Recurrent Pregnancy LossEarly Phase 1NCT03106935
Recurrent Pregnancy Loss and Thyroid Disease
A Early Phase 1 study testing Levothyroxine in people with Recurrent Pregnancy Loss, run by Second Affiliated Hospital of Soochow University at 1 site in China.
Trial summary
The present study is divided into two groups ,one is the patients with subclinical hypothyroidism who has TPO antibody positive women with TSH concentrations > 2.5 mU/L and below the upper limit of the pregnancy specific reference range ,another is TPO antibody negative with TSH concentrations greater than the… Read more about this study
- Who is it for?
- Ages 18 to 39 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Recurrent Pregnancy Loss
- What is being tested?
- Levothyroxine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 1 siteChina
- Study dates
- Jul 2015to Jun 2018
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 39 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- having a diagnosis of RPL (two or more consecutive or non-consecutive first-trimester losses)
- be.ing aged 18-39 years at randomisation
- trying to conceive naturally
- willing and able to give informed consent
Who cannot join
- they were unable to conceive naturally (as confirmed by urinary pregnancy tests) within 1 year of recruitment or before the end of the randomisation period in the trial, whichever came earlier
- they had antiphospholipid syndrome [lupus anticoagulant and/or anticardiolipin antibodies (immunoglobulin G or immunoglobulin M)]; other recognised thrombophilic conditions (testing according to usual clinic practice) l they had uterine cavity abnormalities (as assessed by ultrasound, hysterosonography, hysterosalpingogram or hysteroscopy)
- they had abnormal parental karyotype
- they had other identifiable causes of RPL (tests initiated only if clinically indicated) such as diabetes or systemic lupus erythematosus
- they had any contraindications to Levothyroxine use
Trial locations and contacts
1 site in 1 country.
China1 site
Second Affiliated Hospital of Soochow University
Suzhou, Jiangsu, 215004
About this study
Official title: Effect of Levothyroxine Treatment on Pregnancy Outcome in RPL Women With Subclinical Hypothyroidism
The present study is divided into two groups ,one is the patients with subclinical hypothyroidism who has TPO antibody positive women with TSH concentrations > 2.5 mU/L and below the upper limit of the pregnancy specific reference range ,another is TPO antibody negative with TSH concentrations greater than the pregnancy specific reference range and below 10.0 mU/L.The two groups are randomized into either the LT4 treatment group or control group by the use of a computer-generated list.
The aim of our study is to determine whether the use of levothyroxine is beneficial in patients with subclinical hypothyroidism in two groups。
Read the detailed description
Many studies have stratified the risk imparted by hypothyroidism according to TPOAb status, and consistently show that this risk is higher in TPOAb positive women. Some data also suggest that the adverse impact associated with maternal TSH levels is apparent at lower TSH elevations in women known to be TPOAb positive compared to women who are TPOAb negative. Furthermore, studies suggest a reduction in pregnancy loss when TPOAb positive women are treated with levothyroxine, even when biochemically euthyroid. Intervention trials have not been performed in TPOAb negative women. A etiology analysis process,from June 2010 to June 2015 in The Second Affiliated Hospital of Soochow University, were showed that 22.2% of total 917 cases who had RPL history present as abnormal serum TSH level or positive TPOAb, while 36.6% of 523 cases who repregnancy present as abnormal.This present study is divided into two groups ,one is the patients with subclinical hypothyroidism who hasTPO antibody positive women with TSH concentrations > 2.5 mU/L and below the upper limit of the pregnancy specific reference range ,another is TPO antibody negative with TSH concentrations greater than the pregnancy specific reference range and below 10.0 mU/L.The two groups are randomized into either the LT4 treatment group or control group by the use of a computer-generated list.For the LT4 treatment group, 50μg LT4 (Merck Serono, Geneva,Switzerland) was administered every morning from the first day of diagnosed as subclinical hypothyroidism and continued up to the day of serum β-HCG measurement.If pregnancy was confirmed, levothyroxine dose need to increase 25-30% and be adjusted according to the pregnancy specific reference range ( T1 0.1-2.5mIU/L,T2 0.2-3.0mIU/L, T3 0.3-3.0mIU/L).For the control group ,women with subclinical hypothyroidism are not given any drugs . The aim of our study is to determine whether the use of levothyroxine is beneficial in patients with subclinical hypothyroidism who has TPO antibody positive women with TSH concentrations > 2.5 mU/L and below the upper limit of the pregnancy specific reference range or TPO antibody negative with TSH concentrations greater than the pregnancy specific reference range and below 10.0 mU/L.
- Conditions
- Recurrent Pregnancy Loss
- Being tested
- Levothyroxine
- Keywords
- recurrent pregnancy loss, Clinical hypothyroidism, Subclinical hypothyroidism, thyroid stimulating hormone, thyroid peroxidase antibody, Levothyroxine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevothyroxineDrug
Also called LT4
Levothyroxine is an orodispersible tablet.For the LT4 treatment group, 50μg LT4 (Merck Serono, Geneva,Switzerland) was administered every morning from the first day of diagnosed as subclinical hypothyroidism and continued up to the day of serum β-HCG measurement.If pregnancy was confirmed, levothyroxine dose need to increase 25-30% and adjusted according to the pregnancy specific reference range ( T1 0.1-2.5mIU/L,T2 0.2-3.0mIU/L, T3 0.3-3.0mIU/L) .
| Study group | Role | What they receive |
|---|---|---|
| Obstet Gynecol,SecondSoochowU | Active comparator | Levothyroxine is an orodispersible tablet.For the LT4 treatment group, 50μg LT4 (Merck Serono, Geneva,Switzerland) was administered every morning from the first day of diagnosed as subclinical hypothyroidism and continued up to the day of serum β-HCG measurement.If pregnancy was confirmed, levothyroxine dose need to increase 25-30% and adjusted according to the pregnancy specific reference range ( T1 0.1-2.5mIU/L,T2 0.2-3.0mIU/L, T3 0.3-3.0mIU/L) . Receives: Drug: Levothyroxine |
| reproductive center,SecondSoochowU | No intervention | For the control group ,women with subclinical hypothyroidism are not given any drugs . |
What is being measured
The primary outcome is the main question the study is designed to answer.
Gestational week at delivery
The research doctor site telephoned every participant 2 weeks after the expected date of delivery to obtain pregnancy outcome data.
Measured: 28 weeks
Newborn birth weight
The research doctor site telephoned every participant 2 weeks after the expected date of delivery to obtain newborn birth weight.
Measured: at birth
APGAR Score at birth
The APGAR (Appearance, Pulse, Grimace, Activity, Respiration) scale is determined by evaluating the newborn baby on five simple criteria on a scale from zero to two, then summing up the five values thus obtained. The resulting APGAR score ranges from zero to 10.
Measured: at birth
Secondary outcomes (3)
Number of clinical pregnancy at 6-8 weeks (defined as the presence of a gestational sac, with or without a yolk sac or fetal pole)
The research doctor site telephoned every participant at between 6 and 7 weeks of gestation, to ensure there were arrangements for an ultrasound appointment with her usual carers, before 8 weeks of gestation. If an appointment had not been booked, the research doctor assisted with booking. The research doctor telephoned each participant again between 3 and 5 days after the scheduled date of the ultrasound appointment, to obtain details of the observations of a gestational sac.
Measured: 8 weeks
Number of ongoing pregnancy at 12 weeks (defined as the presence of a fetal heartbeat)
The research doctor site telephoned each participant between 10 and 12 weeks of gestation, to ensure there were arrangements for an ultrasound appointment with her usual carers, at between 12 and 14 weeks of gestation. As previously, the research doctor assisted with booking an appointment if necessary, and telephoned the participant afterwards to obtain details of variables such as fetal heartbeat. The research doctor also recorded the expected date of delivery at this stage.
Measured: 12weeks
Number of miscarriage (defined as loss of pregnancy before 28 weeks of gestation).
The research doctor site telephoned each participant before28 weeks of gestation, to obtain their pregnancy outcomes such as miscarriage.
Measured: 28 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2017
- Study startJul 2015
- Primary completionDec 2017 (estimated)
- Study completionJun 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Recurrent Pregnancy LossStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Second Affiliated Hospital of Soochow University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, ZHANG Hong, Second Affiliated Hospital of Soochow University
- Investigators
- ZHANG Hong, Ph.D,M.D, Principal investigator, a staff of The Second Affiliated Hospital of Soochow University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03106935
- Sponsor's protocol ID
- The Second Affiliated Hospital
- Status last verified
- Apr 2017
- First submitted
- 27 Feb 2017
- Last updated
- 12 Apr 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- Individual data sharing
- Undecided
Publications
Zhu LY, Chen X, Xu ZZ, Xu L, Mao T, Zhang H. Changes and clinical significance of peripheral blood helper T lymphocyte and natural killer (NK) cells in unexplained recurrent spontaneous abortion (URSA) patients after abortion and successful pregnancy. Clin Exp Obstet Gynecol. 2015;42(1):62-6.
PubMed 25864284Wu S, Zhang H, Tian J, Liu L, Dong Y, Mao T. Expression of kisspeptin/GPR54 and PIBF/PR in the first trimester trophoblast and decidua of women with recurrent spontaneous abortion. Pathol Res Pract. 2014 Jan;210(1):47-54. doi: 10.1016/j.prp.2013.09.017. Epub 2013 Oct 26.
PubMed 24225150Zhang H, Long Q, Ling L, Gao A, Li H, Lin Q. Elevated expression of KiSS-1 in placenta of preeclampsia and its effect on trophoblast. Reprod Biol. 2011 Jul;11(2):99-115. doi: 10.1016/s1642-431x(12)60048-5.
PubMed 21804632Mao C, Zhang H, Xiao D, Zhu L, Ding Y, Zhang Y, Wu L, Xu Z, Zhang L. Perinatal nicotine exposure alters AT 1 and AT 2 receptor expression pattern in the brain of fetal and offspring rats. Brain Res. 2008 Dec 3;1243:47-52. doi: 10.1016/j.brainres.2008.09.060. Epub 2008 Oct 2.
PubMed 18926802
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Levothyroxine Treatment on Pregnancy Outcome in RPL Women With Subclinical Hypothyroidism
- ClinicalTrials.gov ID
- NCT03106935
- Acronym / sponsor ID
- The Second Affiliated Hospital
- Conditions
- Recurrent Pregnancy Loss
- Keywords
- recurrent pregnancy loss, Clinical hypothyroidism, Subclinical hypothyroidism, thyroid stimulating hormone, thyroid peroxidase antibody, Levothyroxine
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital of Soochow UniversityUniversity, hospital or other
- Study start
- Jul 2015
- Primary completion
- Dec 2017 (estimated)
- Study completion
- Jun 2018 (estimated)
- First posted
- 11 Apr 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The present study is divided into two groups ,one is the patients with subclinical hypothyroidism who has TPO antibody positive women with TSH concentrations > 2.5 mU/L and below the upper limit of the pregnancy specific reference range ,another is TPO antibody negative with TSH concentrations greater than the pregnancy specific reference range and below 10.0 mU/L.The two groups are randomized into either the LT4 treatment group or control group by the use of a computer-generated list.
The aim of our study is to determine whether the use of levothyroxine is beneficial in patients with subclinical hypothyroidism in two groups。
Detailed description
Many studies have stratified the risk imparted by hypothyroidism according to TPOAb status, and consistently show that this risk is higher in TPOAb positive women. Some data also suggest that the adverse impact associated with maternal TSH levels is apparent at lower TSH elevations in women known to be TPOAb positive compared to women who are TPOAb negative. Furthermore, studies suggest a reduction in pregnancy loss when TPOAb positive women are treated with levothyroxine, even when biochemically euthyroid. Intervention trials have not been performed in TPOAb negative women. A etiology analysis process,from June 2010 to June 2015 in The Second Affiliated Hospital of Soochow University, were showed that 22.2% of total 917 cases who had RPL history present as abnormal serum TSH level or positive TPOAb, while 36.6% of 523 cases who repregnancy present as abnormal.This present study is divided into two groups ,one is the patients with subclinical hypothyroidism who hasTPO antibody positive women with TSH concentrations > 2.5 mU/L and below the upper limit of the pregnancy specific reference range ,another is TPO antibody negative with TSH concentrations greater than the pregnancy specific reference range and below 10.0 mU/L.The two groups are randomized into either the LT4 treatment group or control group by the use of a computer-generated list.For the LT4 treatment group, 50μg LT4 (Merck Serono, Geneva,Switzerland) was administered every morning from the first day of diagnosed as subclinical hypothyroidism and continued up to the day of serum β-HCG measurement.If pregnancy was confirmed, levothyroxine dose need to increase 25-30% and be adjusted according to the pregnancy specific reference range ( T1 0.1-2.5mIU/L,T2 0.2-3.0mIU/L, T3 0.3-3.0mIU/L).For the control group ,women with subclinical hypothyroidism are not given any drugs . The aim of our study is to determine whether the use of levothyroxine is beneficial in patients with subclinical hypothyroidism who has TPO antibody positive women with TSH concentrations > 2.5 mU/L and below the upper limit of the pregnancy specific reference range or TPO antibody negative with TSH concentrations greater than the pregnancy specific reference range and below 10.0 mU/L.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Obstet Gynecol,SecondSoochowU | Active comparator | Drug: LevothyroxineLevothyroxine is an orodispersible tablet.For the LT4 treatment group, 50μg LT4 (Merck Serono, Geneva,Switzerland) was administered every morning from the first day of diagnosed as subclinical hypothyroidism and continued up to the day of serum β-HCG measurement.If pregnancy was confirmed, levothyroxine dose need to increase 25-30% and adjusted according to the pregnancy specific reference range ( T1 0.1-2.5mIU/L,T2 0.2-3.0mIU/L, T3 0.3-3.0mIU/L) . |
| reproductive center,SecondSoochowU | No intervention | –For the control group ,women with subclinical hypothyroidism are not given any drugs . |
Who may qualify
- Ages
- 18 to 39 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- having a diagnosis of RPL (two or more consecutive or non-consecutive first-trimester losses)
- be.ing aged 18-39 years at randomisation
- trying to conceive naturally
- willing and able to give informed consent
Key exclusion criteria (5 listed)
- they were unable to conceive naturally (as confirmed by urinary pregnancy tests) within 1 year of recruitment or before the end of the randomisation period in the trial, whichever came earlier
- they had antiphospholipid syndrome [lupus anticoagulant and/or anticardiolipin antibodies (immunoglobulin G or immunoglobulin M)]; other recognised thrombophilic conditions (testing according to usual clinic practice) l they had uterine cavity abnormalities (as assessed by ultrasound, hysterosonography, hysterosalpingogram or hysteroscopy)
- they had abnormal parental karyotype
- they had other identifiable causes of RPL (tests initiated only if clinically indicated) such as diabetes or systemic lupus erythematosus
- they had any contraindications to Levothyroxine use
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LevothyroxineAlso: LT4Levothyroxine is an orodispersible tablet.For the LT4 treatment group, 50μg LT4 (Merck Serono, Geneva,Switzerland) was administered every morning from the first day of diagnosed as subclinical hypothyroidism and continued up to the day of serum β-HCG measurement.If pregnancy was confirmed, levothyroxine dose need to increase 25-30% and adjusted according to the pregnancy specific reference range ( T1 0.1-2.5mIU/L,T2 0.2-3.0mIU/L, T3 0.3-3.0mIU/L) . | Drug | Obstet Gynecol,SecondSoochowU |
Primary outcome
Gestational week at delivery
Time frame: 28 weeks
The research doctor site telephoned every participant 2 weeks after the expected date of delivery to obtain pregnancy outcome data.
Newborn birth weight
Time frame: at birth
The research doctor site telephoned every participant 2 weeks after the expected date of delivery to obtain newborn birth weight.
APGAR Score at birth
Time frame: at birth
The APGAR (Appearance, Pulse, Grimace, Activity, Respiration) scale is determined by evaluating the newborn baby on five simple criteria on a scale from zero to two, then summing up the five values thus obtained. The resulting APGAR score ranges from zero to 10.
3 secondary outcomes
Number of clinical pregnancy at 6-8 weeks (defined as the presence of a gestational sac, with or without a yolk sac or fetal pole)
Time frame: 8 weeks
Number of ongoing pregnancy at 12 weeks (defined as the presence of a fetal heartbeat)
Time frame: 12weeks
Number of miscarriage (defined as loss of pregnancy before 28 weeks of gestation).
Time frame: 28 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2017.
- Background: PubMed 25864284Zhu LY, Chen X, Xu ZZ, Xu L, Mao T, Zhang H. Changes and clinical significance of peripheral blood helper T lymphocyte and natural killer (NK) cells in unexplained recurrent spontaneous abortion (URSA) patients after abortion and successful pregnancy. Clin Exp Obstet Gynecol. 2015;42(1):62-6.
- Background: PubMed 24225150Wu S, Zhang H, Tian J, Liu L, Dong Y, Mao T. Expression of kisspeptin/GPR54 and PIBF/PR in the first trimester trophoblast and decidua of women with recurrent spontaneous abortion. Pathol Res Pract. 2014 Jan;210(1):47-54. doi: 10.1016/j.prp.2013.09.017. Epub 2013 Oct 26.
- Background: PubMed 21804632Zhang H, Long Q, Ling L, Gao A, Li H, Lin Q. Elevated expression of KiSS-1 in placenta of preeclampsia and its effect on trophoblast. Reprod Biol. 2011 Jul;11(2):99-115. doi: 10.1016/s1642-431x(12)60048-5.
- Background: PubMed 18926802Mao C, Zhang H, Xiao D, Zhu L, Ding Y, Zhang Y, Wu L, Xu Z, Zhang L. Perinatal nicotine exposure alters AT 1 and AT 2 receptor expression pattern in the brain of fetal and offspring rats. Brain Res. 2008 Dec 3;1243:47-52. doi: 10.1016/j.brainres.2008.09.060. Epub 2008 Oct 2.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
ZHANG Hong, Ph.D,M.D principal investigator
a staff of The Second Affiliated Hospital of Soochow University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Levothyroxine in people with Recurrent Pregnancy Loss, run by Second Affiliated Hospital of Soochow University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Gestational week at delivery (time frame: 28 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03106935, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2017.