Down SyndromeNCT01832753
Treatment Trial of Subclinical Hypothyroidism in Down Syndrome
A study testing Levothyroxine in people with Down Syndrome and Subclinical Hypothyroidism, run by Children's Hospital of Philadelphia at 2 sites in United States.
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). Read more about this study
- Who is it for?
- Ages 8 to 20 years
- Conditions the study is for
- Down Syndrome, Subclinical Hypothyroidism
- What is being tested?
- Levothyroxine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 2013to 18 Oct 2017
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 20 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
Official title: Levothyroxine Treatment and Cardiometabolic Outcomes in Adolescents With Down Syndrome
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.
Read the 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.
- Conditions
- Down Syndrome, Subclinical Hypothyroidism
- Being tested
- Levothyroxine
- Keywords
- Down syndrome, subclinical hypothyroidism, thyroid, levothyroxine
- Medical subject headings
- Down Syndrome, Thyroid Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevothyroxineDrug
Also called Synthroid, Levothroid, Levoxyl, Tirosint
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Lipid Panel From Baseline at 6, 12 and 18 Months.
Lipid panel will be measured via fasting blood draw.
Measured: baseline, 6 months, 12 months & 18 months
Secondary outcomes (1)
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.
Measured: baseline, 6 months, 12 months, & 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2013 (estimated)
- Study startJan 2013
- Primary completion18 Oct 2017
- Study completion18 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Down SyndromeStudies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Andrea Kelly, MD, MSCE, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01832753
- Sponsor's protocol ID
- 12-009578
- Other IDs
- 1R01HD071981-01A1
- Status last verified
- Sep 2019
- First submitted
- 9 Apr 2013
- Last updated
- 6 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Levothyroxine Treatment and Cardiometabolic Outcomes in Adolescents With Down Syndrome
- ClinicalTrials.gov ID
- NCT01832753
- Acronym / sponsor ID
- 12-009578
- Conditions
- Down Syndrome, Subclinical Hypothyroidism
- Keywords
- Down syndrome, subclinical hypothyroidism, thyroid, levothyroxine
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- Jan 2013 (actual)
- Primary completion
- 18 Oct 2017 (actual)
- Study completion
- 18 Oct 2017 (actual)
- First posted
- 16 Apr 2013 (estimated)
- Results
- Posted 13 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment Phase: Months 6-18 | Placebo comparator | Drug: LevothyroxineSubject 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. |
| 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. |
Who may qualify
- Ages
- 8 to 20 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LevothyroxineAlso: Synthroid, Levothroid, Levoxyl, Tirosint | Drug | Treatment Phase: Months 6-18 |
Primary outcome
Change in Lipid Panel From Baseline at 6, 12 and 18 Months.
Time frame: baseline, 6 months, 12 months & 18 months
Lipid panel will be measured via fasting blood draw.
1 secondary outcome
Change in Quality of Life From Baseline at 6, 12 and 18 Months.
Time frame: baseline, 6 months, 12 months, & 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrea Kelly, MD, MSCE principal investigator
Children's Hospital of Philadelphia
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Levothyroxine in people with Down Syndrome and Subclinical Hypothyroidism, run by Children's Hospital of Philadelphia at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Lipid Panel From Baseline at 6, 12 and 18 Months. (time frame: baseline, 6 months, 12 months & 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Sep 2019.