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

History of Changes

Tracking Information

First Received Date ^ICMJE

October 12, 2006

Last Updated Date

September 9, 2016

Start Date ^ICMJE

October 2006

Primary Completion Date

August 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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 ]

Original Primary Outcome Measures ^ICMJE

Change History

Complete list of historical versions of study NCT00388297 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

Cognitive, Motor and Language Scale Scores from the Bayley Certified Scales of Infant Development III Edition [ Time Frame: 12 and 24 months of age ]
Cognitive and achievement levels from two DAS-II subtests (Recall of Digits Forward and Recognition of Pictures) [ Time Frame: 48 months of age ]
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 ]
Fetal growth [ Time Frame: Delivery ]
Preterm delivery [ Time Frame: Delivery ]
Preeclampsia [ Time Frame: Duration of pregnancy, Delivery ]
Abruption [ Time Frame: Duration of pregnancy, delivery ]
Stillbirth [ Time Frame: Delivery ]
Development of postpartum thyroid dysfunction [ Time Frame: 12 and 60 months postpartum ]
Cognitive and achievement levels from the Differential Ability Scales (DAS II) [ Time Frame: 36 months ]
Selected cognitive abilities from the subscales of the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) [ Time Frame: 60 months ]
Attention Deficit Hyperactivity Disorder (ADHD) index score from the Connors' Rating Scales (Parent-S) - Revised [ Time Frame: 48 months of age ]

Original Secondary Outcome Measures ^ICMJE

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

Current Other Outcome Measures ^ICMJE

Not Provided

Original Other Outcome Measures ^ICMJE

Not Provided

Descriptive Information

Brief Title ^ICMJE

Thyroid Therapy for Mild Thyroid Deficiency in Pregnancy

Official Title ^ICMJE

A Randomized Trial of Thyroxine Therapy for Subclinical Hypothyroidism or Hypothyroxinemia Diagnosed During Pregnancy

Brief Summary

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.

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.

Study Type ^ICMJE

Interventional

Study Phase

Phase 3

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double Blind (Participant, Care Provider, Investigator)
Primary Purpose: Treatment

Condition ^ICMJE

Subclinical Hypothyroidism
Hypothyroxinemia
Pregnancy

Intervention ^ICMJE

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

Study Arms

Experimental: Levothyroxine
Levothyroxine

Intervention: Drug: Levothyroxine
Placebo Comparator: Placebo for Levothyroxine
Placebo for Levothyroxine

Intervention: Drug: Placebo for Levothyroxine

Publications *

Casey BM, Thom EA, Peaceman AM, Varner MW, Sorokin Y, Hirtz DG, Reddy UM, Wapner RJ, Thorp JM Jr, Saade G, Tita AT, Rouse DJ, Sibai B, Iams JD, Mercer BM, Tolosa J, Caritis SN, VanDorsten JP; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal–Fetal Medicine Units Network. Treatment of Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy. N Engl J Med. 2017 Mar 2;376(9):815-825. doi: 10.1056/NEJMoa1606205.

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Completed

Enrollment ^ICMJE

1203

Completion Date

October 2015

Primary Completion Date

August 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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:

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 selective serotonin reuptake inhibitors (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

Sex/Gender

Sexes Eligible for Study:

Female

Ages

Child, Adult, Senior

Accepts Healthy Volunteers

Yes

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Listed Location Countries ^ICMJE

United States

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT00388297

Other Study ID Numbers ^ICMJE

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

Not Provided

IPD Sharing Statement

Plan to Share IPD:	Yes
Plan Description:	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.

Responsible Party

The George Washington University Biostatistics Center

Study Sponsor ^ICMJE

The George Washington University Biostatistics Center

Collaborators ^ICMJE

National Institute of Neurological Disorders and Stroke (NINDS)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators ^ICMJE

Principal Investigator:

Brian Casey, MD

University of Texas Southwestern Medical Center

PRS Account

The George Washington University Biostatistics Center

Verification Date

September 2016

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

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