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

NCT ID: NCT03107247

Last Updated: 2022-12-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Total Enrollment

12 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-10-31

Study Completion Date

2021-10-06

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Skeletal Injury

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

OTHER

Study Time Perspective

OTHER

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Patients receiving Tc-99m MDP studies

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.

Imaging Time

Intervention Type DRUG

Participants will be asked to be imaged at an additional time point.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Imaging Time

Participants will be asked to be imaged at an additional time point.

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

9 Months

Maximum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Institute for Biomedical Imaging and Bioengineering (NIBIB)

NIH

Sponsor Role collaborator

Johns Hopkins University

OTHER

Sponsor Role collaborator

University of Florida

OTHER

Sponsor Role collaborator

Boston Children's Hospital

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Frederic Fahey

Professor of Radiology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Frederic H Fahey, DSc

Role: PRINCIPAL_INVESTIGATOR

Boston Children's Hospital

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

Fahey FH, Goodkind AB, Plyku D, Khamwan K, O'Reilly SE, Cao X, Frey EC, Li Y, Bolch WE, Sgouros G, Treves ST. Dose Estimation in Pediatric Nuclear Medicine. Semin Nucl Med. 2017 Mar;47(2):118-125. doi: 10.1053/j.semnuclmed.2016.10.006. Epub 2016 Nov 9.

Reference Type BACKGROUND
PMID: 28237000 (View on PubMed)

Treves ST, Gelfand MJ, Fahey FH, Parisi MT. 2016 Update of the North American Consensus Guidelines for Pediatric Administered Radiopharmaceutical Activities. J Nucl Med. 2016 Dec;57(12):15N-18N. No abstract available.

Reference Type BACKGROUND
PMID: 27909182 (View on PubMed)

O'Reilly SE, Plyku D, Sgouros G, Fahey FH, Ted Treves S, Frey EC, Bolch WE. A risk index for pediatric patients undergoing diagnostic imaging with (99m)Tc-dimercaptosuccinic acid that accounts for body habitus. Phys Med Biol. 2016 Mar 21;61(6):2319-32. doi: 10.1088/0031-9155/61/6/2319. Epub 2016 Mar 1.

Reference Type BACKGROUND
PMID: 26930549 (View on PubMed)

Sgouros G, Frey EC, Bolch WE, Wayson MB, Abadia AF, Treves ST. An approach for balancing diagnostic image quality with cancer risk: application to pediatric diagnostic imaging of 99mTc-dimercaptosuccinic acid. J Nucl Med. 2011 Dec;52(12):1923-9. doi: 10.2967/jnumed.111.092221.

Reference Type BACKGROUND
PMID: 22144506 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

IRB-P00025086_2

Identifier Type: -

Identifier Source: org_study_id