Renal DiseaseNCT03107195
Biokinetics Study of Tc-99m DMSA in Pediatric Molecular Imaging
An observational study of Renal Disease, run by Boston Children's Hospital at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 9 months to 6 years
- Conditions the study is for
- Renal Disease
- What is being tested?
- Imaging Time
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Oct 2017to 6 Oct 2021
- Phase
- Observational
- 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 9 months to 6 years
- All sexes
- No healthy volunteers
- Child
Study population: All patients within the specified age ranges scheduled at Boston Children's Hospital for a nuclear medicine study utilizing Tc-99m DMSA will be eligible to volunteer for inclusion in this study.
Who may be able to join
- All patients within the specified age ranges scheduled at Boston Children's Hospital for a nuclear medicine study utilizing Tc-99m DMSA 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.
Who cannot join
- Inability to be imaged at the additional time point without the need for sedation or anesthesia
Trial locations and contacts
1 site in 1 country.
United States1 site
Boston Children's Hospital
Boston, Massachusetts, 02115
About this study
Official title: Biokinetics Study of Tc-99m DMSA for Dose Reduction in Pediatric Molecular Imaging
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 4 radiopharmaceuticals 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 dimethylsuccinic acid (DMSA), 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.
Read the 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 4 radiopharmaceuticals 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 dimethylsuccinic acid (DMSA), a radiopharmaceutical commonly used in children for renal cortical 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 1-6 years old will be enrolled. Routine imaging will be performed 3-4 h post-administration (PA) with a dual-detector rotating gamma camera. In each age group, half of the subjects will also be imaged between 30 and 90 min, post-administration. The 2nd half will be imaged 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
- Renal Disease
- Being tested
- Imaging Time
- Medical subject headings
- Kidney Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Imaging TimeDrug
Participants will be asked to be imaged at an additional time point.
| Study group | Role | What they receive |
|---|---|---|
| Tc-99m DMSA | Patients aged 1-6 years old will be enrolled. Routine SPECT imaging will be performed 3-4 h post-administration (PA) with a dual-detector rotating gamma camera over a 360˚ rotation for 8 s per view using a 1282 matrix. In each age group, half of the subjects will also be imaged between 30 and 90 min, post-administration. The 2nd half will be imaged at 4-6 h, post-administration. 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. Receives: Drug: Imaging Time |
What is being measured
The primary outcome is the main question the study is designed to answer.
Radioactivity in target organs at various time points
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.
Measured: 6 hours
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 start31 Oct 2017
- Primary completion6 Oct 2021
- Study completion6 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Renal DiseaseStudies of the same condition, open and under way.
- More trials run by Boston Children's HospitalThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Other
- Time perspective
- Other
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute for Biomedical Imaging and Bioengineering (NIBIB), Johns Hopkins University, University of Florida
- Responsible party
- Principal investigator, Frederic Fahey, Boston Children's Hospital
- Investigators
- Frederic H Fahey, DSc, Principal investigator, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03107195
- Sponsor's protocol ID
- IRB-P00025086_1
- Status last verified
- Dec 2022
- First submitted
- 30 Mar 2017
- Last updated
- 12 Dec 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 28237000Treves 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.
PubMed 27909182Fahey FH, Ziniel SI, Manion D, Baker A, Treves ST. Administered Activities in Pediatric Nuclear Medicine and the Impact of the 2010 North American Consensus Guidelines on General Hospitals in the United States. J Nucl Med. 2016 Sep;57(9):1478-85. doi: 10.2967/jnumed.116.172148. Epub 2016 Apr 7.
PubMed 27056617O'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.
PubMed 26930549Sgouros 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.
PubMed 22144506
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biokinetics Study of Tc-99m DMSA for Dose Reduction in Pediatric Molecular Imaging
- ClinicalTrials.gov ID
- NCT03107195
- Acronym / sponsor ID
- IRB-P00025086_1
- Conditions
- Renal Disease
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Collaborators
- National Institute for Biomedical Imaging and Bioengineering (NIBIB), Johns Hopkins University, University of Florida
- Study start
- 31 Oct 2017 (actual)
- Primary completion
- 6 Oct 2021 (actual)
- Study completion
- 6 Oct 2021 (actual)
- 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 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 4 radiopharmaceuticals 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 dimethylsuccinic acid (DMSA), 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
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 4 radiopharmaceuticals 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 dimethylsuccinic acid (DMSA), a radiopharmaceutical commonly used in children for renal cortical 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 1-6 years old will be enrolled. Routine imaging will be performed 3-4 h post-administration (PA) with a dual-detector rotating gamma camera. In each age group, half of the subjects will also be imaged between 30 and 90 min, post-administration. The 2nd half will be imaged 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.
Study design
- Observational model
- Other
- Time perspective
- Other
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tc-99m DMSA | – | Drug: Imaging TimePatients aged 1-6 years old will be enrolled. Routine SPECT imaging will be performed 3-4 h post-administration (PA) with a dual-detector rotating gamma camera over a 360˚ rotation for 8 s per view using a 1282 matrix. In each age group, half of the subjects will also be imaged between 30 and 90 min, post-administration. The 2nd half will be imaged at 4-6 h, post-administration. 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. |
Who may qualify
- Ages
- 9 months to 6 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- All patients within the specified age ranges scheduled at Boston Children's Hospital for a nuclear medicine study utilizing Tc-99m DMSA will be eligible to volunteer for inclusion in this study.
Key inclusion criteria (1 listed)
- All patients within the specified age ranges scheduled at Boston Children's Hospital for a nuclear medicine study utilizing Tc-99m DMSA 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.
Key exclusion criteria (1 listed)
- Inability to be imaged at the additional time point without the need for sedation or anesthesia
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 |
|---|---|---|
| Imaging TimeParticipants will be asked to be imaged at an additional time point. | Drug | Tc-99m DMSA |
Primary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2022.
- Background: PubMed 28237000Fahey 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.
- Background: PubMed 27909182Treves 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.
- Background: PubMed 27056617Fahey FH, Ziniel SI, Manion D, Baker A, Treves ST. Administered Activities in Pediatric Nuclear Medicine and the Impact of the 2010 North American Consensus Guidelines on General Hospitals in the United States. J Nucl Med. 2016 Sep;57(9):1478-85. doi: 10.2967/jnumed.116.172148. Epub 2016 Apr 7.
- Background: PubMed 26930549O'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.
- Background: PubMed 22144506Sgouros 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.
- Individual participant dataSharing planned: Yes. 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.
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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.
Frederic H Fahey, DSc principal investigator
Boston Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Renal Disease, run by Boston Children's Hospital at 1 site in United States.
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 1 inclusion and 1 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: finished, as of the sponsor's last update on 12 Dec 2022. 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 United States. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Radioactivity in target organs at various time points (time frame: 6 hours). 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 NCT03107195, which also lists 5 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 Dec 2022.