Clinical trial NCT02814591: Development of a Non-invasive Assessment of Human Bone Quality Using Spatially Offset Raman Spectroscopy
Official title: Development of a Novel, Safe Method for the Non-invasive Assessment of Human Bone Quality, In Vivo, Using Spatially Offset Raman Spectroscopy
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Osteoarthritis
Osteoporosis
Osteogenesis Imperfecta
Rickets / Osteomalacia
Bone Infection
Lead sponsor: University College, London
Sponsor class: OTHER
Collaborators: name: Royal National Orthopaedic Hospital NHS Trust
name: Science & Technology Facilities Council
First posted: 2016-06-28
Enrollment: 245
Sex: ALL
Minimum age (years): 0
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Control patients, patients with osteoarthritis, patients with osteoporosis, patients with osteogenesis imperfecta, patients with rickets or osteomalacia, patients with suspected bone infection.

Brief summary: In this study spatially offset Raman spectroscopy (SORS), which allows the collection of Raman spectra through turbid media, is being applied to collect Raman spectra of bone. The principal aim to find ways to use Raman spectroscopy to assess bone quality in vivo.


Eligibility criteria: INCLUSION CRITERIA

Cohort 1: 40 volunteers, free from bone disease:

* Participants must be free from bone disease and not have a family history of OI;
* Participants to be age and sex matched with OP participants may be recruited among individuals attending the RNOH Metabolic Unit for DXA scanning, who are shown to have normal bone density T score\> -2.5;
* No history of non-accidental fracture;
* No history of OA or clinical manifestations of disease;
* No clinical features of OI;
* Controls will be sex and age matched (within five years) to the disease cohort patients.
* Children and adults both required

Cohort 2: 40 patients with OI:

* Patients must have been clinically diagnosed with OI;
* Where possible participants will be identified from the Royal National Orthopaedic Hospital, Metabolic Unit database; if not from RNOH then diagnosis will be otherwise confirmed

Cohort 3: 40 patients with OA:

* Patients must have been clinically diagnosed with OA;
* Participants will be identified from the Royal National Orthopaedic Hospital, Metabolic Unit database; if not from RNOH then diagnosis will be otherwise confirmed

Cohort 4: 40 patients with OI, receiving treatment with bisphosphonates:

* Patients must have been clinically diagnosed with OI and bisphosphonates prescribed as a course of treatment;
* 20 Adults and 20 children
* Where possible participants will be identified from the Royal National Orthopaedic Hospital, Metabolic Unit database; if not from RNOH then diagnosis will be otherwise confirmed
* Where possible measurements will be acquired prior to the start of treatment and then for up to 4 follow up visits at flexible time points to allow scheduling to coincide with hospital appointments. The minimum time between visits should be 2 months.

Cohort 5: 2x 30 patients with OP (two treatment groups):

* Patients must have been clinically diagnosed with OP;
* The first cohort will have been prescribed with bisphosphonate anti-resorptive treatment; the second with anabolic agents. Where treatment has ceased but remains active (long-acting), potential participants may be included at Dr. Keen's discretion.
* Where possible participants will be identified from the Royal National Orthopaedic Hospital, Metabolic Unit database; if not from RNOH then diagnosis will be otherwise confirmed
* BMD confirmed with DXA
* Where possible measurements will be acquired prior to the start of treatment and then up to 4 follow up visits at flexible time points to allow scheduling to coincide with hospital appointments. Minimum time between visits should be 2 months.

Cohort 6: 10-15 participants with rickets, 10-15 participants with osteomalacia

* Patients must have been clinically diagnosed with rickets/osteomalacia;
* Blood tests for 25-hydroxyvitamin D should be ≤25 nmol/L
* Once participants are on treatment a further measurement will be made 6 months afterwards
* Participants for rickets and osteomalacia groups will be recruited to give a total of 10 complete sets of data per group

Cohort 7: 5 participants with a suspected bone infection

* Participants will have been diagnosed at RNOH with a suspected bone infection
* Participants will be scanned around the localised area of suspected infection. Measurements may also be taken away from the infection on the same side and the contralateral anatomical location e.g., if infection is suspected at the right knee then we may also scan further down the right leg and the left leg.
* Participants may have 1 or 2 visits; the latter to take place after all infection has cleared up. This is not subject to a fixed time frame.

EXCLUSION CRITERIA In general smokers will be excluded. Ex-smokers will be included only if they gave up smoking a minimum of 5 years ago.

Cohort 1: 40 volunteers, free from bone disease:

* A participant with a history of bone disease or non-accidental fracture
* Clinical features of bone disease

Cohort 2: 40 patients with OI; Cohort 3: 40 patients with OA; Cohort 6: 20 patients with rickets/osteomalacia • Patients with more than 1 type of bone disease

Cohorts 4, 5 and 6: receiving treatment

• Patients who have been advised to stop treatment. If the treatment is a long-acting one (i.e., will remain effective in the body) then the participant may be included.

Primary outcomes:
measure: SORS Raman spectral fingerprint for bone disease types and changes over time
timeFrame: SORS Raman spectral features will be evaluated using a variety of multi-variate analytical tools e.g. BTEM at time zero and a repeat measure within a year.
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: UCL
name: Helen Birch, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Royal National Orthopaedic Hospital NHS Trust (RNOH)
name: Panos Gikas, Consultant Rheumatologist
role: PRINCIPAL_INVESTIGATOR
References: