Selenium Supplementation in Pregnancy

NCT01465867 | Completed DMC

• 1 other identifier: Sel-01
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 11

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.

Conditions

Pregnancy; Infertility; Auto-immune Thyroiditis

Keywords

Selenium; Pregnancy; Auto-immune thyroiditis; Post-partum thyroiditis; Miscarriage; Pre-eclampsia; Implantation and Pregnancy rate; Infertility

Outcome Measures

Primary Outcomes (1)

• Changes in TPOab and/or Tgab

  TPOab and Tgab titers will be measured using a ECLIA kit. Plasma selenium concentration will also be measured

  0 and 14 ± 2, 24 ± 2, 32± 2, 36± 2 weeks; and between 3° and 6° month after labour; and optionally 12° after labour

Secondary Outcomes (8)

• Changes in thyroid volume and echogenicity

  0 and 14 ± 2, 24 ± 2, 32± 2, 36± 2 weeks; and between 3° and 6° month after labour; and optionally 12° after labour

• Changes in thyroid hormones (TSH, FT4, FT3)

  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

  From the date of randomization until the date of first documented event

• Evaluation of Infant risks

  From the date of labour until the date of the first documented event

• Changes in of quality of life

  0 and 14 ± 2, 24 ± 2, 32± 2, 36± 2 weeks; and between 3° and 6° month after labour; and optionally 12° after labour

Study Arms (4)

Selenium

EXPERIMENTAL

Dietary Supplement: Selenium

Sugar Pill Placebo

PLACEBO COMPARATOR

Other: Sugar Pill Placebo

Selenium + L-Thyroxine (LT4)

EXPERIMENTAL

Other: Selenium + L-Thyroxine (LT4)

Sugar Pill Placebo + L-Thyroxine (LT4)

EXPERIMENTAL

Other: Sugar Pill Placebo + L-Thyroxine (LT4)

Interventions

Selenium 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

Also known as: Intervention I (Se)

Selenium

Sugar Pill Placebo 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.

Also known as: Intervention II (Plb)

Sugar Pill Placebo

Selenium + L-Thyroxine (LT4) 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)

Also known as: Intervention III (Se+LT4)

Selenium + L-Thyroxine (LT4)

Sugar Pill Placebo + L-Thyroxine (LT4) 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)

Also known as: Intervention IV (Plb + LT4)

Sugar Pill Placebo + L-Thyroxine (LT4)

Eligibility Criteria

• Age: 18 Years - 38 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Roma La Sapienza: lead

Study Sites (11)

Azienda ospedaliero-universitaria Careggi

Florence, 50134, Italy

Location

Istituto Auxologico Italiano

Milan, 20095, Italy

Location

Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

University Federico II

Naples, 80131, Italy

Location

University "Piemonte Orientale, A. Avogadro"

Novara, 28100, Italy

Location

Torvergata University of Rome - Ospedale S. Eugenio

Rome, 00145, Italy

Location

European Hospital

Rome, 00148, Italy

Location

Ospedale S. Giovanni Calibita Fatebenefratelli

Rome, 00153, Italy

Location

Department of Experimental Medicine, "Sapienza" University of Rome

Rome, 00161, Italy

Location

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

Rome, 00161, Italy

Location

Dpt of Experimental Medicine

Rome, 00161, Italy

Location

MeSH Terms

Conditions

Infertility; Postpartum Thyroiditis; Abortion, Spontaneous; Pre-Eclampsia

Interventions

Selenium; Sugars; Methods; phospholamban; Thyroxine

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases; Puerperal Disorders; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Thyroiditis, Autoimmune; Thyroiditis; Thyroid Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Hypertension, Pregnancy-Induced

Intervention Hierarchy (Ancestors)

Chalcogens; Elements; Inorganic Chemicals; Minerals; Carbohydrates; Investigative Techniques; Thyroid Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Andrea M Isidori, MD, PhD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Clinical Professor

Study Record Dates

• First Submitted: November 2, 2011
• First Posted: November 7, 2011
• Study Start: April 1, 2012
• Primary Completion: June 1, 2017
• Study Completion: January 1, 2018
• Last Updated: January 30, 2018

Record last verified: 2018-01

Locations

IT (11)