Official Title: “A Randomized Trial of Thyroxine Therapy for Subclinical Hypothyroidism or Hypothyroxinemia Diagnosed During Pregnancy”

The purpose of this study is to determine whether treating women, who are diagnosed with a mild imbalance of thyroid hormones during pregnancy, with thyroid hormone replacement affects their children's intellectual development at 5 years of age.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: May 2014

Published research reports have stimulated national and international controversy regarding the value of maternal thyroxine therapy given to improve neurodevelopment of the fetus in women with variously defined hypothyroidism. These reports have led to conflicting and confusing recommendations as to whether or not all pregnant women in the U.S. should be screened for subclinical hypothyroidism or hypothyroxinemia.

Pregnant women less than 20 weeks gestation will have a blood test to screen for subclinical hypothyroidism or hypothyroxinemia. If eligible for the trial, patients will receive levothyroxine or placebo until delivery. Blood draws will be done at monthly study visits and the dosage will be adjusted based on test results. The children of these patients will have developmental testing done annually until they are 5 years of age.

Comparison(s): thyroxine supplementation versus placebo given during pregnancy to determine whether therapy is effective in improving intellectual ability at 5 years of age.

Intervention(s) in this Clinical Trial

• Drug: Levothyroxine
  • Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Primary Measures

• Intellectual function of children at 5 years of age, as measured by the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III), in women diagnosed with a) subclinical hypothyroidism or b) hypothyroxinemia during the first half of pregnancy

Secondary Measures

• Developmental delay at 12 and 24 months, using the Bayley Scales for Motor Development Index (MDI) and Psychomotor Development Index (PDI)
• Attention deficit at 48 months, using the Connors Rating Scales and the Developmental Neuropsychological Assessment (NEPSY) attention subtests
• Behavioral problems and social competencies at 36 and 60 months of age, as measured by the Child Behavior Checklist (CBCL)
• Fetal growth
• Preterm delivery
• Preeclampsia
• Abruption
• Stillbirth
• Development of postpartum thyroid dysfunction

Inclusion Criteria:

• Subclinical Hypothyroidism as defined by an elevated TSH (≥ 3.00 mU/L) and a free-T4 in the normal range (i.e. 0.86 to 1.90 ng/dL) or Hypothyroxinemia as defined by a TSH in the normal range (0.08 to 2.99 mU/L) and a low free-T4 (<0.86 ng/dL)
• Singleton Pregnancy
• Gestational age at randomization between 8 weeks 0 days and 20 weeks 6 days

Exclusion Criteria:

• 1. Major fetal anomaly or demise
• 2. Planned termination of the pregnancy
• 3. History of thyroid cancer or current thyroid disease requiring medication
• 4. Diabetes, on medication (insulin, glyburide)
• 5. Collagen vascular disease (autoimmune disease), such as lupus, scleroderma and polymyalgia rheumatica, on medication
• 6. Receiving anticoagulant therapy
• 7. Depression, currently on treatment with tricyclics or SSRIs
• 8. Other known serious maternal medical complications including:
• 1. Chronic hypertension requiring antihypertensive medication (including diuretics)
• 2. Epilepsy or other seizure disorder, on medication
• 3. Active or chronic liver disease (acute hepatitis, chronic active hepatitis) with persistently abnormal liver enzymes
• 4. Cancer (including melanoma but excluding other skin cancers)
• 5. Heart disease (tachyrhythmia, class II or greater heart disease or on heart medication). Mitral valve prolapse without arrhythmia is not an exclusion.
• 6. Asthma, on oral corticosteroids
• 9. Known illicit drug or alcohol abuse during current pregnancy
• 10. Delivery at a non-network hospital
• 11. Participation in another intervention study that influences maternal and fetal morbidity and mortality, or participation in this trial in a previous pregnancy
• 12. Unwilling or unable to commit to 5 year follow-up of the infant

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: National Institute of Child Health and Human Development (NICHD)

Overall Clinical Trial Officials and Contacts

Brian Casey, MD Principal Investigator University of Texas Southwestern Medical Center  

Overall Contact: Catherine Y Spong, MD 301-435-6894 spongc@exchange.nih.gov

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00388297

Study ID Number: HD36801-TSH

ClinicalTrials.gov Identifier: NCT00388297

Health Authority: United States: Institutional Review Board

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