Gaining Insight Into the Complexity of Pain in Patients With Haemophilia

NCT05606640 | Completed DMC

• 5 other identifiers: PAINSTUDY_20192019/28OCT/469B30020194230419/43/483EDGE000540
• Study Type: observational
• Target: 104
• Locations: 1 country
• Sites: 2

Brief Summary

Joint pain has been reported as a major problem in people with haemophilia (PwH). Therefore, haemophilia in adults seems clinically more related to a musculoskeletal disorder than a bleeding disorder, with many patients reporting a pain intensity exceeding 6/10 on a visual analogue scale. However, although the complexity of joint pain has been studied in chronic joint pain conditions such as low back pain, osteoarthritis or rheumatoid arthritis, until present only very limited research has been done on joint pain within PwH. Therefore, exploring the underlying mechanisms and the functional implications of this intense joint pain is urgently needed. As such, the main aim of the current prospective observational study is to gain more insights in joint pain in PwH enabling us to move towards adequate pain management in PwH.

Conditions

Hemophilia A; Hemophilia B

Keywords

Haemophilia; arthropathy; Pain; Biopsychosocial

Outcome Measures

Primary Outcomes (28)

• Pain localisation

  The body chart of the Brief Pain Inventory (BPI) was used to investigate painful body sites.

  At baseline (T0)

• Pain localisation

  The body chart of the Brief Pain Inventory (BPI) was used to investigate painful body sites.

  At one year follow-up (T2)

• Pain severity

  The BPI was used to evaluate the individual's pain experience within the last 24 hours by four items, resulting in a total pain severity score. Minimum score 0, maximum score 10. The higher te score, the higher the pain severity.

  At baseline (T0)

• Pain severity

  The BPI was used to evaluate the individual's pain experience within the last 24 hours by four items, resulting in a total pain severity score. Minimum score 0, maximum score 10. The higher te score, the higher the pain severity.

  At one year follow-up (T2)

• Pain interference

  The BPI was used to evaluate how much pain interferes with patient's daily activities. This was assessed by seven items, resulting in a total pain interference score. Minimum score 0, maximum score 10. The higher the score, the more pain interference.

  At baseline (T0)

• Pain interference

  The BPI was used to evaluate how much pain interferes with patient's daily activities. This was assessed by seven items, resulting in a total pain interference score. Minimum score 0, maximum score 10. The higher the score, the more pain interference.

  At one year follow-up (T2)

• Signs of neuropathic pain

  The Douleur Neuropathique en 4 questions (DN4) was applied as a screening tool for the presence of a neuropathic pain component. Minimum score 0, maximum score 10, a score of ≥4/10 was used as a cut-off.

  At baseline (T0)

• Signs of central sensitization

  The Central Sensitisation Inventory (CSI) part A was used to identify signs of central sensitization (CS) i.e. increased sensitivity of nociceptive neurons in the central nervous system.The presence of 25 pain-related psychological, cognitive and functional signs are scored from 0 (never) to 4 (always). A total score exceeding ≥40/100 indicated central sensitization.

  At baseline (T0)

• Pain Catastrophizing

  The Pain Catastrophizing Scale (PCS) asked participants to reflect on previous painful experiences and to rate their degree of catastrophic thinking in the content domains of rumination, magnification and helplessness. A score of 0 (not at all) to 4 (all the time) was indicated for each of the 13 items, resulting in a total score range of 0-52. Higher scores were associated with higher levels of pain catastrophizing.

  At baseline (T0)

• Anxiety and Depression

  The Hospital Anxiety and Depression Scale (HADS) was used to establish symptoms of anxiety and depression. This 14-item questionnaire consists of two subscales each including 7 items, the first to identify anxiety and the second depression. Individual items were scored from 0 to 3, resulting in a total range score of 0-21 for each subscale. A score of ≥8/21 was determined as a cut-off, indicating anxiety and depression.

  At baseline (T0)

• Fear Avoidance and Beliefs

  The fear avoidance and beliefs questionnaire (FABQ) will be used to assess fear avoidance behaviors. The first five items question physical activity, the other 11 activities work. A minimum score is 0, maximum 24. Higher scores indicate fear avoidance behaviors.

  At baseline (T0)

• Life quality

  The EQ-5D-5L was used to assess quality of life. From five items investigating the impact of their disease, a health utility score was calculated. Additionally, the questionnaire consists of a visual analogue scale (VAS) labelled from 0: "worst imaginable health state," to 100 "best imaginable health state" providing the EQ-VAS.

  At baseline (T0)

• Life quality

  The EQ-5D-5L was used to assess quality of life. From five items investigating the impact of their disease, a health utility score was calculated. Additionally, the questionnaire consists of a visual analogue scale (VAS) labelled from 0: "worst imaginable health state," to 100 "best imaginable health state" providing the EQ-VAS.

  At one year follow-up (T2)

• Haemophilia Activity Limitations

  The Haemophilia Activity List (HAL) was used to assess activity limitations and participation restrictions people with haemophilia suffer with. A sum score and component scores can be calculated, resulting in scores ranging from 0-100. Lower scores represent higher levels of participation restrictions.

  At baseline (T0)

• Physical endurance ability

  The 2 minutes walking test (2MWT) was used as a performance-based test to assess their functional activity. Subjects were asked to walk as far as possible for two minutes in a 30 meters flat corridor, resulting in the walking distance in meters.

  At baseline (T0)

• Physical functioning

  The Timed Up \& Go (TUG) consists of asking the patient to sit on a standard armchair; stand up and walk 3 meters; turn around at the line and walk back to the chair and sit down at a normal pace.

  At baseline (T0)

• Joint structure US

  Ultrasound (US) examinations will be performed with a linear probe (3-13 MHz) Esaote, type MyLab Gamma, Genova, Italy).The Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) scanning procedure and scoring method will be performed by one of our investigators. A score of 0/8 (normal bone 0/2, normal cartilage 0/4, absent hypertrophic synovium 0/2) is considered normal. A score above 1/8 is considered as abnormal.

  At baseline (T0)

• Joint structure MRI

  Magnetic Reasoning Imaging (MRI) of the ankles will be performed with a 3T-magnet (GE Signa Premier, GE Healthcare, Milwaukee, USA).Joint images will be classified with the international Prophylaxis Study Group (IPSG) scale. Joints will be classified as abnormal if talocrural joints or subtalar joints were positive at IPSG-score. Joints will be considered healthy if the total score was of 1/17.

  At baseline (T0)

• Illness perceptions

  The illness perceptions questionnaire (B-IPQ) includes nine items ranging from 0 (minimum) to 10 (maximum) and questions the perceptions related to the patients disease. No total score exists, as each item is scored individually. Higher scores indicate more negative or unhelpful illness perceptions. A change score between baseline (T0) and one year follow-up (T2) will be calculated.

  At baseline (T0)

• Illness perceptions

  The illness perceptions questionnaire (B-IPQ) includes nine items ranging from 0 (minimum) to 10 (maximum) and questions the perceptions related to the patients disease. No total score exists, as each item is scored individually. Higher scores indicate more negative or unhelpful illness perceptions. A change score between baseline (T0) and one year follow-up (T2) will be calculated.

  At one year follow-up (T2)

• Physical activity

  The International Physical Activity Scale (IPAQ) questions the hours of physical activity over the last week (Higher scores are higher levels of physical activity). Based on the patient's answers a MET-minute score is calculated (MET-minutes x weight in kilograms/60kilograms)

  At baseline (T0)

• Physical activity

  The International Physical Activity Scale (IPAQ) questions the hours of physical activity over the last week. Based on the patient's answers a MET-minute score is calculated (MET-minutes x weight in kilograms/60kilograms)

  At one month follow-up (T1)

• Joint function

  Joint function of the ankles, knees and ankles was assessed with the HJHS 2.1. Minimum score is 0, maximum, 20. The higher the score the more functional limitations. HJHS scores are considered positive when scores reach 1/20.

  At baseline (T0)

• Warm and cold detection threshold

  Thermal hyper or hypo esthesia were assessed with a thermode attached at the dominant wrist by use of a validated Quantitative Sensory testing protocol with the Medoc TSA-2 device.

  At baseline (T0)

• Warm and cold pain thresholds

  Thermal hyper or hypo algesia were assessed with a thermode attached at the dominant wrist by use of a validated Quantitative Sensory testing protocol with the Medoc TSA-2 device.

  At baseline (T0)

• Mechanical pain thresholds

  Mechanical local and widespread hyperalgesia indicated by lower pressure pain thresholds were assessed with a digital algometer at the knee joints, ankle joints and forehead. This by use of a validated quantitative sensory testing protocol.

  At baseline (T0)

• Temporal summation of pain

  Temporal summation (or bottom-up sensitization) of pain was assessed by use of a 60g Von Frey monofilament at the medial knee and dorsal side of the wrist of the dominant side.

  At baseline (T0)

• Conditioned Pain Modulation

  Dysfunctional endogenous pain inhibition (as form of central pain processing) was assessed by a validated protocol applying the Medoc TSA-2 device with thermodes attached at both wrists.

  At baseline (T0)

Secondary Outcomes (7)

• Pain interference change

  Change from baseline (T0) to one year follow-up (T2)

• Pain severity change

  Change from baseline (T0) to one year follow-up (T2)

• Fear Avoidance and beliefs change

  Change from baseline (T0) to one year follow-up (T2)

• Anxiety and Depression change

  Change from baseline (T0) to one year follow-up (T2)

• Illness Perceptions change

  Change from baseline (T0) to one year follow-up (T2)

Study Arms (1)

Haemophilia

Adult males with severe or moderate haemophilia A or B

Diagnostic Test: Biopsychological pain assessment

Interventions

Biopsychological pain assessment DIAGNOSTIC_TEST

At baseline (T0) patients underwent the somatosensory pain assessment, joint structure and function assessment and filled in all questionnaires. During one month after baseline (T1) patients wore an activity tracker and filled in the Illness Perceptions Questionnaire and the International Physical Activity questionnaire. During one year after the baseline assessment (T2) patients filled in every month The Brief Pain Inventory, Illness Perceptions Questionnaire and the EQ-5D-5L quality of life questionnaire.

Also known as: Pain-related questionnaires: Brief Pain Inventory, Douleur Neuropathique en 4 questions, Central Sensitization Inventory, Psychological questionnaires: Pain Catastrophizing Scale, Hospital Anxiety and Depression Scale, Fear Avoidance and Beliefs Questionnaire, The EuroQol-5 (EQ-5D-5L) quality of life questionnaire, Functional questionnaires: Haemophilia Activity List, International Physical Activity Questionnaire (IPAQ), Joint structure: Magnetic Reasoning Imaging (MRI) ankles & ultrasound evaluation of affected joints, Joint function: Hemophilia Joint Health Score (HJHS 2.1), Timed Up & Go, 2 minutes walking test, activity tracker, Somatosensory pain assessment: Quantitative Sensory testing protocol, Conditioned Pain Modulation protocol

Haemophilia

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Adult males with moderate or severe Haemophilia A or B will be recruited from the Haemophilia Treatment Centers in Antwerp (Antwerp University Hosptial) and Brussels (Cliniques universitaires Saint-Luc). Age-matched healthy control subjects will be recruited from family and acquintances of the researchers and hospital/university personnel.

You may qualify if:

• adult (18-65y) patients with moderate (i.e. between 1 and 5 % normal Factor activity) or severe (less than 1% normal Factor activity) Haemophilia A (i.e. Factor VIII deficiency) or B (i.e. Factor IX deficiency)
• Dutch or French speaking
• Patients who provide their haemophilia treatment regimen to be stable (i.e. a regular treatment during the last 6 months, verified by the existing patients' logbook).

You may not qualify if:

• Patients suffering from known neuropathies with definite medical causes independent from the haemophilia (e.g. diabetes polyneuropathy)
• Patients with a haemarthrosis in the month preceding study participation will be excluded as well. In case of doubt, ultrasound will be used to check the presence of bleed in the joint.

Sponsors & Collaborators

• Universiteit Antwerpen: lead
• Cliniques universitaires Saint-Luc- Université Catholique de Louvain: collaborator
• University Hospital, Antwerp: collaborator

Study Sites (2)

University Hospital Antwerp

Edegem, Antwerp, 2650, Belgium

Location

Cliniques universitaires Saint-Luc

Brussels, 120, Belgium

Location

MeSH Terms

Conditions

Hemophilia A; Hemophilia B; Joint Diseases; Pain

Interventions

Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Nathalie Roussel

  Universiteit Antwerpen

  PRINCIPAL INVESTIGATOR

• Cedric Hermans

  Cliniques universitaires Saint-Luc / UCLouvain

  PRINCIPAL INVESTIGATOR

• Catherine Lambert

  Cliniques universitaires Saint-Luc / UCLouvain

  PRINCIPAL INVESTIGATOR

• Sébastien Lobet

  Cliniques universitaires Saint-Luc / UCLouvain

  PRINCIPAL INVESTIGATOR

• Philip Maes

  University Hospital, Antwerp

  PRINCIPAL INVESTIGATOR

• Anthe Foubert

  University of Antwerp - UCLouvain

  PRINCIPAL INVESTIGATOR

• Valérie-Anne Chantrain

  University of Antwerp - UCLouvain

  PRINCIPAL INVESTIGATOR

• Mira Meeus

  Universiteit Antwerpen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Rehabilitation Sciences and Physiotherapy

Study Record Dates

• First Submitted: October 28, 2022
• First Posted: November 7, 2022
• Study Start: February 13, 2020
• Primary Completion: February 28, 2023
• Study Completion: October 13, 2023
• Last Updated: May 31, 2024

Record last verified: 2024-05

Locations

BE (2)