Treatment Trial of Subclinical Hypothyroidism in Down Syndrome

NCT01832753 | Completed Results DMC

• 2 other identifiers: 12-0095781R01HD071981-01A1
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

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.

Conditions

Down Syndrome; Subclinical Hypothyroidism

Keywords

Down syndrome; subclinical hypothyroidism; thyroid; levothyroxine

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Change in Quality of Life From Baseline at 6, 12 and 18 Months.

  baseline, 6 months, 12 months, & 18 months

Study Arms (2)

Treatment Phase: Months 6-18

PLACEBO COMPARATOR

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

Observation Phase: Months 0-6

NO INTERVENTION

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.

Interventions

Levothyroxine DRUG

Also known as: Synthroid, Levothroid, Levoxyl, Tirosint, Unithroid

Treatment Phase: Months 6-18

Eligibility Criteria

• Age: 8 Years - 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (2)

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Down Syndrome; Thyroid Diseases

Interventions

Thyroxine

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thyroid Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Limitations and Caveats

This was a pilot and feasibility study. The number of children with Down syndrome who had elevated TSH (5-10 IU/mL) and who were not on thyroid hormone replacement limited our ability to recruit.

Results Point of Contact

• Title: Andrea Kelly, MD MSCE
• Organization: The Children's Hospital of Philadelphia

kellya@email.chop.edu

215-590-3174

Study Officials

• Andrea Kelly, MD, MSCE

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2013
• First Posted: April 16, 2013
• Study Start: January 1, 2013
• Primary Completion: October 18, 2017
• Study Completion: October 18, 2017
• Last Updated: September 6, 2019
• Results First Posted: June 13, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)