Renal Artery Dopplers in Twin Twin Transfusion Syndrome

July 16, 2018 updated by: Russell Miller, Columbia University

Are Renal Artery Doppler Indices Different Between Monochorionic Diamniotic Twins With Twin-twin Transfusion Syndrome and Monochorionic Diamniotic Twins Without Twin-twin Transfusion Syndrome?

Twin-twin transfusion syndrome (TTTS) is a complication affecting 10-15% of monochorionic, diamniotic (MCDA) twin pregnancies. Unevenly distributed blood flow across a shared placental circulation results in a volume-restricted donor twin and a volume-overloaded recipient twin, and TTTS has high perinatal morbidity and mortality without treatment.

Differential donor and recipient findings in TTTS can be observed upon ultrasound evaluation. TTTS is classified according to the Quintero staging system, which evaluates amniotic fluid volumes, fetal bladders, Doppler study of the umbilical artery and ductus venosus, and for the presence of hydrops or death. However, due to seemingly complex and variable disease pathophysiology, the Quintero system cannot predict outcomes on a case-by-case basis.

Prior studies have associated fetal renal artery Doppler ultrasound measurements with amniotic fluid volume in singleton pregnancies. In fetuses with placental insufficiency, adaptive circulatory changes maintain adequate oxygen delivery to vital organs such as the heart, brain, and adrenals, with a consequent deprivation to splanchnic organs. In the fetal kidney, as vascular resistance increases during hypoxia, renal perfusion decreases proportionately. These changes are reflected in renal artery Doppler findings. As these same adaptations are believed to occur in donor twins, renal artery Doppler studies may also be of value in the TTTS evaluation.

This study plans to perform renal artery Doppler assessments in MCDA twins complicated by TTTS, and compare them to measurements in gestational-age equivalent MCDA twins without TTTS. If findings differ significantly, it would support further investigation into the use of renal artery Doppler studies for the evaluation of complicated MCDA twins.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

TTTS, which complicates 10-15% of MCDA twin pregnancies, is characterized by a net imbalance of volume between twins, mediated through abnormal placental blood vessel anastomoses that connect the two placental circulations. Clinically, the "donor" twin develops features of anemia and hypovolemia, while the "recipient" twin shows signs of hypervolemia and hypertensive fluid overload. If untreated, the syndrome has a perinatal mortality rate as high as 80-100%. Although modern intrauterine therapies have improved the rates of fetal death, significant risks of morbidity and mortality remain even after treatment.

Twin-twin transfusion syndrome is most commonly classified according to a staging system developed by Quintero et al in 1999, which is based on discrete, categorical ultrasound findings (amniotic fluid volume, presence/absence of a fetal bladder, umbilical artery Doppler studies, fetal hydrops, and death). The system includes 5 stages ranging from mild disease with isolated discordant amniotic fluid volumes, to severe disease with demise of one or both twins. Although this system has some prognostic value, it also has significant limitations due to the highly complex physiologic conditions that are involved in the disease. For example, some criteria in the staging system are not consistently representative of fetal physiology. Additionally, the stages do not correlate well with overall perinatal survival or with outcomes following intrauterine therapies.

Recent work has demonstrated that the complex pathophysiology of twin-twin transfusion syndrome involves a discordant activation of the renin angiotensin system (RAS). RAS is normally important in fluid and salt regulation in both the adult and the fetus, and TTTS in marked hypovolemia and hypervolemia in monozygous fetuses within the same maternal environment. The renal RAS in the donor is up-regulated, presumably as a consequence of hypovolemia. The recipient is also exposed to high levels or RAS components, either due to the transfusion of these components from the donor via anastomoses, or via discordant placental RAS activation, resulting in a hypertensive, hypervolemic state.

Multiple studies have identified a correlation between Doppler assessment of the fetal renal artery and the development of oligohydramnios, a hypovolemic state, in singleton pregnancies. However, the use of renal artery Doppler studies has not yet been fully evaluated in twin gestations. In particular, it has not been evaluated in MCDA twin gestations complicated by TTTS, the pathophysiology of which involves significant alterations in fetal volume and fluid status.

This project is intended to serve as a single-center study to determine if there is indeed a difference in renal artery Doppler parameters in sets of MCDA twins with TTTS compared to sets of MCDA twins without TTTS. The identification of a significant difference would potentially provide support for further investigation into this measurement as a screening tool or prognostic indicator when applied to MCDA twin pregnancies.

Secondary goals of this study include: comparing donor to recipient renal artery Doppler findings among pregnancies with TTTS, evaluating serial renal artery Doppler findings over time per pregnancy, and evaluating pre- and post-therapy renal artery Doppler findings in those pregnancies undergoing therapy for TTTS.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
24

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

Female

Sampling Method

Non-Probability Sample

Study Population

The subject population will consist of pregnant women with monochorionic / diamniotic (MCDA) twin pregnancies with and without twin-twin transfusion syndrome (TTTS). This population is selected in order to investigate twin-twin transfusion syndrome, which is a disease process that is unique to pregnancies with monochorionic / diamniotic twins. Patients will be included in the study if they have a diagnosis of a MCDA twin gestation beyond the first trimester or pregnancy (greater than 14 weeks gestation).

Description

Inclusion Criteria:

  • pregnant women with monochorionic / diamniotic (MCDA) twin pregnancies with and without twin-twin transfusion syndrome (TTTS)
  • greater than 14 weeks gestation

Exclusion Criteria:

  • higher-order multiple gestation
  • sonographic evidence of a major structural fetal anomaly (exceptions to this structural fetal anomaly exclusion are acquired recipient twin cardiac changes that are known to be associated with TTTS - these cases may be considered for study inclusion)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
TTTS Cases
Cases of monochorionic / diamniotic twin pregnancies diagnosed with twin-twin transfusion syndrome.
Diagnostic test: Doppler ultrasound of fetal renal artery
Doppler ultrasound assessment of the proximal fetal renal artery to with measurement of the peak systolic velocity, resistive index, pulsatility index, and systolic/diastolic ratio.
MCDA Controls
Controls of monochorionic / diamniotic twin pregnancies without a diagnosis of twin-twin transfusion syndrome.
Diagnostic test: Doppler ultrasound of fetal renal artery
Doppler ultrasound assessment of the proximal fetal renal artery to with measurement of the peak systolic velocity, resistive index, pulsatility index, and systolic/diastolic ratio.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Fetal renal artery Doppler PSV for twin A
Time Frame: Obtained at the time of enrollment.
Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the peak systolic velocity for twin A.
Obtained at the time of enrollment.
Fetal renal artery Doppler RI for twin A
Time Frame: Obtained at the time of enrollment.
Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the resistive index for twin A.
Obtained at the time of enrollment.
Fetal renal artery Doppler PI for twin A
Time Frame: Obtained at the time of enrollment.
Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the pulsatility index for twin A.
Obtained at the time of enrollment.
Fetal renal artery Doppler PSV for twin B
Time Frame: Obtained at the time of enrollment.
Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the peak systolic velocity for twin B.
Obtained at the time of enrollment.
Fetal renal artery Doppler RI for twin B
Time Frame: Obtained at the time of enrollment.
Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the resistive index for twin B.
Obtained at the time of enrollment.
Fetal renal artery Doppler PI for twin B
Time Frame: Obtained at the time of enrollment.
Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the pulsatility index for twin B.
Obtained at the time of enrollment.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Post-laser fetal renal artery Doppler PSV for twin A
Time Frame: Obtained within one week following fetoscopic laser therapy for cases in which this treatment is provided.
Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the peak systolic velocity for twin A.
Obtained within one week following fetoscopic laser therapy for cases in which this treatment is provided.
Post-laser fetal renal artery Doppler RI for twin A
Time Frame: Obtained within one week following fetoscopic laser therapy for cases in which this treatment is provided.
Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the resistive index for twin A.
Obtained within one week following fetoscopic laser therapy for cases in which this treatment is provided.
Post-laser fetal renal artery Doppler PI for twin A
Time Frame: Obtained within one week following fetoscopic laser therapy for cases in which this treatment is provided.
Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the pulsatility index for twin A.
Obtained within one week following fetoscopic laser therapy for cases in which this treatment is provided.
Post-laser fetal renal artery Doppler PSV for twin B
Time Frame: Obtained within one week following fetoscopic laser therapy for cases in which this treatment is provided.
Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the peak systolic velocity for twin B.
Obtained within one week following fetoscopic laser therapy for cases in which this treatment is provided.
Post-laser fetal renal artery Doppler RI for twin B
Time Frame: Obtained within one week following fetoscopic laser therapy for cases in which this treatment is provided.
Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the resistive index for twin B.
Obtained within one week following fetoscopic laser therapy for cases in which this treatment is provided.
Post-laser fetal renal artery Doppler PI for twin B
Time Frame: Obtained within one week following fetoscopic laser therapy for cases in which this treatment is provided.
Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the pulsatility index for twin B.
Obtained within one week following fetoscopic laser therapy for cases in which this treatment is provided.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Columbia University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Joses Jain, MD, Columbia University
  • Principal Investigator: Russell Miller, MD, Columbia University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 9, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 21, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 7, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 22, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 28, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 18, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 16, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AAAQ9660

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

There is no plan to share individual participant data with other researchers.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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