We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Biokinetics Study for Tc-99m MDP in Pediatric Molecular Imaging

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03107247
Recruitment Status : Completed
First Posted : April 11, 2017
Last Update Posted : October 7, 2021
Sponsor:
Collaborators:
National Institute for Biomedical Imaging and Bioengineering (NIBIB)
Johns Hopkins University
University of Florida
Information provided by (Responsible Party):
Frederic Fahey, Boston Children's Hospital

Brief Summary:

The radiation exposure resulting from medical imaging is a topic of some concern. Nuclear medicine provides potentially life-saving information regarding physiological processes, and is of particular value in children where the rapid and unequivocal diagnosis of pathological concerns is essential for the health of these patients. The overall objective of this investigation is to optimize pediatric patient absorbed dose by keeping it as low as possible while maintaining excellent diagnostic quality of nuclear medicine images. This is particularly important since children are at increased risk due to the enhanced radiosensitivity of their tissues and the longer time-period over which radiation effects may manifest. Current dosimetric estimations in children are based on either animal biokinetic or pharmacokinetic data from adults due to paucity of data that exists for children. This situation will be improved through the following specific aims:

  • Collect image-based pharmacokinetic (PK) data from patient volunteers in different age groups scheduled for routine nuclear medicine studies for Tc-99m methylene diphosphonate (MDP), a radiopharmaceutical commonly used in pediatric nuclear medicine
  • Pool and analyze the data for different age groups for each radiopharmaceuticals and
  • Generate biokinetic models to be used in subsequent dosimetric models for the optimization of pediatric nuclear medicine procedures.

Since inadequate pharmacokinetic data currently exist in these patients, the investigators will use the data acquired in this study to establish PK models applicable to different age categories. Data on the pharmacokinetics of agents used in pediatric nuclear medicine are almost completely lacking. Internationally adopted dose coefficients (mSv/MBq) for pediatric nuclear medicine make age-dependent adjustments only for patient size and anatomical differences, while time-dependent kinetics from adult PK models are assumed due to the lack of kinetic data for children. The data obtained from this study will make it possible for the first time to determine how the PK in pediatric patients differs from adults. This will be done for Tc-99m MDP, a radiopharmaceutical commonly used for pediatric nuclear medicine imaging. The overall hope is that results will allow the molecular imaging community to implement pediatric dose-reduction approaches that substantially improve upon current guidelines pointing to future technological advances that could yield even greater dose-reduction while simultaneously improving diagnostic image quality.


Condition or disease Intervention/treatment Phase
Skeletal Injury Drug: Tc-99M MDP Other: Modification in acquisition protocol Phase 4

Detailed Description:

The overall objective of this investigation is to optimize pediatric patient absorbed dose by keeping it as low as possible while maintaining and even improving the diagnostic quality of nuclear medicine images. Current dosimetric estimations in children are based on either animal biokinetic or pharmacokinetic data from adults. This is due to paucity of data that exists specifically for children. This situation will be improved through the following specific aims:

  • Collect imaging-based pharmacokinetic (PK) data from patient volunteers in different age groups scheduled for selected, routine nuclear medicine studies for Tc-99m methylene diphosphonate (MDP), a radiopharmaceutical commonly used in pediatric nuclear medicine
  • Pool and analyze the data for different age groups for each radiopharmaceuticals and
  • Generate biokinetic models to be used in subsequent dosimetric models for the optimization of pediatric nuclear medicine procedures.

Pediatric absorbed dose estimates that are typically reported apply adult PK data with pediatric variations in body size and anatomy but not for differences in physiology between children and adults. Depending on the diagnostic agent, such differences can be of greater impact than anatomical differences. The investigators will acquire image data that will allow us to develop PK models for Tc-99m MDP, a radiopharmaceutical routinely used in pediatric nuclear medicine fr skeletal imaging. Patients undergoing standard of care imaging will be asked to consent to being imaged at one additional time point, either prior or subsequent to the time typical for clinical imaging. No patient will be asked to undergo more than one additional imaging time-point.

It is important to note that the patient volunteers will not receive any additional radiation exposure for inclusion in this study. They are only being ask to allow imaging at an additional time point.

Patients ages 1-16 years old will be included. Routine imaging will be collected 3-4 h post-administration with a dual-detector rotating gamma camera. Half of the subjects will also be imaged between 30 and 90 min, PA. The 2nd half will be at 4-6 h, post-administration.

The additional imaging will occur on the day of the clinically indicated procedure. Other than that, there is no timeline associated with this study.

Image data acquired from the subjects will be analyzed by the principle investigator and by colleagues at Johns Hopkins University and the University of Florida. Regions of interest will be defined around pertinent target organs and tissues and the count data recorded. The specific target organs will depend on the particular radiopharmaceutical. The data for each age range and time point will be pooled, normalized and fit to models describing the pharmacokinetics. The resultant models will be evaluated for age-based variations in the PK data and compared to existing, published models based on adult data to evaluated age based differences. Lastly, the impact that the more accurate PK has on dosimetric estimates of patients of different ages will be analyzed.

The number of subjects required at each time point will be determined using nonlinear mixed effects modeling software to model the data and adjust for covariates. The likelihood ratio test based on the objective function value (OFV) will be used to estimate PK parameters for varying doses and ages using a Bayesian approach. The proposed sample size plan with subjects imaged at different time points is predicated on the Monte Carlo Mapped Power (MCMP) method to achieve 80% power for detecting age and dose effects and robust coverage in estimating individual PK parameters. It is expected that there will be 5-10 subjects per age group depending on the statistical requirements as described above.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Biokinetics Study for Tc-99m MDP for Dose Reduction in Pediatric Molecular Imaging
Actual Study Start Date : October 31, 2017
Actual Primary Completion Date : October 6, 2021
Actual Study Completion Date : October 6, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Tc-99m MDP
Patients ages 1-16 years old will be included. Routine SPECT imaging will be collected 3-4 h post-administration (PA) with a dual-detector rotating gamma camera over a 360˚ for 10-15 s per view using a 1282 matrix. Half of the subjects will also be imaged between 30 and 90 min, PA. The 2nd half will be at 4-6 h, PA. It is important to note that the patient volunteers will not receive any additional radiation exposure for inclusion in this study. They are only being ask to allow imaging at one additional time point.
Drug: Tc-99M MDP
Participants will be asked to be imaged at an additional time point during a nuclear medicine study using Tc-99m MDP

Other: Modification in acquisition protocol
Participants will be asked to be imaged at an additional time point.




Primary Outcome Measures :
  1. Radioactivity in target organs at various time points [ Time Frame: 6 hours ]
    The target-organ radioactivity measurements will be used to estimate the time-integrated activity in the target organs, hopefully leading to better estimates of absorbed dose to patients of different ages.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   9 Months to 16 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All patients within the specified age ranges scheduled at Boston Children's Hospital for a nuclear medicine study utilizing Tc-99m MDP will be eligible to volunteer for inclusion in this study. It is also essential that inclusion does not compromise the potential of acquiring the clinically indicated image acquisition.

Exclusion Criteria:

  • Inability to be imaged at the additional time point without the need for sedation or anesthesia

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03107247


Locations
Layout table for location information
United States, Massachusetts
Boston Children's Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Boston Children's Hospital
National Institute for Biomedical Imaging and Bioengineering (NIBIB)
Johns Hopkins University
University of Florida
Investigators
Layout table for investigator information
Principal Investigator: Frederic H Fahey, DSc Boston Children's Hospital
Publications:
Layout table for additonal information
Responsible Party: Frederic Fahey, Professor of Radiology, Boston Children's Hospital
ClinicalTrials.gov Identifier: NCT03107247    
Other Study ID Numbers: IRB-P00025086_2
First Posted: April 11, 2017    Key Record Dates
Last Update Posted: October 7, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Anonymized patient data, with all protected patient information removed, will be shared with collaborators at Johns Hopkins University and the University of Florida. In particular, anonymized nuclear medicine image data will be shared for analysis.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
Layout table for MeSH terms
Technetium Tc 99m Medronate
Radiopharmaceuticals
Molecular Mechanisms of Pharmacological Action