Treatment Trial of Subclinical Hypothyroidism in Down Syndrome

Down Syndrome Clinical Trial

Official title:

Levothyroxine Treatment and Cardiometabolic Outcomes in Adolescents With Down Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01832753
• Other study ID #: 12-009578
• Secondary ID: 1R01HD071981-01A
• Status: Completed
• Phase: N/A
• Start date: January 2013
• Est. completion date: October 18, 2017

Study information

• Verified date: September 2019
• Source: Children's Hospital of Philadelphia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: October 18, 2017
• Est. primary completion date: October 18, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years to 20 Years

Eligibility

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

Related Conditions & MeSH terms

• Down Syndrome
• Hypothyroidism
• Subclinical Hypothyroidism
• Syndrome

Intervention

Drug:
• Levothyroxine

Locations

Country	Name	City	State
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Children's Hospital of Philadelphia	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Lipid Panel From Baseline at 6, 12 and 18 Months.	Lipid panel will be measured via fasting blood draw.	baseline, 6 months, 12 months & 18 months
Secondary	Change in Quality of Life From Baseline at 6, 12 and 18 Months.	Questionnaires will be done with participants and parents on the day of each study visit to determine body image and quality of life. The Pediatric Quality of Life (PedsQL) scale is a 5-item scale (values 1-5). 1 - "Always True", to 5 - "Never True". Items are reverse-scored and linearly transformed to a 0-100 scale (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0), so that greater scores indicate better QOL.	baseline, 6 months, 12 months, & 18 months