NIRS Monitoring in Premature Infants
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|ClinicalTrials.gov Identifier: NCT02601339|
Recruitment Status : Recruiting
First Posted : November 10, 2015
Last Update Posted : November 10, 2015
|First Submitted Date||November 6, 2015|
|First Posted Date||November 10, 2015|
|Last Update Posted Date||November 10, 2015|
|Start Date||April 2015|
|Estimated Primary Completion Date||April 2017 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures
||FDNIRS-DCS [ Time Frame: 0-2 years old ]
FDNIRS-DCS measures cerebral blood flow, oxygen saturation and cerebral oxygen of metabolism noninvasively at the patient's bedside. Study "measurement" session will last between 20 and 60 minutes. For each visit, an FDNIRS-DCS monitor is softly placed in contact with the subject's head, which will not cause any discomfort to infants. Repeated measurements in the same location on the head and in different locations will be done. The monitor contains optical fibers (not electrical wires) that are connected to light sources and detectors. Using this monitor, a low-power red light is shined on the subject's skin. The light changes in the brain will be detected by sensitive detectors in which way CBF, CMRO2 and SO2 are then estimated.
|Original Primary Outcome Measures||Same as current|
|Change History||No Changes Posted|
|Current Secondary Outcome Measures||Not Provided|
|Original Secondary Outcome Measures||Not Provided|
|Current Other Outcome Measures||Not Provided|
|Original Other Outcome Measures||Not Provided|
|Brief Title||NIRS Monitoring in Premature Infants|
|Official Title||Beside Monitor of Cerebral Metabolism in Premature Infants With Intraventricular Hemorrhage and Post-Hemorrhagic Hydrocephalus|
This study is to use advanced near-infrared spectroscopy (NIRS) technology for monitoring cerebral blood flow (CBF) and cerebral oxygen metabolism (CMRO2) in newborns that developed germinal matrix-intraventricular hemorrhage (GM-IVH) and post-hemorrhagic hydrocephalus (PHH) at the bedside. We hypothesize that baseline cerebral metabolic dysfunction is a better biomarker for GM-IVH and PHH severity and response to PHH treatment.
This is a multi-center study at Massachusetts General Hospital (MGH), Brigham and Women's Hospital (BWH) and Boston Children's Hospital (BCH). The Partners Institutional review board (IRB) has approved the protocol to conduct study at BWH and MGH. The IRB protocol at BCH is at the final stage of approval.
Dr. Pei-Yi Lin receives the funding from National Institute of Health (NIH) to support the study and is the overall principal Investigator (PI) overseeing the study.
A. Introduction and specific aims:
Twelve percent of live births in the United States are premature, resulting in the need to care for some 500,000 premature infants(1,2). Germinal matrix-intraventricular hemorrhage (GM-IVH) is a major complication of prematurity, occurring in about 45% of extremely low birth weight infants (weight <1000 g)(3-5), and all grades are associated with adverse long-term neurological impairment(6,7). Even as improved neonatal intensive care and technological advances have increased the survival rate of extremely premature infants, the high incidence of GM-IVH has remained unchanged over the past decade(8,9). Premature infants are born with an immature capacity for cerebral hemodynamic regulation, putting the highly vascularized germinal matrix (GM) region at risk for hemorrhage (10,11). The special vascular morphology of the GM functions to supply the significant metabolic demands of a wave of cell proliferation and migration from the GM to the cortex prior to term gestational age (12,13). GM-IVH-induced suppression of this wave of cell proliferation is believed to be responsible for the later failure of the cerebrum to grow to normal volumes and subsequent delayed neurodevelopmental outcomes(14). A bedside tool for measuring CMRO2 may be of benefit in monitoring the evolution of GM-IVH, the response to therapy, and predicting future neurodevelopmental impairment (NDI).
In this study, we used the advanced near-infrared spectroscopy (NIRS) technology developed at MGH for monitoring cerebral oxygen metabolism (CMRO2) in newborns at the bedside. We hypothesize that baseline metabolic dysfunctions and cerebral blood flow are potential biomarkers for germinal matrix-intraventricular hemorrhage and posthemorrhagic hydrocephalus severity and response to PHH treatment.
To test our hypotheses, we will address the following specific aims:
To address this Aim in these two groups, we will:
The subject population will include neonates with and without IVH less than 3 months old correct age at first measure. We plan to perform measurements in 90 neonates enrolled at Brigham and Women's Hospital and 80 neonates at Boston Children's Hospital over the course of study.
Patient enrollment- For patient recruitment, one of the study members will identify potential subjects. Once the potential subject is identified, the study member will contact the attending physician and the bedside nurse overseeing the care of the potential subject to receive their permission for consenting. The parents of the potential subject will receive their permission to be contacted by study investigators.
In addition to all medical co-investigators, non-MD study members who are specifically educated and trained in NIRS technology, the goals of our study, and extensive training on the informed consent process, the intricacies of the Neonatal Intensive Care Unit (NICU) environment, and the delicate nature of NICU will qualify for recruiting.
Participation in the study is completely voluntary and may be terminated by a parent at any time. Any measurement results of the study are restricted to research investigation only and will not affect the health care provided by the hospital.
Near infrared spectroscopy:
Frequency domain NIRS (FDNIRS) quantifies hemoglobin concentration and oxygenation (SO2) in deep tissue by measuring the absorption and scattering coefficients of the examined tissue at multiple wavelengths in the red and near-infrared spectral region(15-17). Diffuse correlation spectroscopy (DCS) measures microvascular blood flow in deep tissue by quantifying the temporal intensity fluctuations of scattered light that arise from Doppler shifts induced by moving red blood cells(5,18,19). By combining these two technologies (FDNIRS-DCS), an index of the cerebral metabolic rate of oxygen (CMRO2i) is estimated(6,13).
The light from/to the NIRS devices is delivered to/from the head of the subject through fiber optic cables arranged within an optical probe. A rigid probe is used to maintain fixed source-detector separations, needed for accurate quantification of hemoglobin concentration and blood flow. All the lights exposure to the skin is within the American National Standards Institute (ANSI) Standards approved light levels. The laser light is not collimated, but rather is expanded/diffused at the probe end. This results in a Nominal Ocular Hazard Distance (NOHD) of 5-7 cm, which is lower than the 10 cm focusing distance of the retina. Hence, eye protection is not required the DCS devices connected to the probes.
The FDNIRS and DCS devices and the combined system are maintained by MGH investigators at the Optics Division of Martinos center for Biomedical Imaging and can be used in the sites and locations approved in the protocols. MGH, BWH and BCH Biomedical Engineering test the devices annually and regularly.
Measurement procedure(20)- Measurements will be done with a flexible time frame and preferably when the subject is sleeping. NIRS measurements will be done in up to 7 locations including bilateral frontal, parietal and temporal regions and repeated up to 5 times, for a total time at the bedside not longer than 30 minutes.
All the infants enrolled in the study will be measured up to once a day for the duration of their hospital stay if clinically feasible. If the subject in the PHH and VC groups is scheduled for any surgery or treatment to treat the progressive hydrocephalus, we will perform additional short measurements to monitor the response to treatment. These shorter measurement session will not exceed 30 minutes and no more than four times in the 24 hours immediately after treatment. . In the days following the intervention of interest (after the initial 24-hour post-operative or post-treatment window), the measurement schedule will return to regular basis.
Subjects in VC and PHH groups will have clinical follow-up visits (that are independent of the study) to monitor the treatment and evolution of their condition. We will attempt to schedule a follow-up FDNIRS-DCS measurement on the same day that study subjects return to the hospital for clinical imaging or consults.
C. Adverse Event Criteria and Reporting Procedures:
Adverse events deemed related to participation in the study will be documented and reported to the IRB promptly (within 7 calendar days). Unrelated adverse events, which include any untoward medical occurrence that may present itself during the conduct of our measurements without a casual relationship with the study procedures, but occurring in our presence will also be documented and reported to IRB at the time of continuing review. Physician investigators/the PI will determine relatedness based upon the event, timing, plausibility, and other medical problems and/or possible explanations for the event. Serious adverse events (SAE) are those that result in death, a life-threatening experience, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity or a congenital anomaly/birth defect, or that require medical or surgical intervention to prevent any of these outcomes. To ensure that any SAEs or complications potentially related to study procedures are promptly identified, the PIs will educate study coordinators about hospital-specific SAEs and will instruct them to report to them any potential SAE or complication immediately (on the day either is identified).
F. Data Management Methods The study's Data and Safety Monitoring Plan and Standard Operating Procedures have been developed to address issues of safety, recruitment and enrollment, data collection and management, and quality control. Highlights related to data management are below.
Subjects' privacy and confidentiality will be protected at all times in accordance with all Partners Human Research Committee (PHRC) and Health Insurance Portability and Accountability Act (HIPAA) standards and requirements.
Highlights related to data management are below. Subjects' privacy and confidentiality will be protected at all times. When an infant is enrolled, a parent will sign a consent form and the infant will be assigned a study identification (ID) number, which will not include name, initials, or any other potential identifiers. The Study ID Tracking Log, which lists the medical record numbers corresponding to the subject identification codes, will be stored electronically in a separate secure file. Only study staff listed on the protocol will have access to this site.
A second secure electronic database is used to store infants' clinical information (diagnostic tests, imaging, etc.) as well as measurement information (birth date, date of measurement, measurement location, which instruments were used, bedside notes, etc.). Members of the study team involved in data analysis will have access to the clinical history of all enrolled infants as long as they have HIPAA training and active Collaborative Institutional Training Initiative (CITI) training certificates.
Study staff will maintain all IRB materials and records electronically, including the regulatory binder. Any regulatory documentation that must be stored on paper will be kept in a binder on sites, and will not contain identifying information. The portions of the Regulatory Binders that are maintained on paper and the consent forms will be filed in the research record, in a locked cabinet in a locked room on sites. One copy of the signed consent will be given to the parent, and another copy will be filed in the infant's medical record.
|Study Design||Observational Model: Cohort
Time Perspective: Prospective
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Non-Probability Sample|
|Study Population||The subject population will include premature and full-term neonates with and without GM-IVH less than 3 months old corrected age at first measure.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Estimated Completion Date||April 2020|
|Estimated Primary Completion Date||April 2017 (Final data collection date for primary outcome measure)|
Exclusion criteria for VC group: known or suspected metabolic disorder or neoplasm; congenital heart disease.
|Ages||up to 3 Months (Child)|
|Accepts Healthy Volunteers||Yes|
|Listed Location Countries||United States|
|Removed Location Countries|
|Other Study ID Numbers||2014P001713
1K99HD083512-01 ( U.S. NIH Grant/Contract )
P00014042 ( Other Identifier: Boston Children's Hospital )
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||Pei-Yi Lin, Massachusetts General Hospital|
|Study Sponsor||Massachusetts General Hospital|
|PRS Account||Massachusetts General Hospital|
|Verification Date||November 2015|