Relation Between Subclinical Hypothyroidism and Outcome of Pregnancy (GravThyr)

This study is currently recruiting participants.
Verified November 2012 by Naestved Hospital
Sponsor:
Collaborator:
University of Copenhagen
Information provided by (Responsible Party):
Anne-Dorthe Feldthusen, Naestved Hospital
ClinicalTrials.gov Identifier:
NCT01335802
First received: April 11, 2011
Last updated: November 19, 2012
Last verified: November 2012
  Purpose

Studies have demonstrated a relationship between subclinical hypothyroidism and obstetrics complications like preterm delivery, pre-eclampsia, placental abruption and stillbirth. Subclinical hypothyroidism and positive thyroperoxidase antibodies (TPOab) may increase the risk of early spontaneous abortion before 12 weeks of gestation. But there is not a consensus if the prevalence of TPOab should be treated before and during pregnancy when the level of thyroid-stimulating hormone (TSH) is normal.

Thyroid hormones are regulators of the mitochondrial activity and our research group has previously shown that subclinical hypothyroidism affects mitochondrial activity.

The hypothesis:

Subclinical hypothyroidism causes early spontaneous abortion and or complications in pregnancy like pre-eclampsia because of mitochondrial dysfunction


Condition
Abortion, Spontaneous
Pregnancy Complications
Subclinical Hypothyroidism

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Relation Between Thyroid Hormone Stimulated Mitochondrial Function and Spontaneous Abortion and Complications of Pregnancy in Subclinical Hypothyroidism

Resource links provided by NLM:


Further study details as provided by Naestved Hospital:

Primary Outcome Measures:
  • Subclinical hypothyroidism [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    When the women participate the General Suburban Population Study (GeSuS) s-TSH are estimated. The women will be invited by letter if they match the inclusion criteria. There will only be one visit at the hospital for new bloodsample (flow cytometry) and measurement of oxygen consumption.

  • Pre-eclampsia [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Does pregnant women with subclinical hypothyroidism have mitochondrial dysfunction which could explain the higher frequency of gestational hypertension and pre-eclampsia? Pregnant women who consult the department of obstetrics are invited to participate (interview and a blood sample).


Secondary Outcome Measures:
  • Mitochondrial dysfunction [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Measure by flow cytometry


Estimated Enrollment: 200
Study Start Date: October 2010
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts
Subclinical hypothyroidim
Women having subclinical hypothyroidism and/or TPOab-positive.
Controls
Women having normal levels of TSH and TPOab-negative.

Detailed Description:

The aim is to estimate the relationship between SH and spontaneous abortion and/or obstetric complications because of mitochondrial dysfunction.

  1. A prospective study where data from the General Suburban Population Study in Naestved will be analyzed to measure the frequency of subclinical hypothyroidism (SH) and TPOab. SH is defined as raised serum concentrations of TSH > 3,4 mU/l and normal levels of free T4 and T3. A cut-off of 60 mU/l is used for TPOab.
  2. To estimate the relationship between SH or TPOab and early spontaneous abortion and pregnancy outcome. Inclusion of women who have experienced a minimum of one early spontaneous abortion and between 20 and 50 years old: 50 women who have SU and/or TPOab-positive and 50 women who have normal levels of TSH and TPOab-negative. The basal oxygen consumption will be measured and mitochondrial functions will be determined by flow cytometry.
  3. To estimate the prevalence of gestational hypertension and pre-eclampsia among pregnant women with subclinical hypothyroidism and estimate the mitochondrial function. A minimum of 100 pregnant women without any thyroid disease or diabetes will be included.

Early spontaneous abortion is defined as abortion before 12 weeks of gestation. Obstetrics complications are defined as pre-eclampsia (proteinuria, oedema, hypertension), pregnancy-induced hypertension, placental insufficience (IUGR) and abruption, preterm delivery and stillbirth. Those complications will be analyzed from the data of the obstetric journals.

Measurement of oxygen consumption:

Respiratory gas analysis and volume measurements were performed with a canopy connected by a triple V (flow⁄gas sensor) to an Oxycon apparatus (Jaeger Oxycon Champion, Breda, the Netherlands). The equipment was calibrated before each test to compensate for ambient conditions such as air pressure, temperature and humidity. Basal VO2 was measured after at least 6 hours fasting. Before the test the individual resting pulse was established and the participants rested for about 30 min in a chair. The test room was quiet and the lighting was subdued. The subjects were given sufficient time to become familiarized with the equipment and the procedures and the test was initiated when the resting pulse was achieved. Oxygen consumption was measured when the uptake per minute remained constant. Measurements were performed for repeated periods of 30 seconds for 20 minutes. The method for recording oxygen uptake had a within-day variation of 0.8 % and a day-to-day variation of 5.8 %.

Measurement of mitochondrial mass (MM) and mitochondrial membrane potential (MMP) by flow cytometry:

Venous blood was drawn from the patient in EDTA Vacutainer tubes. From each patient 2 samples of 100 µl of blood were processed. One unstained control tube and one stained were analyzed.

The samples to be stained were added 1 µl Pacific Blue Mouse Anti-Human anti-CD14 (BD Biosciences, Denmark) and mixed. The tubes were incubated for 30 minutes at room temperature protected from direct light and subsequently washed.

The stained cells were resuspended in 890 µl PBS and added 10 µl 1 µM MTG (MitoTracker Green FM, Invitrogen A/S, Denmark) and 100 µl 1 µM TMRM (Tetramethylrhodamine methyl ester, Invitrogen A/S, Denmark). All stock solutions were dissolved in DMSO (dimethyl sulfoxide) and working solutions were diluted in PBS. After mixing samples were incubated for 30 minutes at room temperature in the dark.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Part 2: Fertile women from the General Suburban Population Study in Naestved (GeSuS), Region Zealand, Denmark.

Part 3: Pregnant women (GA>27) who are consulting the department of obstetrics, Naestved Hospital.

Criteria

Part 2:

Inclusion Criteria:

Women who had experienced a minimum of one early spontaneous abortion and between 20 and 50 years old: 80 women who have subclinical hypothyroidism defined as raised serum concentrations of TSH > 3,4 mU/l and normal levels of free T4 and T3 or TPOab-positive and 80 women who have normal levels of TSH and TPOab-negative.

Exclusion Criteria:

  • Women with metabolic disease, diabetes or psychiatric disease.
  • Women using medicine against hypo- or hyperthyroidism.
  • Women who never give birth or age more than 50 years.

Part 3:

Inclusion Criteria:

  • Pregnant women (3rd trimester)

Exclusion Criteria:

  • Women with metabolic disease, diabetes or psychiatric disease.
  • Women using medicine against hypo- or hyperthyroidism.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01335802

Contacts
Contact: Anne-Dorthe Feldthusen, MD +45 5651 4424 afd@regionsjaelland.dk
Contact: Jan Kvetny, MD DMSc +45 5651 4136 jkve@regionsjaelland.dk

Locations
Denmark
Naestved Hospital Recruiting
Naestved, Denmark, 4700
Contact: Anne-Dorthe Feldthusen, MD       afd@regionsjaelland.dk   
Sponsors and Collaborators
Naestved Hospital
University of Copenhagen
Investigators
Principal Investigator: Jan Kvetny, MD, DMSc Department of Internal Medicine & Faculty of Health Sciences, University of Copenhagen
  More Information

No publications provided

Responsible Party: Anne-Dorthe Feldthusen, MD, Naestved Hospital
ClinicalTrials.gov Identifier: NCT01335802     History of Changes
Other Study ID Numbers: SJ-177
Study First Received: April 11, 2011
Last Updated: November 19, 2012
Health Authority: Denmark: National Board of Health

Keywords provided by Naestved Hospital:
Abortion, Spontaneous
Pre-eclampsia
Gestational hypertension
Pregnancy Complications
Subclinical hypothyroidism
Thyroperoxidase antibodies (TPOab)
Mitochondrial dysfunction

Additional relevant MeSH terms:
Abortion, Spontaneous
Hypothyroidism
Pregnancy Complications
Thyroid Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on April 20, 2014