Treatment Trial of Subclinical Hypothyroidism in Down Syndrome
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
|Official Title:||Levothyroxine Treatment and Cardiometabolic Outcomes in Adolescents With Down Syndrome|
- Change in non-HDL cholesterol from baseline at 6, 12 and 18 months. [ Time Frame: baseline, 6 months, 12 months & 18 months ] [ Designated as safety issue: No ]Lipid panel will be measured via fasting blood draw.
- Change in quality of life from baseline at 6, 12 and 18 months. [ Time Frame: baseline, 6 months, 12 months, & 18 months ] [ Designated as safety issue: No ]Questionnaires will be done with participants and parents on the day of each study visit to determine body image and quality of life.
|Study Start Date:||January 2013|
|Estimated Study Completion Date:||May 2017|
|Estimated Primary Completion Date:||May 2017 (Final data collection date for primary outcome measure)|
Placebo Comparator: Treatment Phase: Months 6-18
Subject who are found to have SCH at the 6-month visit will be randomized to receive either levothyroxine or placebo during months 6-12. Levothyroxine dose will be between 0.5 - 1 mcg/kg/day. There will be 1 blood draw visit at month 7.5 (6 weeks after randomization) and 1 study visit at month 12 that will provide the opportunity for dose adjustments if needed.
From months 12-18, all subjects will receive levothyroxine. Levothyroxine dose will be between 0.5 - 1 mcg/kg/day. There will be one blood draw visit at month 13.5 that will provide the opportunity for dose adjustments if needed.
No Intervention: Observation Phase: Months 0-6
Subjects will be observed for the first 6 months of the study to ensure that the subclinical hypothyroidism is persistent. Subjects who do not have SCH at 6 months will not proceed to the treatment phase.
Subjects that have TSH >10 mIU/L during the 6 month Observational Phase will not be considered subclinical and will not qualify to continue the study. They will be referred to an endocrinologist for treatment.
The American Academy of Pediatrics (AAP) recommends yearly screening of thyroid studies in DS. Clinical experience suggests that TSH concentrations in the subclinical hypothyroid range (5-10 milli international units(mIU/L)) are not uncommon in DS, but the benefits and risks of treating SCH in the DS population are not known. In adults, SCH has been associated with increased cardiometabolic risk (CMR) and individuals with DS may be at increased cardiometabolic risk as well.
Data in children with SCH are limited. Despite the recommendations to screen for thyroid dysfunction, evidence to guide management of elevated TSH in children with DS is equally sparse. In non-DS children, TSH>4.65 mIU/L was associated with lower HDL. One year of levothyroxine treatment in short children with subclinical hypothyroidism and short stature improved growth velocity. Left ventricular (LV) function and LV mass (by echocardiography) was not different in 16 children with DS and subclinical hypothyroidism (TSH>6.5 mIU/L; mean TSH = 7.8 mIU/L) vs. 25 children with DS and normal TSH. However, these findings may be limited by the small sample size. An intervention study of 7 subjects age 2-42 years with DS and hypothyroidism, defined as low T4 and normal or elevated TSH (0.2-18.9 mIU/L) on 8 weeks of levothyroxine treatment did not improve developmental or functional outcomes. Anthropometrics and CMR factors were not examined. In contrast, increased TSH in the absence of overt congenital hypothyroidism is common in neonates with DS and prompted a randomized controlled trial (RCT) in 181 neonates with DS. TSH-directed levothyroxine treatment was associated with better growth, weight gain, and motor development after 24 months compared to placebo. These findings highlight that the "asymptomatic" component of subclinical hypothyroidism may have medically-relevant effects. This study will provide potentially clinically relevant preliminary evidence for the treatment of subclinical hypothyroidism in DS.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01832753
|Contact: Divya Prasad, MPHfirstname.lastname@example.org|
|Contact: Amber Lauff, BSemail@example.com|
|United States, District of Columbia|
|Children's National Medical Center||Recruiting|
|Washington, District of Columbia, United States, 20010|
|Contact: Sheela Magge, MD, MSCE 888-884-2327|
|Principal Investigator: Sheela Magge, MD, MSCE|
|United States, Pennsylvania|
|The Children's Hospital of Philadelphia||Recruiting|
|Philadelphia, Pennsylvania, United States, 19104|
|Contact: Andrea Kelly, MD, MSCE 215-590-3174 firstname.lastname@example.org|
|Principal Investigator: Andrea Kelly, MD, MSCE|
|Principal Investigator:||Andrea Kelly, MD, MSCE||Children's Hospital of Philadelphia|