable levothyroxine (L-T4) Tirosint-SOL; Drug: Oral tablet levothyroxine (L-T4)

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months to 4 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Children's Mercy Hospital Kansas City

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2021
• Primary Completion (Actual): November 1, 2021
• Study Completion (Actual): November 1, 2021

Study Registration Dates

• First Submitted: February 3, 2021
• First Submitted That Met QC Criteria: February 8, 2021
• First Posted (Actual): February 10, 2021

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 11, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Adherence; Tolerability
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Endocrine System Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Thyroid Diseases; Intellectual Disability; Abnormalities, Multiple; Chromosome Disorders; Chromosome Aberrations; Aneuploidy; Chromosome Duplication; Hypothyroidism; Down Syndrome; Trisomy
• Other Study ID Numbers: STUDY00001385

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No