Clinical trial NCT03429426: Progression of Bone Erosions in Rheumatoid Arthritis Assessed by HR-pQCT and Conventional X-ray
Official title: An Observational Study of Bone Erosion Determination and Progression in Rheumatoid Arthritis Assessed by HR-pQCT and Conventional X-ray
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Arthritis, Rheumatoid
Keywords: Rheumatoid Arthritis
High-resolution peripheral quantitative computed tomography
Radiography
Lead sponsor: Aarhus University Hospital
Sponsor class: OTHER
Collaborators: name: University of Aarhus
First posted: 2018-02-12
Enrollment: 625
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Rheumatoid arthritis patients and pre-rheumatoid patients are recruited from the outpatient clinic at the Department of Rheumatology, Aarhus University Hospital.

Healthy age- and sex-matched Individuals are recruited, as a control group, by posting at libraries in Aarhus, Aarhus University, Aarhus University Hospital and postings on the websites www.forsøgsperson.dk and www.Sundhed.dk.

Brief summary: Today, regular X-ray examination is not sufficiently sensitive for detecting progression of bone destruction in rheumatoid arthritis, but a new type of high-resolution CT scanner, the High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT) can detect very early and minor joint injuries.

The purpose of this study is to use HR-pQCT techniques to look at the damage and disease activity progression in the hand and wrist joints of patients with rheumatoid arthritis.

Detailed description: The design of the trial is an observational study with three distinct groups. At the start of the trial period and at one-year of follow-up, the trial subject will have their hand X-rayed by conventional radiography, and their metacarpophalangeal (MCP) joint and wrist scanned by HR-pQCT-Imaging. The 28-joint Disease Activity Score(DAS28-CRP), Health Assessment Questionnaire (HAQ), Visual analogue scale(VAS)-score for pain, fatigue and quality of life are performed to investigate the correlation between radiographic changes and disease activity. Blood samples are collected to investigate serological markers of bone metabolism and inflammation and the radiographic changes. The following groups are investigated:

* Rheumatoid Arthritis(RA): Patients with RA ≥5 years according to the ACR/EULAR 2010 classification criteria or the American Rheumatism Association 1987 revised criteria are recruited from the outpatient clinic at the Department of Rheumatology, Aarhus University Hospital. Treatment will be adjusted according to the patient's need and according to national guidelines. (n=450)
* Pre-RA patients: Patients with pre-RA, (joint pain, but no swelling and Anti-CCP 3 times above the upper limit) are recruited from the outpatient clinic at the Department of Rheumatology, Aarhus University Hospital. (n=75)
* Healthy subjects: Healthy age- and sex-matched Individuals are recruited, as a control group, by posting at libraries in Aarhus, Aarhus University, Aarhus University Hospital and postings on the websites www.forsøgsperson.dk and www.Sundhed.dk. (N=100)

Eligibility criteria: Rheumatoid arthritis patients Inclusion criteria

* Patients (\> 18 years) with rheumatoid arthritis ≥5 years according to the ACR/EULAR (2010) classification criteria or American Rheumatism Association 1987 revised criteria for the patients who were diagnosed before 2010.
* Patients who are receiving treatment on an outpatient basis.
* Ability and willingness to give written informed consent and to meet the requirements of the trial protocol.

Exclusion criteria

* Patients who have previously suffered trauma in the form of fracture or luxation of the hand are excluded.
* Evidence of active malignant disease.
* Hypo- or hyperthyroidism.
* Hypocalcaemia.
* Impaired renal function (eGFR \<35ml/min).
* Pregnancy. Pre-rheumatoid arthritis patients Inclusion criteria
* Age over 18 years.
* Anti-CCP 3 times the upper limit of the reference interval.
* Arthralgia.
* Ability and willingness to give written informed consent and to meet the requirements of the trial protocol.

Exclusion criteria

* Pregnancy.
* Swelling of joints. Verified by clinical ultrasound.
* Patients who have previously suffered trauma in the form of fracture or luxation of the hand are excluded.
* Evidence of malignant disease.
* Hypo- or hyperthyroidism.
* Hypocalcaemia. Healthy subjects Inclusion criteria
* Age over 18 years.
* No joint complaints.
* Ability and willingness to give written informed consent and to meet the requirements of the trial protocol.

Exclusion criteria

* Patients who have previously suffered trauma in the form of fracture or luxation of the hand are excluded.
* Evidence of malignant disease.
* Hypo- or hyperthyroidism.
* Hypocalcaemia.
* Impaired renal function (eGFR \<35ml/min).
* Earlier or present rheumatological disease or bone metabolic disease.
* Positive anti-CCP.
* Pregnancy.

Primary outcomes:
measure: Erosion changes by HR-pQCT
timeFrame: One year
measure: Volumetric bone mineral density(vBMD) changes by HR-pQCT
timeFrame: One year
measure: Erosion changes by HR-pQCT
timeFrame: One year
measure: Erosion changes by HR-pQCT
timeFrame: One year
Secondary outcomes:
measure: Radiographic erosion score
timeFrame: One year
measure: CTX
timeFrame: one year
measure: P1NP
timeFrame: one year
measure: BAP
timeFrame: one year
measure: TNF-α
timeFrame: one year
measure: RANK-L
timeFrame: one year
measure: OPG
timeFrame: one year
measure: BGLAP
timeFrame: one year
measure: SCL
timeFrame: one year
measure: Dkk-1
timeFrame: one year
measure: IL-1
timeFrame: one year
measure: IL-6
timeFrame: one year
measure: IL-15
timeFrame: one year
measure: IL-16
timeFrame: one year
measure: IL-17
timeFrame: one year
measure: IL-22
timeFrame: one year
measure: IL-33
timeFrame: one year
measure: CCL11
timeFrame: one year
measure: CXCL13
timeFrame: one year
measure: TRACP 5b
timeFrame: one year
measure: CRP
timeFrame: one year
measure: Disease Activity Score
timeFrame: one year
measure: Health Assessment Questionnaire
timeFrame: one year
measure: VAS for pain
timeFrame: one year
measure: VAS for fatigue
timeFrame: one year
measure: VAS for quality of life
timeFrame: one year
Other outcomes:
measure: areal bone mineral density (aBMD)
timeFrame: one year
Locations:
city: Aarhus
country: Denmark
facility: Department of Rheumatology, Aarhus University Hospital
Study officials:
affiliation: Department of Rheumatology - Aarhus University Hospital
name: Ellen-Margrethe Hauge, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Klose-Jensen R, Therkildsen J, Blavnsfeldt AG, Langdahl BL, Zejden A, Thygesen J, Keller KK, Hauge EM. Diagnostic accuracy of high-resolution peripheral quantitative computed tomography and X-ray for classifying erosive rheumatoid arthritis. Rheumatology (Oxford). 2022 Mar 2;61(3):963-973. doi: 10.1093/rheumatology/keab446.