Thyroid Therapy for Mild Thyroid Deficiency in Pregnancy
Condition: Subclinical Hypothyroidism; Hypothyroxinemia; Pregnancy
MeSH terms: Hypothyroidism
Intervention: Levothyroxine; Placebo for Levothyroxine
Intervention description: 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.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 1203.0
Sex: Female
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Subclinical Hypothyroidism; Hypothyroxinemia; Thyroid; Pregnancy; Intellectual Development

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.
    

Eligibility 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 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