Progression of Bone Erosions in Rheumatoid Arthritis Assessed by HR-pQCT and Conventional X-ray (RACTX)

An Observational Study of Bone Erosion Determination and Progression in Rheumatoid Arthritis Assessed by HR-pQCT and Conventional X-ray

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Arthritis, Rheumatoid

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)

• Study Type: Observational
• Enrollment (Anticipated): 625

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8000
    • Department of Rheumatology, Aarhus University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• 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.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Rheumatoid arthritis; Patients with Rheumatoid arthritis ≥5 years according to the ACR/EULAR 2010 classification criteria or the American Rheumatism Association 1987 revised criteria. ICD-10: M059 Seropositive rheumatoid arthritis UNS, M060 Seronegative rheumatoid arthritis, M069 Rheumatoid arthritis UNS.
Pre-Rheumatoid arthritis; Patients with joint pain, but no swelling and Anti-CCP 3 times above the upper limit.
Healthy Subjects; Healthy age- and sex-matched Individuals are recruited, as a control group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Erosion changes by HR-pQCT	Changes in bone erosions volume in mm3 by HR-pQCT-imaging from baseline to one-year follow-up, in the three groups.	One year
Volumetric bone mineral density(vBMD) changes by HR-pQCT	Changes in volumetric bone mineral density(vBMD) in mgHA/cm3 by HR-pQCT-imaging from baseline to one-year follow-up, in the three groups.	One year
Erosion changes by HR-pQCT	Changes in bone erosions width in mm by HR-pQCT-imaging from baseline to one-year follow-up, in the three groups.	One year
Erosion changes by HR-pQCT	Changes in bone erosions depth in mm by HR-pQCT-imaging from baseline to one-year follow-up, in the three groups.	One year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic erosion score	Change in Sharp/van der Heijde (SvH) score from baseline to one-year follow-up, in the three groups.	One year
CTX	Changes from baseline to one-year follow-up in C-terminal telopeptide (CTX) in pg/mL, in the three groups.	one year
P1NP	Changes from baseline to one-year follow-up in Procollagen type 1 N-terminal propeptide (P1NP) in pg/mL, in the three groups.	one year
BAP	Changes from baseline to one-year follow-up in Bone-specific alkaline phosphatase (BAP) in pg/mL, in the three groups.	one year
TNF-α	Changes from baseline to one-year follow-up in the Tumor necrosis factor-alfa (TNF-α) in pg/mL, in the three groups.	one year
RANK-L	Changes from baseline to one-year follow-up in RANK-Ligand (RANK-L) in pg/mL, in the three groups.	one year
OPG	Changes from baseline to one-year follow-up in Osteoprotegerin (OPG) in pg/mL, in the three groups.	one year
BGLAP	Changes from baseline to one-year follow-up in Osteocalcin (BGLAP) in pg/mL, in the three groups.	one year
SCL	Changes from baseline to one-year follow-up in Sclerostin(SCL) in pg/mL, in the three groups.	one year
Dkk-1	Changes from baseline to one-year follow-up in Dickkopf-related protein 1 (Dkk-1) in pg/mL, in the three groups.	one year
IL-1	Changes from baseline to one-year follow-up in Interleukins 1 (IL-1) in pg/mL, in the three groups.	one year
IL-6	Changes from baseline to one-year follow-up in Interleukins 6 (IL-6) in pg/mL, in the three groups.	one year
IL-15	Changes from baseline to one-year follow-up in Interleukins 15 (IL-15) in pg/mL, in the three groups.	one year
IL-16	Changes from baseline to one-year follow-up in Interleukins 16 (IL-16) in pg/mL, in the three groups.	one year
IL-17	Changes from baseline to one-year follow-up in Interleukins 17 (IL-17) in pg/mL, in the three groups.	one year
IL-22	Changes from baseline to one-year follow-up in Interleukins 22 (IL-22) in pg/mL, in the three groups.	one year
IL-33	Changes from baseline to one-year follow-up in Interleukins 33 (IL-33) in pg/mL, in the three groups.	one year
CCL11	Changes from baseline to one-year follow-up in Chemokine ligand 11 (CCL11) in pg/mL, in the three groups.	one year
CXCL13	Changes from baseline to one-year follow-up in Chemokine (C-X-C) motif ligand (CXCL13) in pg/mL, in the three groups.	one year
TRACP 5b	Changes from baseline to one-year follow-up in Tartrate-resistant acid phosphatase 5b (TRACP 5b) in pg/mL, in the three groups.	one year
CRP	Changes from baseline to one-year follow-up in C-reactive protein (CRP) in mg/L, in the three groups.	one year
Disease Activity Score	Disease Activity Score (DAS28-CRP) [2.0-10.0]	one year
Health Assessment Questionnaire	Health Assessment Questionnaire (HAQ) [0-3 HAQ Total Score]	one year
VAS for pain	Visual Analog Scale(VAS) for pain [0-100mm]	one year
VAS for fatigue	Visual Analog Scale(VAS) for fatigue [0-100mm]	one year
VAS for quality of life	Visual Analog Scale(VAS) for quality of life [0-100mm]	one year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
areal bone mineral density (aBMD)	aBMD in the lumbar spine, and the left hip by DXA, in RA patients	one year

Collaborators and Investigators

• Sponsor: Aarhus University Hospital
• Collaborators: University of Aarhus
• Investigators: Study Director: Ellen-Margrethe Hauge, MD, PhD, Department of Rheumatology - Aarhus University Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2018
• Primary Completion (Anticipated): February 1, 2022
• Study Completion (Anticipated): December 31, 2026

Study Registration Dates

• First Submitted: January 24, 2018
• First Submitted That Met QC Criteria: February 5, 2018
• First Posted (Actual): February 12, 2018

Study Record Updates

• Last Update Posted (Actual): January 13, 2021
• Last Update Submitted That Met QC Criteria: January 12, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Rheumatoid Arthritis; High-resolution peripheral quantitative computed tomography; Radiography
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: RACTX

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No