Pain in Inflammatory Joint Diseases (Nor-Pain)

Advancing the Understanding of Pain Mechanisms in Inflammatory Arthritis Towards Precision Pain Management

Our primary objective is to better understand the etiology and consequences of chronic paint by using an explorative approach to identify phenotypes and endotypes of patients with inflammatory joint diseases, with a special focus on central sensitization and cognitive functioning as a key element in chronic pain. We will also examine the risk factors and clinical impact of these factors on pain, disease activity and treatment effects in a longitudinal study of patients with inflammatory joint disesases.

Study Overview

• Status: Recruiting
• Conditions: Arthritis; Arthritis, Psoriatic; Arthritis, Reactive; Arthritis, Juvenile Idiopathic; Spondyloarthritis (SpA); Arthritis,Rheumatoid
• Intervention / Treatment: Drug: Biological or targeted synthetic DMARD

• Study Type: Observational
• Enrollment (Estimated): 350

Contacts and Locations

• Study Contact: Name: Ida K Haugen, MD PhD; Phone Number: +47 95859884; Email: ida.k.haugen@gmail.com

Study Locations

• Norway
  • Oslo, Norway
    • Recruiting
    • Diakonhjemmet Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of men and women (>18 years of age at screening) who are enrolled in the Nor-DMARD register and give their consent to also participate in this sub-study.

We will not have other inclusion and exclusion criteria than those that are already part of the Nor-DMARD register. This means that all patients who are being enrolled in the Nor-DMARD register will be asked to be part of this sub-study.

Description

Inclusion Criteria:

• All patients who initiate or switch biological or targeted synthetic DMARDs

Exclusion Criteria:

• None

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients who initiate or switch biological or targeted synthetic DMARD; All patients initiate or switch biological or targeted synthetic DMARD	Drug: Biological or targeted synthetic DMARD; All biological or targeted synthetic DMARDs that are available for treatment of patients with inflammatory joint diseases

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PROMIS Pain Interference - Short Form 8a	PROMIS Pain Interference - Short Form 8a assesses to which extend pain affect various aspects in daily life. This includes 8 items covering social, emotional, physical, and recreational activities [74], such as "How much did pain interfere with your day-to-day activities?" and "How much did pain interfere with your enjoyment of life?". The items have a 7-day time frame. Participants are asked to rate their responses on a three different 5-point Likert response scales. Scores are converted to a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD). Higher scores represent more pain interference.	Baseline, 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Social network	Questions about how many close friends the participants have, and whether they have a feeling of loneliness	Baseline
Gender role perception	One question is included regarding which gender the participants identify with, where the participant reports whether they identify with their biological gender, identify as non-binary or gender diverse, or wishes not to answer.	Baseline
Arthritis Self-Efficacy Scale (ASES)	We have included the pain subscale only. The pain subscale consists of five questions about how certain the respondent is that he/she can do the following tasks regarding their rheumatic pain. The response categories are 10-100 with 10 points increment between each response categories, with "moderately certain" is placed midway between "very uncertain" and "very certain". TA sum score is created based on the average of the five questions (10-100 scale) with higher score representing higher self-efficacy.	Baseline
Pain Catastrophizing Scale (PSC)	The PCS is a thirteen-item self-report scale to measure pain catastrophizing. The PCS consists of thirteen questions, and the respondents are instructed to reflect on past painful experiences and to indicate whether they have experienced each of the thirteen thoughts or feelings during their past experience of pain. Each question is rated from 0 ("not at all") to 4 ("all the time"). A total score and three subscale scores regarding helplessness (item 1-5 and 12), magnification (item 6-7 and 13) and rumination (item 8-11) can be calculated.	Baseline
Douleur Neuropathique 4 (DN4)	The DN4 questionnaire is a screening tool used to assess neuropathic pain. It consists of ten items. Seven items are related to pain symptoms based on an interview with the participant. The remaining three related to neurological symptoms based on a clinical examination. The examination includes assessment of whether there is reduced sensation (hypoesthesia) to touch or pinprick and whether light brushing increases or causes pain (allodynia) at a painful location. The scores are summarized and score 4 and above indicates neuropathic pain.	Baseline and 3 months
Painful joint count (Homunculus)	The participants mark their painful or aching joints (bilateral shoulders, elbows, wrists, hips, knees, ankles and feet as well as the neck, upper, middle, and lower back) the last 24h and the previous six weeks on a homunculus. The painful or aching hand and foot joints the last 24h or previous six weeks are marked on a hand and foot diagram. All painful hand joints are accumulated and counted as one "hand or foot joint" in a total body painful joint count (range: 0-20).	Baseline and 3 months
Patient Health Questionnaire (PHQ)	The PHQ-9 is the depression module, and contains nine items which scores each of the Diagnostic and Statistical Manual of Mental Disorders-IV criteria on a 4-point Likert scale (0-3). Major depression is diagnosed if 5 or more of the 9 depressive symptom criteria have been present at least "more than half the days" in the past 2 weeks, and 1 of the symptoms is depressed mood or anhedonia. Other depression is diagnosed if 2-4 depressive symptoms have been present at least "more than half the days" in the past 2 weeks, and 1 of the symptoms is depressed mood or anhedonia. The PHQ-9 sum score ranges from 0 to 27.	Baseline
General Anxiety Disorder Questionnaire (GAD-7)	The GAD-7 questionnaire is a seven-item, self-report anxiety questionnaire which assesses the patient's health status the previous 2 weeks [70]. The items enquire about the degree to which the patient has been bothered by feeling nervous, anxious or on edge, not being able to stop or control worrying, worrying too much about different things, having trouble relaxing, being so restless that it is hard to sit still, becoming easily annoyed or irritable and feeling afraid as if something might happen. The GAD-7 uses a 4-point Likert scale (0-3), and the sum score ranges from 0 to 21. Scores of 5, 10 and 15 represent cut-off points for mild, moderate and severe anxiety, respectively.	Baseline
MetaCognitions Questionnaire 30* (MCQ-30)	MCQ-30 consists of five factors that measure the following dimensions on a four-point scale (1-4): (1) positive beliefs about worry (e.g. "worrying helps me cope"); (2) negative beliefs about the uncontrollability and danger of worry (e.g. "when I start worrying I cannot stop"); (3) cognitive confidence (e.g. "my memory can mislead me at times"); (4) beliefs about the need to control thoughts (e.g. "not being able to control my thoughts is a sign of weakness"); and (5) cognitive self-consciousness (e.g. "I pay close attention to the way my mind works"). Likert scale ranging from 1 (do not agree) to 4 (agree very much) is used to rate the responses. Higher scores indicate higher levels of maladaptive metacognitive beliefs. A total score (range 30-120) and subscale scores of the five factors (range 6-24) can be calculated.	Baseline
Stanford Expectation of Treatment Scale (SETS)	SETS is a self-report questionnaire consisting of nine items rated on a 7-point scale, ranging from "strongly disagree" to "strongly agree" whilst assessing positive and negative treatment expectancies. The positive and negative expectations are scored separately in subscales.	Baseline
Gender Role Expectations of Pain (GREP)	The GREP questionnaire comprises twelve Visual Analogue Scales (VAS) items. The questions are answered according to the participants own gender and includes the following; whether the participants perceive themselves to be more sensitive to/endurable to/willing to report pain than the typical woman, whether the participants perceive themselves to be more sensitive to/endurable to/willing to report pain than the typical man, whether the participants perceive the typical man to be more sensitive to/endurable to/willing to report pain than the typical woman, and whether the participants perceive the typical woman to be more sensitive to/endurable to/ willing to report pain than the typical man. Each item is scored on a scale (100 mm line) ranging from "much less" on the left side of the scale and "much more" on the right, and a score of 50 suggests no difference between men and women.	Baseline
American College of Rheumatology (ACR) criteria for fibromyalgia	The questionnaire consists of 31 items based on the Widespread Pain Index (WPI), which divides the body into 19 regions and scores how many regions are reported as painful, and a symptom severity score which assesses severity of fatigue, unrefreshing sleep, and cognitive symptoms the previous week. Symptom severity of fibromyalgia related symptoms such as headaches, pain or cramps in lower abdomen and depression during the previous 6 months is also assessed.	Baseline
Cambridge Neuropsychological Test Automated Battery (CANTAB)	Cognitive functioning will be assessed with CANTAB. The tests are digital with simple standardized voice-over instructions. All sessions are thus objective. The executive component of flexibility will be measured using the Intra-Extra Dimensional Shift (IED) task. The executive component of inhibitory control will be measured with the Stop Signal Task (SST).	Baseline
Height and weight	The height of the participants is measured in centimetres (one decimal) with the participants in standing position. The weight is measured with the participants wearing light indoor clothing and without shoes (kilogram, one decimal).	Baseline
Hand preference	Participants are asked if left or right is their dominant hand.	Baseline
Quantitative sensory testing (QST)	Pressure pain thresholds (PPT): The point at which a sensation from pressure first gets painful.; Conditioned pain modulation (CPM): The concept of higher pain thresholds after a conditioning stimulus due to endogenous pain inhibition. An inflated blood pressure cuff around the arm will used as the conditioning stimulus before repeating the pressure pain threshold.; Temporal summation: An increase in pain intensity during the repetition of identical noxious stimuli (i.e., ascending nociceptive facilitation). These concepts are tested by simple equipment such as a hand-held algometer to assess pain thresholds and weighted probes to assess temporal summation.	Baseline, 3 months
Biobank	We will collect three extra tubes of blood (one for EDTA tube for whole blood, one EDTA tube for plasma and one for serum- each tube with 2 ml of blood), that will be used in this sub-study. The samples will be stored in a certified biobank in a freezer at -70° C. They will be used for research purposes only and may include analysis of potential new biomarkers of disease activity or outcomes including deoxyribonucleic and ribonucleic acid analyses (genomics and transcriptomics), proteins, enzymes, signalling molecules and metabolites in the blood. Only genetic markers and sequences that are prevalent in the population or that have been associated with disease, disease-related symptoms or risk factors will be tested. Since these diseases are complex diseases with an interplay of several genes (each with only small effects) and other risk factors, patients will not be informed about the results.	Baseline
Psoriatic Arthritis Impact of Disease (PsAID)	The PsAID-9 short form is a patient-derived composite response index for clinical research assessing the effect PsA has on a patient's quality of life. It is based on nine domains assessing pain, fatigue, skin problems, work/leisure activities, functional capacity, discomfort, sleep disturbance, coping and emotional well-being. The total score is the sum of weighted NRS scores, with higher scores representative of poorer status. The questionnaire will be completed by patients with PsA.	Baseline and 3 months
Pain Metacognition Questionnaire (PMQ)	The Pain Metacognitions Questionnaire (PMQ) is a tool to investigate pain-related metacognition, which is a feature of worry/rumination about pain. The two-dimensional questionnaire includes nine questions measuring positive metacognitions, and twelve questions measuring negative metacognitions. For the positive subscale the sum score ranges from 0 to 27, and for the negative subscale the sum score ranges from 0 to 36. Higher scores reflect more unhelpful metacognitions.	Baseline and 3 months
Everyday Memory Questionnaire - revised (EMQ)	EMQ is a questionnaire that maps the participants´ experience of their own everyday memory. The questionnaire consists of thirteen questions divided into three categories; category 1 assesses retrieval/memory (seven questions), category 2 maps attention and working memory (four questions) and category 3 consists of two questions with no clear interpretation. The answers are reported on a Likert scale from 0 to 4, where 0 is "once or less in the last month" and 4 is "once or more per day". EMQ scores higher than the norm value are suggested to indicate more difficulties with memory, and scores >1 SD above the norm value may indicate a significantly self-perceived reduced memory.	Baseline and 3 months
Ultrasound of joints and tendons	To assess synovitis, a trained examiner will perform ultrasound examination of the bilateral elbows, wrists (radioulnar, radiocarpal and midcarpal joints), 1st to 5th metacarpophalangeal joints, 2nd to 5th proximal interphalangeal joints, knees, talocrulal joints, and 1st to 5th metatarsophalangeal joints. The bilateral extensor carpi radialis and tibialis posterior tendons will also be assessed. Grey-scale synovitis and power doppler activity will be scored on 0-3 scales. We will use validated atlases in order to increase reliability. The examination will be done at baseline for all participants. In patients with SpA and history of axial involvement only, ultrasound examination at follow-up will not be performed unless there are signs of arthritis / tenosynovitis at baseline (grey scale grade ≥ 2 or power Doppler grade ≥1). Other participants will also undergo an ultrasound examination at follow-up.	Baseline and 3 months
MRI	We will not perform MRI as part of the study. However, if the participant has recently (last 6 months) performed an MRI, we will record the date, which joints, signs of inflammation (yes/no), and a description of main findings. This is especially relevant for patients with SpA, who may have solely axial affection.	Baseline
Treatments	At baseline, we will record current and previous use of DMARDs, the reasons for discontinuation (lack of efficacy, side effects, or anti-drug antibodies). Current dose of corticosteroids and any intraarticular corticosteroid injections previous 3 months will be recorded at both visits. If systemic corticosteroids have been initiated or the dose has been increased due to an on-going disease flare, the date of the treatment change will be recorded. Treatments are also recorded in Nor-DMARD, but we will perform own recording to secure complete data regarding reasons for discontinuation of previous treatments, which is of relevance if we want to define patients refractory to treatments. Furthermore, it is important to record any newly started drugs, since they may affect the degree of pain and inflammation at the study visit.	Baseline

Collaborators and Investigators

• Sponsor: Diakonhjemmet Hospital
• Collaborators: University of Oslo

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2025
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: December 2, 2024
• First Submitted That Met QC Criteria: December 2, 2024
• First Posted (Actual): December 5, 2024

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Post-Infectious Disorders; Bone Diseases; Musculoskeletal Diseases; Pathologic Processes; Chronic Disease; Disease Attributes; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Infections; Spinal Diseases; Spondylarthropathies; Skin Diseases, Papulosquamous; Skin Diseases; Spondylitis; Psoriasis; Arthritis, Infectious; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Arthritis; Arthritis, Juvenile; Spondylarthritis; Arthritis, Rheumatoid; Arthritis, Psoriatic; Arthritis, Reactive; Complex Mixtures; Biological Products
• Other Study ID Numbers: DS-00850; 708967 (Other Identifier: Regional ethical committee)

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
• product manufactured in and exported from the U.S.: No