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Selenium Supplementation in Pregnancy

Information source: University of Roma La Sapienza
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Pregnancy; Infertility; Auto-immune Thyroiditis

Intervention: Selenium (Dietary Supplement); Sugar Pill Placebo (Other); Selenium + L-Thyroxine (LT4) (Other); Sugar Pill Placebo + L-Thyroxine (LT4) (Other)

Phase: Phase 4

Status: Recruiting

Sponsored by: University of Roma La Sapienza

Official(s) and/or principal investigator(s):
Andrea M Isidori, MD, PhD, Principal Investigator, Affiliation: Department of Experimental Medicine, Section of Clinical Pathophysiology and Endocrinology, "Sapienza" University of Rome

Overall contact:
Andrea M Isidori, MD, PhD, Phone: 0039-06-49970540, Email: andrea.isidori@uniroma1.it


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.

Clinical Details

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

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Primary outcome: Changes in TPOab and/or Tgab

Secondary outcome:

Changes in thyroid volume and echogenicity

Changes in thyroid hormones (TSH, FT4, FT3)

Evaluation of Maternal risks

Evaluation of Infant risks

Changes in of quality of life

Evaluation of Health Services:

Changes in the selenium-dependent antioxidant enzyme glutathione peroxidase

Changes in implantation and pregnancy rates

Detailed description: 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 whom embryo transfer is expected within 60 days with TSH value into the normal range (0. 4-2. 5 mUI/mL) and Tgab and/or TPOab positivity. We have performed two randomizations arms: Randomization arm A will include women LT4 replacement-free that will take Selenium or Placebo and Randomization arm B will include women already under LT4 replacement that will take Selenium or Placebo. Patients included in Randomization A will move into Randomization B, if TSH increases above 2. 5 mUI/mL during pregnancy. Pregnant women with TSH > 2. 5 mU/mL at time 0 will begin (or will adjust) LT4 replacement and will be included in Randomization arm B. Accounting for a 30% drop off, a total enrolment of 150 patients is planned. Patients will be randomized at time 0 (10°± 2 weeks of gestation). Follow-up visits will take place at weeks 14 ± 2, 24 ± 2, 32 ± 2, 36 ± 2 weeks, and between months 3° and 6° after labour. An optional visit could be done 12 months after labor. Plasma and serum monitoring of thyroid hormones, Tgab, TPOab, Se concentration, Selenoproteins and cytokines, thyroid US, SF12 questionnaire will be made at all the follow-up visits. At visit 3 (24 ± 2 weeks) patients will optionally do the OGTT). Gestational, obstetrical, maternal, fetal, and infant anamnestic data will be taken, during the follow up visits and at labour. The long-term objective is to identify a safe and easily administered supplementation that improves: 1. implantation and pregnancy rates in infertile women Tgab and/or TPOab positives 2. maternal and fetal complication in pregnant euthyroid women Tgab and/or TPOab positives.


Minimum age: 18 Years. Maximum age: 38 Years. Gender(s): Female.


Inclusion Criteria:

- pregnant women with 10°± 2 weeks of gestation

- women in whom embryo transfer is expected within 60 days

- euthyroid women (0. 4 μIU/ml < TSH < 2. 5 μIU/ml), positive for TPOab and/or TgAb, not

assuming LT4 replacement

- euthyroid women (0. 4 μIU/ml < TSH < 2. 5 μIU/ml), positive for TPOab and/or TgAb under

LT4 replacement (to maintain TSH within the control range).

- women with TSH > 2. 5 μIU/ml positive for TPOab and/or TgAb, not assuming LT4

replacement (requiring the beginning of LT4 replacement)

- women with TSH > 2. 5 μIU/ml positive for TPOab and/or TgAb, under LT4 replacement

(requiring an adjustment of LT4 replacement) Exclusion Criteria:

- use of dietary supplements containing selenium in the previous 4 months;

- use of antidepressive/psychotic drugs, amiodarone, propanolol, lithium, cytokines;

- history of hyperthyroidism positive anti-thyrotropin ab;

- previous partial or total thyroidectomy;

- known fetal anomaly;

- known infections (PID, HIV, HCV) and mola hydatidoses;

- chronic renal failure;

- uncontrolled hypertension;

- uterine malformation;

- history of medical and metabolic complication such as heart disease or diabetes;

- previous embryo transfer failed within last 3 months;

- miscarriage within last 3 months;

- gestational diabetes in previous pregnancies.

Locations and Contacts

Andrea M Isidori, MD, PhD, Phone: 0039-06-49970540, Email: andrea.isidori@uniroma1.it

Azienda ospedaliero-universitaria Careggi, Florence 50134, Italy; Active, not recruiting

Istituto Auxologico Italiano, Milan 20095, Italy; Active, not recruiting

Ospedale Maggiore Policlinico, Milan 20122, Italy; Recruiting
Giovanna Mantovani, MD, Email: giovanna.mantovani@unimi.it

University Federico II, Naples 80131, Italy; Recruiting
Anna Maria Colao, Prof, Email: annamaria.colao@unina.it

University "Piemonte Orientale, A. Avogadro", Novara 28100, Italy; Active, not recruiting

Department of Experimental Medicine, "Sapienza" University of Rome, Rome 00161, Italy; Not yet recruiting
Andrea M Isidori, MD, PhD, Phone: 0039-06-49970540, Email: andrea.isidori@uniroma1.it
Elisa Giannetta, MD, PhD, Phone: 0039-06-49970540, Email: elisa.giannetta@uniroma1.it

Department of Gynecological/Obstetric/Urological Sciences, "Sapienza" University of Rome, Rome 00161, Italy; Active, not recruiting

Dpt of Experimental Medicine, Rome 00161, Italy; Recruiting
Angela Fumarola, Prof., Email: angela.fumarola@uniroma1.it

European Hospital, Rome 00148, Italy; Active, not recruiting

Ospedale S. Giovanni Calibita Fatebenefratelli, Rome 00153, Italy; Active, not recruiting

Torvergata University of Rome - Ospedale S. Eugenio, Rome 00145, Italy; Active, not recruiting

Additional Information

Starting date: April 2012
Last updated: October 25, 2014

Page last updated: August 23, 2015

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