Clinical Trial: Selenium Supplementation in Pregnancy

Study Status: Recruiting
Recruit Status: Unknown status
Study Type: Interventional

Official Title: Selenium Supplementation Treatment in Euthyroid Pregnant Women With Autoimmune Thyroid Disease: Effects on Obstetrical Complications

Brief Summary:

Serum levels of isolated anti-thyroperoxidase (TPOab) and anti-thyreoglobulin (Tgab) autoantibodies are strongly associated with an increased risk of miscarriage and premature deliveries in euthyroid pregnant women. Replacement of thyroxine (LT4) or other supplementations in euthyroid-Ab positivity during pregnancy has not been established. The development of a safe and effective intervention that modulates inappropriate inflammatory responses could be a very important component of prevention against adverse health outcomes during pregnancy.

The anti-oxidant Selenium (Se) suppresses autoimmune destruction of thyrocytes and at daily dose of 200 mcg and 100 mcg decreases titers of serum TPOAb and TgAb also in Se-non-deficient patients with autoimmune thyroiditis (AIT).

The use of Se in AIT has been shown to reduce the incidence of postpartum thyroiditis and hypothyroidism.

Women with recurrent pregnancy loss had lower Se levels and Se deficiency has been implicated in the pathogenesis of AIT and in the impairment of T/B cell-mediated immunity.

The purpose of the present study is performed to establish the effect of Se supplementation in euthyroid women with AIT (pregnant and in whom embryo transfer is expected within 60 days) on Ab trend, thyroid function and structure, implantation rates, pregnancy rates, pregnancy outcome and number of obstetrical, fetal and neonatal complications.

Detailed Summary:

Adverse outcomes, postpartum thyroid dysfunction and permanent hypothyroidism have been associated with isolated TPOab positivity in euthyroid pregnant women.

In areas with severe selenium deficiency there is a higher incidence of thyroiditis due to a decreased activity of selenium-dependent glutathione peroxidase activity within thyroid cells. Selenium-dependent enzymes also have several modifying effects on the immune system. Therefore, even mild selenium deficiency may contribute to the development and maintenance of autoimmune thyroid diseases.

Selenium substitution exerts anti-inflammatory and anti-oxidant activities. Se could represents an important supplementation in euthyroid women with AIT in order to improve thyroid function and structure and to prevent obstetrical adverse events related to autoimmune diseases and reactive oxygen species, such as recurrent miscarriage and pre-eclampsia.

The aim of this study is to document the effects of Selenium Supplementation with and without L-thyroxine (LT4) in euthyroid women with AIT, during pregnancy.

This protocol will evaluate the trend of TPOab and Tgab, selenium concentration, thyroid volume and echogenicity, nodule formation and number of adverse effects that affect the mother (during and after pregnancy), the fetus, the infant and the heath service, needing to elucidate the nature of the emerging associations.

The study also aims to assess the impact of Selenium Supplementation on implantation rate and pregnancy rate in women with transfer planned within the next 60 days.

This is designed as a phase IV study on treatment with a cohort size of pregnant women and women in
Sponsor: University of Roma La Sapienza

Current Primary Outcome: Changes in TPOab and/or Tgab [ Time Frame: 0 and 14 ± 2, 24 ± 2, 32± 2, 36± 2 weeks; and between 3° and 6° month after labour; and optionally 12° after labour ]

Original Primary Outcome: Changes in TPOab and/or Tgab [ Time Frame: 0 and 12 ± 2, 20 ± 2, 32± 2, 36± 2 weeks; and 3 and 6 months after labour ]

Current Secondary Outcome:

• Changes in thyroid volume and echogenicity [ Time Frame: 0 and 14 ± 2, 24 ± 2, 32± 2, 36± 2 weeks; and between 3° and 6° month after labour; and optionally 12° after labour ]
  Also changes in thyroid nodules diameters and/or nodules formation will be measured by Ultrasonographic (US) imaging
• Changes in thyroid hormones (TSH, FT4, FT3) [ Time Frame: 0 and 14 ± 2, 24 ± 2, 32± 2, 36± 2 weeks; and between 3° and 6° month after labour; and optionally 12° after labour ]
• Evaluation of Maternal risks [ Time Frame: From the date of randomization until the date of first documented event ]
  Pre-eclampsia (gestational hypertension: systolic pressure ≥140 mmHg or diastolic blood pressure ≥ 90 mmHg [Korotkoff V] on ≥ 2 occasions after 20 weeks gestation), Miscarriage, Placental Abruption, Abruption, Gestational hypertension, Breech presentation at birth, Preterm birth (< 37 weeks gestation), Symptomatic hypothyroidism, Preterm labour, Postpartum haemorrhage, Postpartum depression, Postpartum Thyroiditis, Maternal death
• Evaluation of Infant risks [ Time Frame: From the date of labour until the date of the first documented event ]
  Small for gestational age, Admission to special care, Cretinism, Jaundice requiring phototherapy, Poor feeding, Constipation, Hoarse cry, Lethargy, Hypotonia, Macroglossia, Umbilical hernia
• Changes in of quality of life [ Time Frame: 0 and 14 ± 2, 24 ± 2, 32± 2, 36± 2 weeks; and between 3° and 6° month after labour; and optionally 12° after labour ]
  Quality of life will be measured by questionnaire SF12
• Evaluation of Health Services: [ Time Frame: from the date of admission until the date of discharge ]
  Maternal length of hospital stay (days), Neonatal length of hospital stay (in days), Cost of services
• Changes in the selenium-dependent antioxidant enzyme glutathione peroxidase [ Time Frame: 0, 24 ± 2, 36± 2 weeks; and 6 months after labour ]
  Glucose, Vitamin B-12, folate, methionine, albumin and cytokines will be also measured in serum
• Changes in implantation and pregnancy rates [ Time Frame: From the date of embryo transfer until the date of documented progression ]
  Clinical implantation rate (IR) and pregnancy rate (PR)

Original Secondary Outcome:

• Changes in thyroid volume and echogenicity [ Time Frame: 0 and 12 ± 2, 20 ± 2, 32± 2, 36± 2 weeks; and 3 and 6 months after labour ]
  Also changes in thyroid nodules diameters and/or nodules formation will be measured by Ultrasonographic (US) imaging
• Changes in thyroid hormones (TSH, FT4, FT3) [ Time Frame: 0 and 12 ± 2, 20 ± 2, 32± 2, 36± 2 weeks; and 3 and 6 months after labour ]
• Evaluation of Maternal risks [ Time Frame: before and after labour ]
  Pre-eclampsia (gestational hypertension: systolic pressure ≥140 mmHg or diastolic blood pressure ≥ 90 mmHg [Korotkoff V] on ≥ 2 occasions after 20 weeks gestation), Miascarriage, Placental Abruption, Abruption, Gestational hypertension, Breech presentation at birth, Preterm birth (< 37 weeks gestation), Symptomatic hypothyroidism, Preterm labour, Postpartum haemorrhage, Postpartum depression, Postpartum Thyroiditis, Maternal death
• Evaluation of Infant risks [ Time Frame: labour ]
  Small for gestational age, Admission to special care, Cretinism, Jaundice requiring phototherapy, Poor feeding, Constipation, Hoarse cry, Lethargy, Hypotonia, Macroglossia, Umbilical hernia, Patent fontanelles
• Changes in of quality of life [ Time Frame: 0 and 12 ± 2, 20 ± 2, 32± 2, 36± 2 weeks; and 3 and 6 months after labour ]
  Quality of life will be measured by questionnaire SF12
• Evaluation of Health Services: [ Time Frame: at labour ]
  Maternal length of hospital stay (days), Neonatal length of hospital stay (in days), Cost of services
• Changes in the selenium-dependent antioxidant enzyme glutathione peroxidase [ Time Frame: 0, 20 ± 2, 36± 2 weeks; and 6 months after labour ]
  Glucose, Vitamin B-12, folate, methionine, albumin and cytokines will be also measured in serum

Information By: University of Roma La Sapienza

Dates:
Date Received: November 2, 2011
Date Started: April 2012
Date Completion: May 2015
Last Updated: October 25, 2014
Last Verified: October 2014