Bone Diseases, DevelopmentalCOMBAT1NCT02617901
Developing a COMputerised Bone Age Tool
A study testing Left hand DXA in people with Bone Diseases, Developmental, run by Sheffield Children's NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
The Greulich and Pyle technique (G\&P) is that most commonly used to assess bone age in children, particularly in the context of suspected skeletal dysplasia. However it has been shown not to be applicable to children of Asian and African ethnicity and may not be applicable to United Kingdom (UK) Caucasian children… Read more about this study
- Who is it for?
- Ages 1 year to 16 years
- Conditions the study is for
- Bone Diseases, Developmental
- What is being tested?
- Left hand DXA
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Dec 2014to Apr 2016
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 1 year to 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Children having a left hand radiograph performed to assess bone age on the basis of clinical need
- Children and families who have given fully informed consent/assent
- Children and families capable of reading and/or writing English
Who cannot join
- 1. Participants who might not adequately understand verbal explanations or written information given in English, or who have special communication needs
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Sheffield Children's NHS Foundation Trust
Sheffield, Sheffield (South Yorkshire District), S10 2TH
About this study
Official title: COMBAT 1: COMputerised Bone Age Tool (Phase 1: Feasibility of Using Dual Energy X-ray Absorptiometry for Bone Age Assessment in Children)
The Greulich and Pyle technique (G\&P) is that most commonly used to assess bone age in children, particularly in the context of suspected skeletal dysplasia. However it has been shown not to be applicable to children of Asian and African ethnicity and may not be applicable to United Kingdom (UK) Caucasian children, who are now relatively more mature and larger than children of the mid 1930's (when G\&P was developed). It is generally agreed that updated standards are required for rapid and reliable bone age assessment. The development of such standards requires irradiation of normal children. To do this ethically, radiation exposure must be kept as low as possible. Two recent studies suggest that bone age assessment can be reliably achieved from dual-energy x-ray absorptiometry (DXA) scans. As far as the investigators are aware, the Tanner \& Whitehouse (TW3) method, which is preferred by some (e.g. endocrinologists and nutritionists), has not been assessed from dual-energy x-ray absorptiometry (DXA) scans - although not the main focus of this study, because of its popularity amongst certain specialties, the investigators shall be assessing the TW3 method also. Modern techniques should not only be available as textbooks, but should also be available in digital (on-line) format and where possible integrated with hospital PACS systems. The investigators believe that their team has the required experience and expertise to successfully carry out such a project. Before conducting the required large cross-sectional study, the investigators must first confirm that DXA can in fact replace radiographs for bone age assessment in children; which is the objective of this current study.
Read the detailed description
This is a small prospective feasibility study to be performed over a 12-month period.
Children booked for a left hand radiograph for bone age assessment (either in isolation or as part of a dysplasia skeletal survey) will be recruited. This will require a purposive sample of 2 males and 2 females from each of the following 5 age groups (<5; 5 to 7; 8 to 10; 11 to 13; 14 to 16 years). There will therefore be a total of 20 children (10 males). Because the aim of the study is to compare results of DXA with those of radiographs in corresponding children, ethnicity of individual children will not be an issue; in other words the investigators are assessing the reliability of DXA not the reliability of G\&P or TW3.
Relevant clinicians will identify patients from appropriate clinics at Sheffield Children's Hospital. Only patients having a left hand radiograph for bone age assessment on the basis of clinical need will be approached. Age appropriate information sheets will be given to them, and the study briefly discussed. When they arrive at the Radiology Department for their left hand radiograph, an appropriately certified radiographer will seek informed consent and provided the left hand radiograph is actually performed, they will then also have DXA of the left hand and those over 6 years old will be asked to complete a brief questionnaire.
Researcher 1 will anonymise hand radiographs and DXA scans, such that corresponding patient images are not identifiable. Researcher 1 will also document patient age and sex, ethnicity and body weight and height (no other clinical information is required for the purposes of this feasibility study).
Researchers 2, 3 and 4 will independently assess all images using both G\&P and TW3. All observers will interpret a random selection of half the images (again independently) on a second occasion at least 2 months after the first; on both occasions the Images will be interpreted in random and varied order. Images will be read in two batches of 10 radiographs and 10 (non-corresponding) DXA scans for the first read and 5 radiographs and 5 (non-corresponding) DXA scans for the second read.
Statistical analysis is largely irrelevant for this small feasibility study. The investigators' main aim is to assess whether or not G\&P and TW3 can be reliably assessed from hand DXA images.
The concordance between 1) independent readings of the three observers for radiographs and for DXA (i.e. comparing modalities) and 2) individual observers for both occasions (i.e. comparing observer reliability for each modality) will be evaluated using interclass and intraclass correlation coefficients. The investigators will calculate the mean and standard deviation of the differences between DXA and radiographs and between observers.
Statistical analyses will be performed using the Statistical Package for the Social Sciences, version 21 for Mac (SPSS, Chicago, IL).
- Conditions
- Bone Diseases, Developmental
- Being tested
- Left hand DXA
- Keywords
- Bone age, Greulich & Pyle, TW3, Radiography, Dual energy x-ray absorptiometry
- Medical subject headings
- Bone Diseases, Developmental
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Left hand DXARadiation
Also called DXA of left hand and wrist
All recruited children will have a left hand DXA scan which will be anonymised and from which 3 observers will independently assess bone age according to Greulich and Pyle and TW3 methods on 2 separate occasions at least 4 weeks apart.
Radiographs and DXA will be read in random and varied order.
| Study group | Role | What they receive |
|---|---|---|
| Recruited children | Experimental | Children aged below 16 years attending the Radiology Department for a left hand radiograph in order to assess bone age on the basis of clinical need. There will be one male and one female from each of five age groups (< 5 years; 5 to 7 years; 8 to 10 years; 11 to 13 years; 14 to 16 years).
Bone age will be assessed according to the Greulich \& Pyle and TW3 methods by 3 observers on 2 separate occasions at least 4 weeks apart. Recruited children will have intervention in the form of a left hand DXA which will be anonymised and from which the same 3 observers will independently assess bone age according to Greulich and Pyle and TW3 methods on 2 separate occasions at least 4 weeks apart.
Radiographs and DXA will be read in random and varied order. Receives: Radiation: Left hand DXA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Observer Agreement Between Bone Age as Assessed From Left Hand and Wrist DXA Compared to Radiographs
Bone age was assessed from DXA and conventional radiographs of the left hand and wrist based on the Greulich and Pyle and Tanner and Whitehouse methods of bone age assessment.
Interclass correlation was calculated to determine observer agreement between radiographs and DXA
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2015 (estimated)
- Study startDec 2014
- Primary completionApr 2016
- Study completionApr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Bone Diseases, DevelopmentalStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sheffield Children's NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- University of Sheffield
- Responsible party
- Sponsor
- Investigators
- Amaka Offiah, Principal investigator, Investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02617901
- Sponsor's protocol ID
- SCH/14/010
- Acronym
- COMBAT1
- Status last verified
- Jan 2020
- First submitted
- 23 Apr 2015
- Last updated
- 14 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Mora S, Boechat MI, Pietka E, Huang HK, Gilsanz V. Skeletal age determinations in children of European and African descent: applicability of the Greulich and Pyle standards. Pediatr Res. 2001 Nov;50(5):624-8. doi: 10.1203/00006450-200111000-00015.
PubMed 11641458van Rijn RR, Lequin MH, Robben SG, Hop WC, van Kuijk C. Is the Greulich and Pyle atlas still valid for Dutch Caucasian children today? Pediatr Radiol. 2001 Oct;31(10):748-52. doi: 10.1007/s002470100531.
PubMed 11685448Soudack M, Ben-Shlush A, Jacobson J, Raviv-Zilka L, Eshed I, Hamiel O. Bone age in the 21st century: is Greulich and Pyle's atlas accurate for Israeli children? Pediatr Radiol. 2012 Mar;42(3):343-8. doi: 10.1007/s00247-011-2302-1. Epub 2012 Jan 12.
PubMed 22237478
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- COMBAT 1: COMputerised Bone Age Tool (Phase 1: Feasibility of Using Dual Energy X-ray Absorptiometry for Bone Age Assessment in Children)
- ClinicalTrials.gov ID
- NCT02617901
- Acronym / sponsor ID
- COMBAT1 / SCH/14/010
- Conditions
- Bone Diseases, Developmental
- Keywords
- Bone age, Greulich & Pyle, TW3, Radiography, Dual energy x-ray absorptiometry
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Sheffield Children's NHS Foundation TrustUniversity, hospital or other
- Collaborators
- University of Sheffield
- Study start
- Dec 2014
- Primary completion
- Apr 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 1 Dec 2015 (estimated)
- Results
- Posted 13 Oct 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The Greulich and Pyle technique (G\&P) is that most commonly used to assess bone age in children, particularly in the context of suspected skeletal dysplasia. However it has been shown not to be applicable to children of Asian and African ethnicity and may not be applicable to United Kingdom (UK) Caucasian children, who are now relatively more mature and larger than children of the mid 1930's (when G\&P was developed). It is generally agreed that updated standards are required for rapid and reliable bone age assessment. The development of such standards requires irradiation of normal children. To do this ethically, radiation exposure must be kept as low as possible. Two recent studies suggest that bone age assessment can be reliably achieved from dual-energy x-ray absorptiometry (DXA) scans. As far as the investigators are aware, the Tanner \& Whitehouse (TW3) method, which is preferred by some (e.g. endocrinologists and nutritionists), has not been assessed from dual-energy x-ray absorptiometry (DXA) scans - although not the main focus of this study, because of its popularity amongst certain specialties, the investigators shall be assessing the TW3 method also. Modern techniques should not only be available as textbooks, but should also be available in digital (on-line) format and where possible integrated with hospital PACS systems. The investigators believe that their team has the required experience and expertise to successfully carry out such a project. Before conducting the required large cross-sectional study, the investigators must first confirm that DXA can in fact replace radiographs for bone age assessment in children; which is the objective of this current study.
Detailed description
This is a small prospective feasibility study to be performed over a 12-month period.
Children booked for a left hand radiograph for bone age assessment (either in isolation or as part of a dysplasia skeletal survey) will be recruited. This will require a purposive sample of 2 males and 2 females from each of the following 5 age groups (<5; 5 to 7; 8 to 10; 11 to 13; 14 to 16 years). There will therefore be a total of 20 children (10 males). Because the aim of the study is to compare results of DXA with those of radiographs in corresponding children, ethnicity of individual children will not be an issue; in other words the investigators are assessing the reliability of DXA not the reliability of G\&P or TW3.
Relevant clinicians will identify patients from appropriate clinics at Sheffield Children's Hospital. Only patients having a left hand radiograph for bone age assessment on the basis of clinical need will be approached. Age appropriate information sheets will be given to them, and the study briefly discussed. When they arrive at the Radiology Department for their left hand radiograph, an appropriately certified radiographer will seek informed consent and provided the left hand radiograph is actually performed, they will then also have DXA of the left hand and those over 6 years old will be asked to complete a brief questionnaire.
Researcher 1 will anonymise hand radiographs and DXA scans, such that corresponding patient images are not identifiable. Researcher 1 will also document patient age and sex, ethnicity and body weight and height (no other clinical information is required for the purposes of this feasibility study).
Researchers 2, 3 and 4 will independently assess all images using both G\&P and TW3. All observers will interpret a random selection of half the images (again independently) on a second occasion at least 2 months after the first; on both occasions the Images will be interpreted in random and varied order. Images will be read in two batches of 10 radiographs and 10 (non-corresponding) DXA scans for the first read and 5 radiographs and 5 (non-corresponding) DXA scans for the second read.
Statistical analysis is largely irrelevant for this small feasibility study. The investigators' main aim is to assess whether or not G\&P and TW3 can be reliably assessed from hand DXA images.
The concordance between 1) independent readings of the three observers for radiographs and for DXA (i.e. comparing modalities) and 2) individual observers for both occasions (i.e. comparing observer reliability for each modality) will be evaluated using interclass and intraclass correlation coefficients. The investigators will calculate the mean and standard deviation of the differences between DXA and radiographs and between observers.
Statistical analyses will be performed using the Statistical Package for the Social Sciences, version 21 for Mac (SPSS, Chicago, IL).
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Recruited children | Experimental | Radiation: Left hand DXAChildren aged below 16 years attending the Radiology Department for a left hand radiograph in order to assess bone age on the basis of clinical need. There will be one male and one female from each of five age groups (< 5 years; 5 to 7 years; 8 to 10 years; 11 to 13 years; 14 to 16 years). Bone age will be assessed according to the Greulich \& Pyle and TW3 methods by 3 observers on 2 separate occasions at least 4 weeks apart. Recruited children will have intervention in the form of a left hand DXA which will be anonymised and from which the same 3 observers will independently assess bone age according to Greulich and Pyle and TW3 methods on 2 separate occasions at least 4 weeks apart. Radiographs and DXA will be read in random and varied order. |
Who may qualify
- Ages
- 1 year to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Children having a left hand radiograph performed to assess bone age on the basis of clinical need
- Children and families who have given fully informed consent/assent
- Children and families capable of reading and/or writing English
Key exclusion criteria (1 listed)
- 1. Participants who might not adequately understand verbal explanations or written information given in English, or who have special communication needs
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 |
|---|---|---|
| Left hand DXAAlso: DXA of left hand and wristAll recruited children will have a left hand DXA scan which will be anonymised and from which 3 observers will independently assess bone age according to Greulich and Pyle and TW3 methods on 2 separate occasions at least 4 weeks apart. Radiographs and DXA will be read in random and varied order. | Radiation | Recruited children |
Primary outcome
Number of Participants With Observer Agreement Between Bone Age as Assessed From Left Hand and Wrist DXA Compared to Radiographs
Time frame: 18 months
Bone age was assessed from DXA and conventional radiographs of the left hand and wrist based on the Greulich and Pyle and Tanner and Whitehouse methods of bone age assessment. Interclass correlation was calculated to determine observer agreement between radiographs and DXA
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 11641458Mora S, Boechat MI, Pietka E, Huang HK, Gilsanz V. Skeletal age determinations in children of European and African descent: applicability of the Greulich and Pyle standards. Pediatr Res. 2001 Nov;50(5):624-8. doi: 10.1203/00006450-200111000-00015.
- Background: PubMed 11685448van Rijn RR, Lequin MH, Robben SG, Hop WC, van Kuijk C. Is the Greulich and Pyle atlas still valid for Dutch Caucasian children today? Pediatr Radiol. 2001 Oct;31(10):748-52. doi: 10.1007/s002470100531.
- Background: PubMed 22237478Soudack M, Ben-Shlush A, Jacobson J, Raviv-Zilka L, Eshed I, Hamiel O. Bone age in the 21st century: is Greulich and Pyle's atlas accurate for Israeli children? Pediatr Radiol. 2012 Mar;42(3):343-8. doi: 10.1007/s00247-011-2302-1. Epub 2012 Jan 12.
- Individual participant dataSharing planned: No
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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.
Amaka Offiah principal investigator
Investigator
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Left hand DXA in people with Bone Diseases, Developmental, run by Sheffield Children's NHS Foundation Trust at 1 site in United Kingdom.
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 3 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 14 Jan 2020. 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 Kingdom. 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?
Yes. Results are posted in the registry (first posted 13 Oct 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Observer Agreement Between Bone Age as Assessed From Left Hand and Wrist DXA Compared to Radiographs (time frame: 18 months). 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 NCT02617901, which also lists 3 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 14 Jan 2020.