Treatment Trial of Subclinical Hypothyroidism in Down Syndrome
Information source: Children's Hospital of Philadelphia
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Down Syndrome; Subclinical Hypothyroidism
Intervention: Levothyroxine (Drug)
Phase: N/A
Status: Recruiting
Sponsored by: Children's Hospital of Philadelphia Official(s) and/or principal investigator(s): Andrea Kelly, MD, MSCE, Principal Investigator, Affiliation: Children's Hospital of Philadelphia
Overall contact: Divya Prasad, MPH, Phone: 267-426-2778, Email: prasadd@email.chop.edu
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.
Clinical Details
Official title: Levothyroxine Treatment and Cardiometabolic Outcomes in Adolescents With Down Syndrome
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment
Primary outcome: Change in non-HDL cholesterol from baseline at 6, 12 and 18 months.
Secondary outcome: Change in quality of life from baseline at 6, 12 and 18 months.
Detailed description:
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.
Eligibility
Minimum age: 8 Years.
Maximum age: 20 Years.
Gender(s): Both.
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
Locations and Contacts
Divya Prasad, MPH, Phone: 267-426-2778, Email: prasadd@email.chop.edu
Children's National Medical Center, Washington, District of Columbia 20010, United States; Recruiting Sheela Magge, MD, MSCE, Phone: 888-884-2327 Sheela Magge, MD, MSCE, Principal Investigator
The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States; Recruiting Andrea Kelly, MD, MSCE, Phone: 215-590-3174, Email: kellya@email.chop.edu Andrea Kelly, MD, MSCE, Principal Investigator
Additional Information
Starting date: January 2013
Last updated: May 4, 2015
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