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Thyroid Therapy for Mild Thyroid Deficiency in Pregnancy (TSH)

This study has been completed.
Sponsor:
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
The George Washington University Biostatistics Center
ClinicalTrials.gov Identifier:
NCT00388297
First received: October 12, 2006
Last updated: September 9, 2016
Last verified: September 2016

October 12, 2006
September 9, 2016
October 2006
August 2015   (final data collection date for primary outcome measure)
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 [ Time Frame: 60 months of age ] [ Designated as safety issue: No ]
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
Complete list of historical versions of study NCT00388297 on ClinicalTrials.gov Archive Site
  • Cognitive, Motor and Language Scale Scores from the Bayley Certified Scales of Infant Development III Edition [ Time Frame: 12 and 24 months of age ] [ Designated as safety issue: No ]
  • Cognitive and achievement levels from two DAS-II subtests (Recall of Digits Forward and Recognition of Pictures) [ Time Frame: 48 months of age ] [ Designated as safety issue: No ]
  • Behavioral problems and social competencies at 36 and 60 months of age, as measured by the Child Behavior Checklist (CBCL) [ Time Frame: 36 and 60 months of age ] [ Designated as safety issue: No ]
  • Fetal growth [ Time Frame: Delivery ] [ Designated as safety issue: No ]
  • Preterm delivery [ Time Frame: Delivery ] [ Designated as safety issue: No ]
  • Preeclampsia [ Time Frame: Duration of pregnancy, Delivery ] [ Designated as safety issue: No ]
  • Abruption [ Time Frame: Duration of pregnancy, delivery ] [ Designated as safety issue: No ]
  • Stillbirth [ Time Frame: Delivery ] [ Designated as safety issue: No ]
  • Development of postpartum thyroid dysfunction [ Time Frame: 12 and 60 months postpartum ] [ Designated as safety issue: No ]
  • Cognitive and achievement levels from the Differential Ability Scales (DAS II) [ Time Frame: 36 months ] [ Designated as safety issue: No ]
  • Selected cognitive abilities from the subscales of the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) [ Time Frame: 60 months ] [ Designated as safety issue: No ]
  • Attention Deficit Hyperactivity Disorder (ADHD) index score from the Connors' Rating Scales (Parent-S) - Revised [ Time Frame: 48 months of age ] [ Designated as safety issue: No ]
  • 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
Not Provided
Not Provided
 
Thyroid Therapy for Mild Thyroid Deficiency in Pregnancy
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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
  • Subclinical Hypothyroidism
  • Hypothyroxinemia
  • Pregnancy
  • 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.
  • Drug: Placebo for Levothyroxine
  • Experimental: Levothyroxine
    Levothyroxine
    Intervention: Drug: Levothyroxine
  • Placebo Comparator: Placebo for Levothyroxine
    Placebo for Levothyroxine
    Intervention: Drug: Placebo for Levothyroxine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1203
October 2015
August 2015   (final data collection date for primary outcome measure)

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 micrometers (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 selective serotonin reuptake inhibitors (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
Female
Child, Adult, Senior
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00388297
HD36801-TSH, U10HD021410, U10HD027869, U10HD027917, U10HD027860, U10HD027915, U10HD034116, U10HD034208, U10HD034136, U10HD040500, U10HD040485, U10HD040544, U10HD040545, U10HD040560, U10HD040512, U10HD036801, U10HD053118
Yes
Yes
The data will be shared after the completion of the trial and publication of the main analyses per NIH policy. When made available, requests for the dataset(s) can be sent to mfmudatasets@bsc.gwu.edu.
The George Washington University Biostatistics Center
The George Washington University Biostatistics Center
  • National Institute of Neurological Disorders and Stroke (NINDS)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Principal Investigator: Brian Casey, MD University of Texas Southwestern Medical Center
The George Washington University Biostatistics Center
September 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP