Thyroid Therapy for Mild Thyroid Deficiency in Pregnancy (TSH)

The George Washington University Biostatistics Center

Status and phase: Completed; Phase 3

Conditions: Hypothyroxinemia; Subclinical Hypothyroidism; Pregnancy

Treatments: Drug: Levothyroxine; Drug: Placebo for Levothyroxine

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00388297

U10HD034116 (U.S. NIH Grant/Contract)

U10HD040544 (U.S. NIH Grant/Contract)

U10HD027860 (U.S. NIH Grant/Contract)

U10HD053118 (U.S. NIH Grant/Contract)

U10HD040545 (U.S. NIH Grant/Contract)

U10HD036801 (U.S. NIH Grant/Contract)

U10HD034136 (U.S. NIH Grant/Contract)

U10HD040500 (U.S. NIH Grant/Contract)

U10HD027915 (U.S. NIH Grant/Contract)

U10HD027917 (U.S. NIH Grant/Contract)

U10HD027869 (U.S. NIH Grant/Contract)

U10HD034208 (U.S. NIH Grant/Contract)

U10HD040560 (U.S. NIH Grant/Contract)

HD36801-TSH

U10HD040512 (U.S. NIH Grant/Contract)

U10HD040485 (U.S. NIH Grant/Contract)

U10HD021410 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1,203 patients

Sex: Female

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Triple Blind

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1,203 participants in 4 patient groups, including a placebo group

Levothyroxine for Subclinical Hypothyroidism

Experimental group

Description:

100 µg of Levothryoxine for participants with subclinical hypothyroidism

Treatment:

Drug: Levothyroxine

Placebo for Levothyroxine - Subclinincal Hypothyroidism

Placebo Comparator group

Description:

Placebo for Levothyroxine for participants with subclinical hypothyroidism

Treatment:

Drug: Placebo for Levothyroxine

Levothyroxine for Hypothyroxinemia - Hypothyroxinemia

Experimental group

Description:

50 µg of Levothyroxine for participants with hypothyroxinemia

Treatment:

Drug: Levothyroxine

Placebo for Levothyroxine

Placebo Comparator group

Description:

Placebo for Levothyroxine for participants with hypothyroxinemia

Treatment:

Drug: Placebo for Levothyroxine