OsteoarthritisMetal IonsNCT01493141
Systemic Effects of Chronic Metal Ion Exposure From Metal-on Metal Hip Resurfacing
An observational study of Osteoarthritis, run by Sheffield Teaching Hospitals NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
In recent years hip resurfacing has become a very popular alternative treatment to total hip replacement for the treatment of hip arthritis. This procedure has become particularly common in the young patient with arthritis because of perceived benefits in terms of functional outcome. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Osteoarthritis
- How many people
- 46 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Nov 2009to Apr 2012
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: All potential subjects will be identified from the clinical records and registered databases of Mr Wilkinson and Mr Stockley, who are the clinicians who have been directly responsible for the patients clinical care with respect to their hip arthritis.
Who may be able to join
- MOMHR subjects - 35 Men and women at a minimum of 5 years following unilateral or bilateral MOMHR for primary or secondary OA
- Conventional THA subjects - These subjects will be individually (casebycase) matched with MOMHR subjects for age (±3 years), sex, and year of primary arthroplasty surgery (±2 years).
Who cannot join
- Known inflammatory arthropathy or metabolic bone disease.
- Use of pharmacological doses of estrogen, progestin, androgen, calcitonin, glucocorticoids, or dietary supplements of calcium or vitamin D within the previous 12 months
- Any previous use of bisphosphonate or fluoride therapy (excluding dental prophylaxis)
- Pregnancy
- Subjects who cannot undergo an MRI scan for medical reasons e.g. those with a cardiac pacemaker
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Sheffield Teaching Hospitals NHS Foundation Trust
Sheffield, South Yorkshire, S5 7AU
About this study
In recent years hip resurfacing has become a very popular alternative treatment to total hip replacement for the treatment of hip arthritis. This procedure has become particularly common in the young patient with arthritis because of perceived benefits in terms of functional outcome. However, it has recently become apparent that hip resurfacing is associated with a range of adverse events, not typically seen in patients with conventional hip replacement. These include hip fracture, and failure of bone to grow onto the fixation surfaces of the implant. It has also become apparent that hip resurfacing results in the release of high concentrations of dissolved metals in the bloodstream, such as cobalt and chromium. Whilst small concentrations of these metals are essential for normal body functions, such as making red blood cells, in high concentrations their effects can be toxic to many cells and organs of the body, such as bone, the brain, heart, liver and kidneys, as well as disturbing hormones and blood cholesterol levels. Whilst several studies have documented levels of these metal ions of 440 times normal levels in hip resurfacing patients, there are no studies that have examined whether these levels are having a toxic effect on the various organ systems of the body (with the exception of renal function). In this study we plan to explore whether there are differences in bone mineral density, accumulation of metal ions in the brain, and other solid organs, heart and hormonal function between subjects who have had a hip resurfacing 5 or more years previously compared to an individually matched group of subjects after conventional hip replacement.
Read the detailed description
This is a cross sectional survey in patients who have had hip resurfacing (MOMHR) and subjects who have received a conventional hip replacement (THA) using a metal on plastic or ceramic bearing. Participants in this study will be identified by orthopaedic surgeons from their operating database. An invitation letter will be sent out to the potential participants with an accompanying information sheet and a reply slip. If there is no response then one further letter will be sent out. Those patients who respond to say that they are interested in taking part in the study will then be telephoned by the study team and screened for inclusion/exclusion criteria. If they are eligible and willing to take part after discussions with the investigator, an appointment will be made for them to attend to give informed consent. Participants will be requested not to eat or drink on the morning that they attend for this visit.
There will be an opportunity at this visit for further discussion and explanation of the study requirements with the Investigator before consent is given.
Once consent has been given, the following procedures will be carried out at this visit (Visit 1):
- Venous blood will be taken by venepuncture (60 mL, approx 4 tablespoons, will be taken) after which the participant will be able to eat breakfast (which will be provided).
- A urine based pregnancy test will be used in women of child bearing age to exclude pregnant women
- Participants will complete the Oxford Hip questionnaire, the EQ5D questionnaire and a record of medical history and concomitant medicines under supervision of the student investigator or an experienced research nurse.
- Whole body bone mineral density assessments will be made using an Hologic Discovery bone densitometer. This will take approximately 10 minutes in total and will be carried out by an experienced research bone density technician
- An electrocardiogram and an echocardiogram will be performed by an experienced cardiotechnician and later analysed by a Consultant Cardiologist
- Participants will be given a container and instructions to collect a 24 hour urine sample. This will be returned at the second visit
- An appointment will be made for the participant to attend for a second visit to the Royal Hallamshire Hospital.
At visit 2 the following procedures will be carried out:
- Neuropsychological assessments and questionnaires and visual acuity measurement using a Snellen chart.
- Magnetic resonance imaging (MRI) of the brain using a 3.0T Phillips Intera MRI scanner.
- MRI of the liver spleen and kidneys using the 3.0T Phillips Intera MRI scanner. Clinical reports will be prepared for all clinical investigations and normal findings will be related to the patient by letter.
Abnormal findings will be reported to the GP and patient with advice for any action as necessary.
- Conditions
- Osteoarthritis
- Keywords
- MOMHR, THA, Osteoarthritis
- Medical subject headings
- Osteoarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| MOMHR | Patients who have had metal-on metal hip resurfacing (MOMHR) | |
| THA | Patients who have had metal-on-polyethylene or ceramic total hip arthroplasty (THA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in whole body bone mineral density measured by DXA between patients with MOMHR compared to conventional hip arthroplasty
Measured: >5 years after procedure
Secondary outcomes (11)
Serum and urine biochemical markers of osteoclast and osteoblast activity.
Measured: >5 years after procedure
Serum, erythrocyte, and whole blood cobalt and chromium levels, measured by inductively-coupled plasma mass spectrometry (ICP MS)
Measured: >5 years after procedure
24 hour urinary excretion of cobalt and chromium, measured by ICP MS
Measured: >5 years after procedure
Metal ion deposition in solid organs including the brain, liver and kidneys identified by MRI
Measured: >5 years after procedure
Cognitive function and visual acuity
Measured: >5 years after procedure
Cardiac function, measured by transthoracic echocardiography and electrocardiogram
Measured: >5 years after procedure
Renal function measured by serum creatinine, urinary creatinine clearance, urinary N-acetyl-β-D-glucosaminidase (NAG) and Kidney Injury Molecule-1 (Kim-1)
Measured: >5 years after procedure
Hepatic function measured by liver function tests and clotting screen
Measured: >5 years after procedure
Endocrine function measured by assessment of hypathalamo-pituitary axis hormones
Measured: >5 years after procedure
Serum lipid profile and polycythemia, measured by serum triglycerides, cholesterol, and full blood count
Measured: >5 years after procedure
Clinical hip replacement function measured by Oxford hip score and EQ-5D
Measured: >5 years after procedure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2011 (estimated)
- Study startNov 2009
- Primary completionApr 2012
- Study completionApr 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for OsteoarthritisStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sheffield Teaching Hospitals NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- University of Sheffield
- Responsible party
- Sponsor
- Investigators
- Mark JM Wilkinson, Prof, Principal investigator, University of Sheffield
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01493141
- Sponsor's protocol ID
- STH15402
- Acronym
- Metal Ions
- Status last verified
- Dec 2012
- First submitted
- 7 Dec 2011
- Last updated
- 17 Dec 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Systemic Effects of Chronic Metal Ion Exposure From Metal-on Metal Hip Resurfacing
- ClinicalTrials.gov ID
- NCT01493141
- Acronym / sponsor ID
- Metal Ions / STH15402
- Conditions
- Osteoarthritis
- Keywords
- MOMHR, THA, Osteoarthritis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Sheffield Teaching Hospitals NHS Foundation TrustUniversity, hospital or other
- Collaborators
- University of Sheffield
- Study start
- Nov 2009
- Primary completion
- Apr 2012 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 15 Dec 2011 (estimated)
- 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.
In recent years hip resurfacing has become a very popular alternative treatment to total hip replacement for the treatment of hip arthritis. This procedure has become particularly common in the young patient with arthritis because of perceived benefits in terms of functional outcome. However, it has recently become apparent that hip resurfacing is associated with a range of adverse events, not typically seen in patients with conventional hip replacement. These include hip fracture, and failure of bone to grow onto the fixation surfaces of the implant. It has also become apparent that hip resurfacing results in the release of high concentrations of dissolved metals in the bloodstream, such as cobalt and chromium. Whilst small concentrations of these metals are essential for normal body functions, such as making red blood cells, in high concentrations their effects can be toxic to many cells and organs of the body, such as bone, the brain, heart, liver and kidneys, as well as disturbing hormones and blood cholesterol levels. Whilst several studies have documented levels of these metal ions of 440 times normal levels in hip resurfacing patients, there are no studies that have examined whether these levels are having a toxic effect on the various organ systems of the body (with the exception of renal function). In this study we plan to explore whether there are differences in bone mineral density, accumulation of metal ions in the brain, and other solid organs, heart and hormonal function between subjects who have had a hip resurfacing 5 or more years previously compared to an individually matched group of subjects after conventional hip replacement.
Detailed description
This is a cross sectional survey in patients who have had hip resurfacing (MOMHR) and subjects who have received a conventional hip replacement (THA) using a metal on plastic or ceramic bearing. Participants in this study will be identified by orthopaedic surgeons from their operating database. An invitation letter will be sent out to the potential participants with an accompanying information sheet and a reply slip. If there is no response then one further letter will be sent out. Those patients who respond to say that they are interested in taking part in the study will then be telephoned by the study team and screened for inclusion/exclusion criteria. If they are eligible and willing to take part after discussions with the investigator, an appointment will be made for them to attend to give informed consent. Participants will be requested not to eat or drink on the morning that they attend for this visit.
There will be an opportunity at this visit for further discussion and explanation of the study requirements with the Investigator before consent is given.
Once consent has been given, the following procedures will be carried out at this visit (Visit 1):
- Venous blood will be taken by venepuncture (60 mL, approx 4 tablespoons, will be taken) after which the participant will be able to eat breakfast (which will be provided).
- A urine based pregnancy test will be used in women of child bearing age to exclude pregnant women
- Participants will complete the Oxford Hip questionnaire, the EQ5D questionnaire and a record of medical history and concomitant medicines under supervision of the student investigator or an experienced research nurse.
- Whole body bone mineral density assessments will be made using an Hologic Discovery bone densitometer. This will take approximately 10 minutes in total and will be carried out by an experienced research bone density technician
- An electrocardiogram and an echocardiogram will be performed by an experienced cardiotechnician and later analysed by a Consultant Cardiologist
- Participants will be given a container and instructions to collect a 24 hour urine sample. This will be returned at the second visit
- An appointment will be made for the participant to attend for a second visit to the Royal Hallamshire Hospital.
At visit 2 the following procedures will be carried out:
- Neuropsychological assessments and questionnaires and visual acuity measurement using a Snellen chart.
- Magnetic resonance imaging (MRI) of the brain using a 3.0T Phillips Intera MRI scanner.
- MRI of the liver spleen and kidneys using the 3.0T Phillips Intera MRI scanner. Clinical reports will be prepared for all clinical investigations and normal findings will be related to the patient by letter.
Abnormal findings will be reported to the GP and patient with advice for any action as necessary.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MOMHR | – | –Patients who have had metal-on metal hip resurfacing (MOMHR) |
| THA | – | –Patients who have had metal-on-polyethylene or ceramic total hip arthroplasty (THA) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All potential subjects will be identified from the clinical records and registered databases of Mr Wilkinson and Mr Stockley, who are the clinicians who have been directly responsible for the patients clinical care with respect to their hip arthritis.
Key inclusion criteria (2 listed)
- MOMHR subjects - 35 Men and women at a minimum of 5 years following unilateral or bilateral MOMHR for primary or secondary OA
- Conventional THA subjects - These subjects will be individually (casebycase) matched with MOMHR subjects for age (±3 years), sex, and year of primary arthroplasty surgery (±2 years).
Key exclusion criteria (5 listed)
- Known inflammatory arthropathy or metabolic bone disease.
- Use of pharmacological doses of estrogen, progestin, androgen, calcitonin, glucocorticoids, or dietary supplements of calcium or vitamin D within the previous 12 months
- Any previous use of bisphosphonate or fluoride therapy (excluding dental prophylaxis)
- Pregnancy
- Subjects who cannot undergo an MRI scan for medical reasons e.g. those with a cardiac pacemaker
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Difference in whole body bone mineral density measured by DXA between patients with MOMHR compared to conventional hip arthroplasty
Time frame: >5 years after procedure
11 secondary outcomes
Serum and urine biochemical markers of osteoclast and osteoblast activity.
Time frame: >5 years after procedure
Serum, erythrocyte, and whole blood cobalt and chromium levels, measured by inductively-coupled plasma mass spectrometry (ICP MS)
Time frame: >5 years after procedure
24 hour urinary excretion of cobalt and chromium, measured by ICP MS
Time frame: >5 years after procedure
Metal ion deposition in solid organs including the brain, liver and kidneys identified by MRI
Time frame: >5 years after procedure
Cognitive function and visual acuity
Time frame: >5 years after procedure
Cardiac function, measured by transthoracic echocardiography and electrocardiogram
Time frame: >5 years after procedure
Renal function measured by serum creatinine, urinary creatinine clearance, urinary N-acetyl-β-D-glucosaminidase (NAG) and Kidney Injury Molecule-1 (Kim-1)
Time frame: >5 years after procedure
Hepatic function measured by liver function tests and clotting screen
Time frame: >5 years after procedure
Endocrine function measured by assessment of hypathalamo-pituitary axis hormones
Time frame: >5 years after procedure
Serum lipid profile and polycythemia, measured by serum triglycerides, cholesterol, and full blood count
Time frame: >5 years after procedure
Clinical hip replacement function measured by Oxford hip score and EQ-5D
Time frame: >5 years after procedure
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 17 Dec 2012.
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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.
Mark JM Wilkinson, Prof principal investigator
University of Sheffield
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 Osteoarthritis, run by Sheffield Teaching Hospitals 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 2 inclusion and 5 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 17 Dec 2012. 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?
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?
Difference in whole body bone mineral density measured by DXA between patients with MOMHR compared to conventional hip arthroplasty (time frame: >5 years after procedure). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Dec 2012.