Thyroid Therapy for Mild Thyroid Deficiency in Pregnancy - Full Text View

Sponsor:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:	NCT00388297

Purpose

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.

Condition	Intervention	Phase
Subclinical Hypothyroidism Hypothyroxinemia Pregnancy	Drug: Levothyroxine	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Randomized Trial of Thyroxine Therapy for Subclinical Hypothyroidism or Hypothyroxinemia Diagnosed During Pregnancy

Resource links provided by NLM:

Drug Information available for: Thyroxine Levothyroxine Sodium Levothroid Thyroid

U.S. FDA Resources

Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome 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 [ Time Frame: 60 months of age ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Developmental delay at 12 and 24 months, using the Bayley Scales for Motor Development Index (MDI) and Psychomotor Development Index (PDI) [ Time Frame: 12 and 24 months of age ] [ Designated as safety issue: No ]
Attention deficit at 48 months, using the Connors Rating Scales and the Developmental Neuropsychological Assessment (NEPSY) attention subtests [ 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 ]

Enrollment:	1203
Study Start Date:	October 2006
Estimated Study Completion Date:	February 2015
Estimated Primary Completion Date:	May 2014 (Final data collection date for primary outcome measure)

Intervention Details:

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.

Detailed Description:

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.

Eligibility

Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

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:

Major fetal anomaly or demise
Planned termination of the pregnancy
History of thyroid cancer or current thyroid disease requiring medication
Diabetes, on medication (insulin, glyburide)
Collagen vascular disease (autoimmune disease), such as lupus, scleroderma and polymyalgia rheumatica, on medication
Receiving anticoagulant therapy
Depression, currently on treatment with tricyclics or SSRIs
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
Known illicit drug or alcohol abuse during current pregnancy
Delivery at a non-network hospital
Participation in another intervention study that influences maternal and fetal morbidity and mortality, or participation in this trial in a previous pregnancy
Unwilling or unable to commit to 5 year follow-up of the infant

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00388297

Locations

United States, Alabama
University of Alabama - Birmingham
Birmingham, Alabama, United States
United States, Illinois
Northwestern University
Chicago, Illinois, United States
United States, Michigan
Wayne State University
Detroit, Michigan, United States
United States, New York
Columbia University
New York, New York, United States
United States, North Carolina
University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States
United States, Ohio
Case Western University
Cleveland, Ohio, United States
Ohio State University
Columbus, Ohio, United States
United States, Oregon
Oregon Health & Sciences University
Portland, Oregon, United States
United States, Pennsylvania
University of Pittsburgh Magee Womens Hospital
Pittsburgh, Pennsylvania, United States
United States, Rhode Island
Brown University
Providence, Rhode Island, United States
United States, Texas
University of Texas - Southwest
Dallas, Texas, United States
University of Texas-Houston
Houston, Texas, United States
University of Texas Medical Branch - Galveston
Galveston, Texas, United States
United States, Utah
University of Utah Medical Center
Salt Lake City, Utah, United States

Sponsors and Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

Principal Investigator:

Brian Casey, MD

University of Texas Southwestern Medical Center

More Information

Additional Information:

Click here for more information about this study This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Pregnancy and Perinatology Branch, NICHD, NIH ( Catherine Y Spong, Chief )
Study ID Numbers:	HD36801-TSH, HD21410, HD27869, HD27917, HD27860, HD27915, HD34116, HD34208, HD34136, HD40500, HD40485, HD40544, HD40545, HD40560, HD40512, HD36801
Study First Received:	October 12, 2006
Last Updated:	December 16, 2009
ClinicalTrials.gov Identifier:	NCT00388297 History of Changes
Health Authority:	United States: Institutional Review Board; United States: Federal Government

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Subclinical Hypothyroidism
Hypothyroxinemia
Thyroid
Pregnancy
Intellectual Development

Additional relevant MeSH terms:

Endocrine System Diseases
Hypothyroidism
Thyroid Diseases

ClinicalTrials.gov processed this record on February 08, 2010