Systemic Effects of Chronic Metal Ion Exposure From Metal-on Metal Hip Resurfacing (Metal Ions)

This study has been completed.
Sponsor:
Collaborator:
University of Sheffield
Information provided by (Responsible Party):
Sheffield Teaching Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01493141
First received: December 7, 2011
Last updated: December 14, 2012
Last verified: December 2012

December 7, 2011
December 14, 2012
November 2009
April 2012   (final data collection date for 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 ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01493141 on ClinicalTrials.gov Archive Site
  • Serum and urine biochemical markers of osteoclast and osteoblast activity. [ Time Frame: >5 years after procedure ] [ Designated as safety issue: No ]
  • Serum, erythrocyte, and whole blood cobalt and chromium levels, measured by inductively-coupled plasma mass spectrometry (ICP MS) [ Time Frame: >5 years after procedure ] [ Designated as safety issue: No ]
  • 24 hour urinary excretion of cobalt and chromium, measured by ICP MS [ Time Frame: >5 years after procedure ] [ Designated as safety issue: No ]
  • Metal ion deposition in solid organs including the brain, liver and kidneys identified by MRI [ Time Frame: >5 years after procedure ] [ Designated as safety issue: No ]
  • Cognitive function and visual acuity [ Time Frame: >5 years after procedure ] [ Designated as safety issue: No ]
  • Cardiac function, measured by transthoracic echocardiography and electrocardiogram [ Time Frame: >5 years after procedure ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Hepatic function measured by liver function tests and clotting screen [ Time Frame: >5 years after procedure ] [ Designated as safety issue: No ]
  • Endocrine function measured by assessment of hypathalamo-pituitary axis hormones [ Time Frame: >5 years after procedure ] [ Designated as safety issue: No ]
  • Serum lipid profile and polycythemia, measured by serum triglycerides, cholesterol, and full blood count [ Time Frame: >5 years after procedure ] [ Designated as safety issue: No ]
  • Clinical hip replacement function measured by Oxford hip score and EQ-5D [ Time Frame: >5 years after procedure ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Systemic Effects of Chronic Metal Ion Exposure From Metal-on Metal Hip Resurfacing
Systemic Effects of Chronic Metal Ion Exposure From Metal-on Metal Hip Resurfacing

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.

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):

  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).
  2. A urine based pregnancy test will be used in women of child bearing age to exclude pregnant women
  3. 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.
  4. 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
  5. An electrocardiogram and an echocardiogram will be performed by an experienced cardiotechnician and later analysed by a Consultant Cardiologist
  6. Participants will be given a container and instructions to collect a 24 hour urine sample. This will be returned at the second visit
  7. 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:

  1. Neuropsychological assessments and questionnaires and visual acuity measurement using a Snellen chart.
  2. Magnetic resonance imaging (MRI) of the brain using a 3.0T Phillips Intera MRI scanner.
  3. 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.

Observational
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:

The following markers will be measured using the blood samples:

  1. Serum, erythrocyte, and whole blood cobalt, chromium, and nickel
  2. Serum iron stores:

    Iron, ferritin, transferrin, and total iron binding capacity.

  3. Serum biochemical markers of bone turnover:

    Osteoblast activity markers (including PINP, OC, BALP) Osteoclast activity markers (including NTX-I, CTX-I, ICTP)

  4. Hypothalamo-pituitary axis hormones (in the following order of priority):

    Prolactin LH/FSH + testosterone/oestradiol Growth hormone + IGF-I TSH + Free T3 ACTH + cortisol

  5. Renal function:

    Urea, electrolytes, and creatinine

  6. Hepatic function Liver function tests Clotting screen
  7. Serum lipid profile, full blood count
Non-Probability Sample

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.

Osteoarthritis
Not Provided
  • 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)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
46
April 2012
April 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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).

Exclusion Criteria:

  • 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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United Kingdom
 
NCT01493141
STH15402
No
Sheffield Teaching Hospitals NHS Foundation Trust
Sheffield Teaching Hospitals NHS Foundation Trust
University of Sheffield
Principal Investigator: Mark JM Wilkinson, Prof University of Sheffield
Sheffield Teaching Hospitals NHS Foundation Trust
December 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP