Thyroid Therapy for Mild Thyroid Deficiency in Pregnancy
TSH
A Randomized Trial of Thyroxine Therapy for Subclinical Hypothyroidism or Hypothyroxinemia Diagnosed During Pregnancy
17 other identifiers
interventional
1,203
1 country
14
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Oct 2006
Longer than P75 for phase_3
14 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
October 1, 2006
CompletedFirst Submitted
Initial submission to the registry
October 12, 2006
CompletedFirst Posted
Study publicly available on registry
October 16, 2006
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2015
CompletedResults Posted
Study results publicly available
January 30, 2019
CompletedFebruary 21, 2019
February 1, 2019
8.8 years
October 12, 2006
October 24, 2018
February 19, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Intellectual Function of Children at 5 Years of Age in Women Diagnosed With a) Subclinical Hypothyroidism or b) Hypothyroxinemia During the First Half of Pregnancy, or Death.
The primary outcome was death or IQ score at 5 years of age (or at 3 years of age if the 5-year examination was missing). The full-scale IQ was assessed with the use of the Wechsler Preschool and Primary Scale of Intelligence III (WPPSI-III) at 5 years of age or the overall (general conceptual ability) score from the Differential Ability Scales-II at 3 years of age if the WPPSI-III score was not available. Results are expressed as an age-standardized score, with an expected population mean of 100 and a standard deviation of 15. Death before 3 years of age was assigned a score of 0 (lowest possible rank) and was included in the estimation of the median. For Quotient and Composite score: below 70 is Extremely Low, 70-79 is Borderline, 80-89 is Low Average, 90-109 is Average, 110-119 is High Average, 120-129 is Superior, 130+
60 months of age
Secondary Outcomes (25)
Week of Gestation at Delivery
Delivery
Number of Participants With Preterm Delivery
Delivery
Selected Cognitive Abilities From the Subscales of the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III)
60 months
Cognitive and Achievement Levels From the Differential Ability Scales (DAS II)
36 months
Cognitive and Achievement Levels From Two DAS-II Subtests (Recall of Digits Forward and Recognition of Pictures)
48 months of age
- +20 more secondary outcomes
Study Arms (4)
Levothyroxine for Subclinical Hypothyroidism
EXPERIMENTAL100 µg of Levothryoxine for participants with subclinical hypothyroidism
Placebo for Levothyroxine - Subclinincal Hypothyroidism
PLACEBO COMPARATORPlacebo for Levothyroxine for participants with subclinical hypothyroidism
Levothyroxine for Hypothyroxinemia - Hypothyroxinemia
EXPERIMENTAL50 µg of Levothyroxine for participants with hypothyroxinemia
Placebo for Levothyroxine
PLACEBO COMPARATORPlacebo for Levothyroxine for participants with hypothyroxinemia
Interventions
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.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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:
- Chronic hypertension requiring antihypertensive medication (including diuretics)
- Epilepsy or other seizure disorder, on medication
- Active or chronic liver disease (acute hepatitis, chronic active hepatitis) with persistently abnormal liver enzymes
- Cancer (including melanoma but excluding other skin cancers)
- Asthma, on oral corticosteroids
- Known illicit drug or alcohol abuse during current pregnancy
- Delivery at a non-network hospital
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (14)
University of Alabama - Birmingham
Birmingham, Alabama, 35249, United States
Northwestern University
Chicago, Illinois, 60611, United States
Wayne State University
Detroit, Michigan, 48201, United States
Columbia University
New York, New York, 10032, United States
University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, 27599, United States
Case Western University
Cleveland, Ohio, 44109, United States
Ohio State University
Columbus, Ohio, 43210, United States
Oregon Health & Sciences University
Portland, Oregon, 97239, United States
University of Pittsburgh Magee Womens Hospital
Pittsburgh, Pennsylvania, 15213, United States
Brown University
Providence, Rhode Island, 02905, United States
University of Texas - Southwest
Dallas, Texas, 75235, United States
University of Texas Medical Branch - Galveston
Galveston, Texas, 77555, United States
University of Texas-Houston
Houston, Texas, 77030, United States
University of Utah Medical Center
Salt Lake City, Utah, 84132, United States
Related Publications (2)
Smid MC, Metz TD, McMillin GA, Mele L, Casey BM, Reddy UM, Wapner RJ, Thorp JM, Saade GR, Tita ATN, Miller ES, Rouse DJ, Sibai B, Costantine MM, Mercer BM, Caritis SN; for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network*. Prenatal Nicotine or Cannabis Exposure and Offspring Neurobehavioral Outcomes. Obstet Gynecol. 2022 Jan 1;139(1):21-30. doi: 10.1097/AOG.0000000000004632.
PMID: 34856574DERIVEDCasey 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.
PMID: 28249134DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Elizabeth Thom, Ph.D.
- Organization
- The George Washington University Biostatistics Center
Study Officials
- STUDY CHAIR
Brian Casey, MD
University of Texas Southwestern Medical Center
- STUDY DIRECTOR
Menachem Miodovnik, MD
NICHD Project Scientist
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 12, 2006
First Posted
October 16, 2006
Study Start
October 1, 2006
Primary Completion
August 1, 2015
Study Completion
October 1, 2015
Last Updated
February 21, 2019
Results First Posted
January 30, 2019
Record last verified: 2019-02
Data Sharing
- IPD Sharing
- Will share
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.