Selenium Supplementation in Pregnancy

NCT ID: NCT01465867

Last Updated: 2018-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-30
• Study Completion Date: 2018-01-31

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 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.

Conditions

Pregnancy; Infertility; Auto-immune Thyroiditis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Selenium

Group Type: EXPERIMENTAL

Selenium

Intervention Type: DIETARY_SUPPLEMENT

83 micrograms of selenium (in the form of selenium methionine) in tablet form taken orally daily for all the length of pregnancy and for 3-6th month after labour

Sugar Pill Placebo

Group Type: PLACEBO_COMPARATOR

Sugar Pill Placebo

Intervention Type: OTHER

Placebo supplements in the same capsule as selenium. 1 tablet daily for all the length of pregnancy and for 3-6th month after labour.

Selenium + L-Thyroxine (LT4)

Group Type: EXPERIMENTAL

Selenium + L-Thyroxine (LT4)

Intervention Type: OTHER

83 micrograms of selenium (in the form of selenium methionine) in tablet form taken orally daily for all the length of pregnancy and for 3-6th month after labour

+ LT4 taken orally daily according to the dose required(in women already receiving it or needing of start it)

Sugar Pill Placebo + L-Thyroxine (LT4)

Group Type: EXPERIMENTAL

Sugar Pill Placebo + L-Thyroxine (LT4)

Intervention Type: OTHER

Placebo supplements in the same capsule as selenium. 1 tablet daily for all the length of pregnancy and for 3-6th month after labour

+ LT4 taken orally daily according to the dose required(in women already receiving it or needing of start it)

Interventions

Selenium

83 micrograms of selenium (in the form of selenium methionine) in tablet form taken orally daily for all the length of pregnancy and for 3-6th month after labour

Intervention Type: DIETARY_SUPPLEMENT

Sugar Pill Placebo

Placebo supplements in the same capsule as selenium. 1 tablet daily for all the length of pregnancy and for 3-6th month after labour.

Intervention Type: OTHER

Selenium + L-Thyroxine (LT4)

83 micrograms of selenium (in the form of selenium methionine) in tablet form taken orally daily for all the length of pregnancy and for 3-6th month after labour

+ LT4 taken orally daily according to the dose required(in women already receiving it or needing of start it)

Intervention Type: OTHER

Sugar Pill Placebo + L-Thyroxine (LT4)

Placebo supplements in the same capsule as selenium. 1 tablet daily for all the length of pregnancy and for 3-6th month after labour

+ LT4 taken orally daily according to the dose required(in women already receiving it or needing of start it)

Intervention Type: OTHER

Other Intervention Names

Intervention I (Se); Intervention II (Plb); Intervention III (Se+LT4); Intervention IV (Plb + LT4)

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 38 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of Roma La Sapienza

OTHER

Sponsor Role: lead

Responsible Party

Andrea M. Isidori

Principal Investigator, Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Andrea M Isidori, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Experimental Medicine, Section of Clinical Pathophysiology and Endocrinology, "Sapienza" University of Rome

Locations

Azienda ospedaliero-universitaria Careggi

Florence, , Italy

Istituto Auxologico Italiano

Milan, , Italy

Ospedale Maggiore Policlinico

Milan, , Italy

University Federico II

Naples, , Italy

University "Piemonte Orientale, A. Avogadro"

Novara, , Italy

Torvergata University of Rome - Ospedale S. Eugenio

Rome, , Italy

European Hospital

Rome, , Italy

Ospedale S. Giovanni Calibita Fatebenefratelli

Rome, , Italy

Department of Experimental Medicine, "Sapienza" University of Rome

Rome, , Italy

Department of Gynecological/Obstetric/Urological Sciences, "Sapienza" University of Rome

Rome, , Italy

Dpt of Experimental Medicine

Rome, , Italy

Countries

Italy

Other Identifiers

Sel-01

Identifier Type: -

Identifier Source: org_study_id