Clinical trial NCT05546294: The Effects of Exercise on Serum BDNF and Irisin Levels in Patients With Rheumatoid Arthritis
Official title: The Effects of Aerobic Exercise on Sleep Quality, Fatigue, Quality of Life, Depression, Serum BDNF and Irisin Levels in Patients With Rheumatoid Arthritis: A Prospective Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Rheumatoid Arthritis
Sleep Quality
Aerobic Exercise
Keywords: Rheumatoid Arthritis
Sleep Quality
Serum BDNF
Serum Irisin
Quality of Life
Fatigue
Depression
Lead sponsor: Afyonkarahisar Health Sciences University
Sponsor class: OTHER
First posted: 2022-09-19
Enrollment: 151
Sex: ALL
Minimum age (years): 20
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of our study is to investigate the effects of aerobic exercise on sleep quality, fatigue, quality of life, depression and serum BDNF and irisin levels, which are important biomarkers of sleep in patients with rheumatoid arthritis.

Detailed description: Rheumatoid arthritis (RA) is a chronic, progressive, autoimmune disease characterized primarily by inflammation of synovial joints and tendon sheaths of synovial nature.

Sleep disturbance in RA patients has a negative impact on their quality of life in addition to their mental and physical health. Exercise has been identified as an important non-pharmacological factor in improving sleep quality and mood in patients with rheumatoid arthritis.

Irisin is a myokine and adipokine that has anti-inflammatory effects and can help regulate energy expenditure. It is secreted from skeletal muscles after exercise, as well as from other tissues such as the liver, nerves, heart, kidneys and skin. It has been observed that serum irisin levels are decreased in RA patients with poor sleep quality compared to RA patients with good sleep quality.

BDNF, one of the biochemical parameters evaluating sleep, is a signal protein encoded by the BDNF gene located on chromosome 11. It belongs to the neurotrophin family, which regulates the survival, development and function of neurons. Neuronal activity is a powerful stimulant that elicits BDNF production. Thus, activation of brain areas associated with motor control during exercise contributes to increased BDNF production in the brain and additionally in plasma. During acute exercise, irisin stimulates BDNF expression in the hippocampus of the brain. In addition to the circadian variation of plasma BDNF, the blood concentration of BDNF has been shown to increase acutely in response to aerobic exercise that does not include resistance exercise. Moreover, it has been reported that people with higher basal serum BDNF concentrations have lower REM sleep and therefore less sleep disturbances.

This investigation was designed as prospective randomized controlled study. Participants were randomized into 3 groups; RA patients receiving aerobic and home exercise, RA patients receiving only home exercise and healthy control group.

As evaluation parameters, DAS28 Score, SF (Short form) -36 Quality of Life Scale, Pittsburgh Sleep Quality Index (PSQI), Fatigue Severity Scale (FSS), Beck Depression Inventory (BDI), 6 Minute Walk Test and Borg Scale will be evaluated with. It was planned that the evaluations were made and recorded by a blinded physician to the all patients with rheumatoid arthritis at the beginning of the treatment and at the end of the treatment.In the healthy control group, the evaluation parameters will be examined only once at the beginning of the study.

At the beginning of the treatment and at the end of the treatment (4th week), serum BDNF and irisin levels will be tested using the ELISA kit, with blood samples taken from the RA patients in the early morning. It will be checked whether there is a difference between the basal serum BDNF and irisin levels of rheumatoid arthritis patients with the blood sample taken only once in the early morning from the healthy control group.

Eligibility criteria: Inclusion Criteria: Patients were included in the study

* Male and female gender between the ages of 20 and 60 who were diagnosed with rheumatoid arthritis according to the 2010 ACR/EULAR diagnostic criteria,
* Patients with Disease Activity Score (DAS28) ≤3.2 (low disease activity or remission) (no change in anti-rheumatic drugs or steroid dose in the last 3 months),
* Patients who were being followed at Afyonkarahisar Health Sciences University Department of Physical Medicine and Rehabilitation,

Exclusion Criteria:

* Active malignancy and/or a history of malignancy within the past 5 years,
* Uncontrolled cardiopulmonary disease (such as severe hypertension, chronic obstructive pulmonary disease, stage 3 or 4 heart failure, significant left ventricular outflow obstruction, dissecting aneurysm, embolism or thrombophlebitis history),
* Patients who cannot tolerate cardiorespiratory exercise training due to unstable angina pectoris, dangerous cardiac arrhythmias and myocardial infarction in the last 3 months,
* Pregnancy or planning a pregnancy in the near future,
* History of major surgery (including joint surgery) within the last six months,
* Regular physical activity at least 3 days a week in the last 3 months,
* Orthopedic, neurological or mental disease that may affect exercise,

Primary outcomes:
measure: Change from baseline disease activity score (DAS28) at 4th week
timeFrame: Up to 4th week
Secondary outcomes:
measure: Change from baseline quality of life (short form 36 (SF-36)) at 4th week
timeFrame: Up to 4th week
measure: Change from baseline Fatigue Severity Scale (FSS) at 4th week
timeFrame: Up to 4th week
measure: Change from baseline Beck's Depression Inventory (BDI) at 4th week
timeFrame: Up to 4th week
measure: Change from baseline Pittsburgh Sleep Quality Index (PSQI) at 4th week
timeFrame: Up to 4th week
measure: Change from baseline Six Minute Walk Test (6MWT) at 4th week
timeFrame: Up to 4th week
measure: Change from baseline Borg Rating Of Perceived Exertion Scale (Borg RPE Scale) at 4th week
timeFrame: Up to 4th week
Other outcomes:
Locations:
city: Afyonkarahi̇sar
country: Turkey
facility: Afyonkarahisar Health Sciences University
Study officials:
affiliation: Afyonkarahisar Health Sciences University
name: Ümit DÜNDAR, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Afyonkarahisar Health Sciences University
name: Hatice Kudret MİROĞLU, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Baillet A, Zeboulon N, Gossec L, Combescure C, Bodin LA, Juvin R, Dougados M, Gaudin P. Efficacy of cardiorespiratory aerobic exercise in rheumatoid arthritis: meta-analysis of randomized controlled trials. Arthritis Care Res (Hoboken). 2010 Jul;62(7):984-92. doi: 10.1002/acr.20146.
citation: Gamal RM, Mohamed ME, Hammam N, El Fetoh NA, Rashed AM, Furst DE. Preliminary study of the association of serum irisin levels with poor sleep quality in rheumatoid arthritis patients. Sleep Med. 2020 Mar;67:71-76. doi: 10.1016/j.sleep.2019.10.021. Epub 2019 Nov 30.
citation: Tan X, van Egmond LT, Cedernaes J, Benedict C. The role of exercise-induced peripheral factors in sleep regulation. Mol Metab. 2020 Dec;42:101096. doi: 10.1016/j.molmet.2020.101096. Epub 2020 Oct 9.