Treatment Trial of Subclinical Hypothyroidism in Down Syndrome

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Children's Hospital of Philadelphia
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier:
NCT01832753
First received: April 9, 2013
Last updated: April 25, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention
Down Syndrome
Subclinical Hypothyroidism
Drug: Levothyroxine

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Children's Hospital of Philadelphia:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 40
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)
Arms Assigned Interventions
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.

Drug: Levothyroxine
Other Names:
  • Synthroid
  • Levothroid
  • Levoxyl
  • Tirosint
  • Unithroid
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.


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

Ages Eligible for Study:   8 Years to 20 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01832753

Contacts
Contact: Divya Prasad, MPH 267-426-2778 prasadd@email.chop.edu
Contact: Amber Lauff, BS 267-426-0299 lauffa@email.chop.edu

Locations
United States, Pennsylvania
The Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Principal Investigator: Andrea Kelly, MD, MSCE         
Principal Investigator: Sheela N. Magge, MD, MSCE         
Sponsors and Collaborators
Children's Hospital of Philadelphia
Investigators
Principal Investigator: Andrea Kelly, MD, MSCE Children's Hospital of Philadelphia
Principal Investigator: Sheela N. Magge, MD, MSCE Children's Hospital of Philadelphia
  More Information

No publications provided

Responsible Party: Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT01832753     History of Changes
Other Study ID Numbers: 12-009578, 1R01HD071981-01A1
Study First Received: April 9, 2013
Last Updated: April 25, 2014
Health Authority: United States: Institutional Review Board
United States: Data and Safety Monitoring Board

Keywords provided by Children's Hospital of Philadelphia:
Down syndrome
subclinical hypothyroidism
thyroid
levothyroxine

Additional relevant MeSH terms:
Syndrome
Down Syndrome
Hypothyroidism
Disease
Pathologic Processes
Thyroid Diseases
Endocrine System Diseases
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on September 18, 2014