Clinical trial NCT01832753: Treatment Trial of Subclinical Hypothyroidism in Down Syndrome
Official title: Levothyroxine Treatment and Cardiometabolic Outcomes in Adolescents With Down Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Down Syndrome
Subclinical Hypothyroidism
Keywords: Down syndrome
subclinical hypothyroidism
thyroid
levothyroxine
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2013-04-16
Enrollment: 12
Sex: ALL
Minimum age (years): 8
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this research study is to learn about the effects of treating subclinical hypothyroidism (SCH) with thyroid hormone replacement in children and adolescents with Down syndrome (DS). We hypothesize that treatment of SCH with thyroid hormone replacement will improve cardiometabolic health and quality of life.

Detailed description: The American Academy of Pediatrics (AAP) recommends yearly screening of thyroid studies in DS. Clinical experience suggests that thyroid stimulating hormone (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.

Eligibility criteria: Inclusion Criteria:

* Males and females, ages 8 - 20 years
* Diagnosis of Down syndrome
* Subclinical hypothyroidism: TSH level between 5 - 10 mIU/L, normal T4
* Parental/guardian permission (informed consent) and if appropriate, child assent
* Females who are at least 11 years of age or who are menarchal must have a negative urine/serum pregnancy test
* Committed to adherence to levothyroxine treatment and study completion

Exclusion Criteria:

* Pregnancy
* Type 1/Type 2 diabetes
* Chronic medical conditions or medication use that can affect growth, nutrition, blood glucose, insulin secretion, or thyroid function (such as lithium or certain seizure medications)
* Current use of levothyroxine or anti-thyroid hormone
* Cyanotic congenital heart disease, or pulmonary hypertension (as described by last echo report in subjects with CHD), or congenital heart disease considered medically unstable by the study cardiologists

Primary outcomes:
measure: Change in Lipid Panel From Baseline at 6, 12 and 18 Months.
timeFrame: baseline, 6 months, 12 months & 18 months
Secondary outcomes:
measure: Change in Quality of Life From Baseline at 6, 12 and 18 Months.
timeFrame: baseline, 6 months, 12 months, & 18 months
Other outcomes:
Locations:
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Andrea Kelly, MD, MSCE
role: PRINCIPAL_INVESTIGATOR
References: