Effect of Antiinflammatory Treatment Versus Hand Training on Neuropsychiatric Comorbidity in RA-patients

NCT04378621 | Unknown

• 1 other identifier: NeuMRA
• Study Type: interventional
• Target: 212
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate how RA affect the brain structures in RA-patients and if anti-inflammatory treatment that target TNF-α or JAK OR physical training of hands has positive impact on neuropsychiatric symptoms and morphological changes in the brain caused by the disease. The goal of this research project is to improve the knowledge of morphological changes in brain developed in connection to RA and to identify clinical and serological markers to predict development of those changes and finally, to investigate if anti-rheumatic interventions counteract destructive processes in the central nervous system (CNS) and improve the patient's health with respect to functionality, pain experience and psychological well-being.

Conditions

Rheumatoid Arthritis; Pain; Fatigue; Cognitive Decline; Depression; Brain Diseases; Hand Rheumatism

Keywords

Rheumatoid arthritis; RA; neuropsychiatric comorbidity

Outcome Measures

Primary Outcomes (16)

• Difference in regional brain volume

  Magnetic resonance imaging (MRI) of all patients brains will be performed at base-line and at follow-up visit after 6 months. Measurement of 83 anatomical regions of the brain will be performed to detect subtle changes in volume. This is performed using multiatlas propagation with enhanced registration (MAPER) and the 2017 version of the Hammersmith atlas database. The difference in regional brain volume between study visits will be calculated.

  Difference in brain regional volume from base-line to follow-up study visit after 6 months

• Difference in Disease activity score (DAS28)

  Scoring of disease activity for all patients will be performed at base-line and at follow-up visit after 6 months. Disease Activity Score is a standardised indicator of RA disease activity calculated as a composite score of: number of tender and swollen joints (assessed by trained personnel), erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) and the patients assessment of pain on a visual analogue scale of 10 mm (VAS). The difference in Disease activity score between study visits will be calculated.

  Difference in DAS28 score from base-line to follow-up study visit after 6 months

• Difference in Tender Point score (TP18)

  Scoring of tender Points for all patients will be performed at base-line and at follow-up visit after 6 months. Tender points are sensitive areas on the body that elicit pain and tenderness when pressure is applied. The TP 18 protocol is a standardised measurement of number of painful/tender points out of 18 bilateral points on the body. The difference in Tender Point score between study visits will be calculated.

  Difference in TP18 score from base-line to follow-up study visit after 6 months

• Difference in Pain VAS score

  Scoring of Pain VAS will be performed daily by all patients and recorded in a pain diary. Pain VAS is the patients scoring in mm of overall perceived pain on a 10 mm long visual analogue scale. The difference in Pain VAS score between daily recordings will be calculated.

  Difference in Pain VAS score from base-line to follow-up study visit after 3 and 6 months

• Difference in hand joint mobility

  Measurement of hand joint mobility for all patients will be performed at base-line and at follow-up visit after 3 and 6 months. Hand joint mobility is clinically assessed by occupational therapist according to a standardised protocol and reported as degrees of mobility in extension/flexion and pronation/supination of the hand joint. The difference in degrees of hand joint mobility between study visits will be calculated.

  Difference in hand joint mobility from base-line to follow-up study visits after 3 and 6 months

• Difference in finger joint mobility

  Measurement of finger joint mobility for all patients will be performed at base-line and at follow-up visit after 3 and 6 months. Finger joint mobility is clinically assessed by occupational therapist according to standardised protocol and reported as degrees of mobility in extension/flexion of each finger. The difference in degrees of finger joint mobility between study visits will be calculated.

  Difference in finger joint mobility from base-line to follow-up study visits after 3 and 6 months

• Difference in hand grip strength

  Measurement of hand grip strength for all patients will be performed at base-line and at follow-up visit after 3 and 6 months. Hand grip strength is clinically assessed by occupational therapist and performed using Grippit®, a standardised electronic handheld instrument used for measuring hand strength in the cylinder grip. The patient is instructed to grip the Grippit® and squeeze it as hard as possible for 10 seconds. The instrument generates three values; the maximal value of force applied, the mean value of force applied during the 10 seconds and a final value measured during the last half a second. The values are reported in Newton (N). Both hands are examined and which of the hands that is dominant is noted. The difference in Newton between study visits will be calculated.

  Difference in hand grip strength from base-line to follow-up study visits after 3 and 6 months

• Difference in hand/finger joint deformities

  Documentation of hand/finger joint deformities for all patients will be performed at base-line and at follow-up visit after 3 and 6 months. Hand and finger joint deformities is clinically assessed by occupational therapist according to standardised protocol. Reported in text for each joint

  Difference in hand/finger joint deformities from base-line to follow-up study visits after 3 and 6 months

• Difference in RA-related skeletal changes

  Documentation of RA-related skeletal changes for all patients will be performed at base-line and at follow-up visit after 6 months. Radiological imaging of the hand joint will be performed using plain X-ray. The assessment of hand radiographs and scoring of possible joint damage will be performed by experienced rheumatologist. The difference in score between study visits will be calculated.

  Difference in RA-related skeletal changes from base-line to follow-up study visits after 6 months

• Difference in inflammatory markers

  Serum samples will be gathered from all patients at base-line and follow-up visit after 3 and 6 months. Levels of various inflammatory markers will be measured and the difference in levels between study visits will be calculated.

  Difference in inflammatory markers from base-line to follow-up study visits after 3 and 6 months

• Difference in DASH score

  DASH, "Disabilities of the Arm, Shoulder and Hand", is a self-administered questionnaire regarding symptoms and ability to perform certain activities. The questionnaire will be filled out by all patients at base-line and at follow-up visit after 3 and 6 months and scored according to established protocol. The difference in DASH score between study visits will be calculated.

  Difference in DASH score from base-line to follow-up study visits after 3 and 6 months

• Difference in FIQ score

  FIQ, "Fibromyalgia Impact Questionnaire", is a self-administered questionnaire regarding pain, fatigue, functional ability, quality of life etc. The questionnaire will be filled out by all patients at base-line and at follow-up visit after 3 and 6 months and scored according to established protocol. The difference in FIQ score between study visits will be calculated.

  Difference in FIQ score from base-line to follow-up study visits after 3 and 6 months

• Difference in HADS score

  HADS, "Hospital Anxiety and Depression Scale", is a self-administered questionnaire regarding anxiety and depression. The questionnaire will be filled out by all patients at base-line and at follow-up visit after 3 and 6 months and scored according to established protocol. The difference in HADS score between study visits will be calculated.

  Difference in HADS score from base-line to follow-up study visits after 3 and 6 months

• Difference in IPAQ score

  IPAQ, "International Physical Activity Questionnaire", is a self-administered questionnaire regarding physical activity and inactivity. The questionnaire will be filled out by all patients at base-line and at follow-up visit after 3 and 6 months and scored according to established protocol. The difference in IPAQ score between study visits will be calculated.

  Difference in IPAQ score from base-line to follow-up study visits after 3 and 6 months

• Difference in HAQ score

  HAQ, "Health Assessment Questionnaire", is a self-administered questionnaire regarding functional ability and overall health. The questionnaire will be filled out by all patients at base-line and at follow-up visit after 3 and 6 months and scored according to established protocol. The difference in HAQ score between study visits will be calculated.

  Difference in HAQ score from base-line to follow-up study visits after 3 and 6 months

• Difference in SF-36 score

  SF-36, "Short Form Health Survey", is a self-administered questionnaire regarding overall health. The questionnaire will be filled out by all patients at base-line and at follow-up visit after 3 and 6 months and scored according to established protocol. The difference in SF-36 score between study visits will be calculated.

  Difference in SF-36 score from base-line to follow-up study visits after 3 and 6 months

Secondary Outcomes (1)

• Difference in intestinal microbiome composition

  Difference in intestinal microbiome composition from base-line to follow-up study visits after 6 months

Study Arms (2)

Pharmacological anti-inflammatory treatment

EXPERIMENTAL

Use of anti-rheumatic treatment with TNF-α inhibitor (subcutaneous injection given once or twice a week) or JAK inhibitor (per oral tablet once or twice a day)

Drug: TNF-α inhibitor OR JAK inhibitor

Physical hand training

EXPERIMENTAL

Physical hand training 10 min twice daily while on stable treatment

Other: Hand training

Interventions

TNF-α inhibitor OR JAK inhibitor DRUG

Pharmacological anti-rheumatic treatment

Also known as: TNF-a inhibitors: Etanercept (Enbrel, Benapali), Infliximab (Remicade, Inflectra, Flixabi), Adalimumab (Humira, Imraldi, AMGEVITA), Certolizumabpegol (Cimzia), Golimumab (Simponi), JAK-inhibitors: Baricitinib (Olumiant), Tofacitinib (Xeljanz)

Pharmacological anti-inflammatory treatment

Hand training OTHER

Physical hand training 10 min twice daily while on stable treatment

Also known as: physiotherapy of hands

Physical hand training

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• confirmed RA diagnosis, in the early stage of the disease (1-3 years after the diagnosis, n=20); in the established stage of the disease (5-8 years after the diagnosis, n=30) and in the late stage of the disease (\>12 years after the diagnosis, n=30)

You may not qualify if:

• any conditions precluding MRI imaging; e.g claustrophobia; pacemaker etc, medical history of ischemic stroke or cerebral hemorrhage; medical history of neurological disease; inability to read and communicate in Swedish, hence being able to give informed consent and fill out study questionnaires

Sponsors & Collaborators

• Vastra Gotaland Region: lead

Study Sites (1)

Clinical Rheumatology Research Center (CRRC), Department of Rheumatology, Sahlgrenska University Hospital

Gothenburg, Sweden

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid; Pain; Fatigue; Cognitive Dysfunction; Depression; Brain Diseases

Interventions

Janus Kinase Inhibitors; Etanercept; Infliximab; Adalimumab; Certolizumab Pegol; golimumab; baricitinib; tofacitinib

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Behavioral Symptoms; Behavior; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antibodies, Monoclonal; Antibodies; Antibodies, Monoclonal, Humanized; Polyethylene Glycols; Polymers; Macromolecular Substances; Immunoglobulin Fab Fragments

Study Officials

• Maria Bokarewa, MD

  Dep of Rheumatology and Inflammation research, University of Gothenburg, Sweden

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Group A. Pharmacological treatment with TNF-α inhibitor or JAK inhibitor Group B. Physical hand training 10 min twice daily while on stable treatment with TNF-α inhibitor or JAK inhibitor

Study Record Dates

• First Submitted: April 8, 2020
• First Posted: May 7, 2020
• Study Start: October 1, 2020
• Primary Completion: September 1, 2025
• Study Completion: September 1, 2025
• Last Updated: May 4, 2022

Record last verified: 2022-05

Locations

SE (1)