Fatigue in Sjögren's Syndrome: 3 Therapeutic Strategies

Official title

Fatigue in Sjögren's Syndrome: a Randomized Controlled Trial of Combined Non-pharmacological Therapeutic Strategies

Overview

Unexplained fatigue is a frequent (60-70%) chronic complaint in Sjögren's syndrome (SjS) with a clear unmet therapeutic need, despite the recommendation of adapted physical activity (APA) programs, which are effective and feasible, but only to some extent. Hence, other therapeutic approaches, such as Acupuncture (ACU) or transcutaneous vagal nerve stimulation (tVNS), have been evaluated during the past years, with varying degrees of success in alleviating fatigue. FESSONA has been designed as a randomized controlled monocentric trial, aiming at comparing the effects of 3 different programs on fatigue in SjS: APA alone, APA+ACU and APA+tVNS. Relevant controls will be included as well (sham ACU and simulated tVNS). Multiple fatigue and SjS-related features will be measured before (at inclusion) and after (week 12) the intervention, as well as at week 24 and 48, to evaluate the short- and long-term impact of each program. Tolerance and feasibility will also be evaluated.

Interventions

• Device Acupuncture (ACU)
  acupoints will be Baihui (GV20); Zhongwan (CV12), Guanyuan (CV4), bilateral Zusanli (ST36) bilateral Taichong (LV3). The needles will remain for 30 min. Subjects will receive acupuncture twice a week during the 12-week intervention.
• Device Transcutaneous Vagus Nerve Stimulation (tVNS)
  Transcutaneous Vagus Nerve Stimulation (tVNS) will be performed using an ECO TENS 2 device with an ear clip put in the conque aurea of the left ear, which is innervated by the auricular branch of the vagus nerve. In the groups receiving simulated tVNS, stimulation will be delivered to the ear lobe, which is devoid of vagal innervation. Stimulation will be delivered at a frequency of 20 Hz and a pulse width of 200 ms, while the stimulation amplitude will be individually titrated to 1 mA below th
• Other APA (adapted physical activity )
  The APA (adapted physical activity ) program : 2 sessions of 90 min (with 60 min of aerobic exercise and 30 min of resistance exercises per session) per week, for 12 consecutive weeks
• Device Acupuncture (sham_ACU)
  Needles well be used in the non-acupoint area 2 centimeters away from the real acupoints. The needles will remain for 30 min. Subjects will receive sham acupuncture twice a week during the 12-week intervention.
• Device Simulated Transcutaneous Vagus Nerve Stimulation (sim_tVNS)
  Simulated Transcutaneous Vagus Nerve Stimulation (sim\_tVNS) will be performed using an ECO TENS 2 device with an ear clip put in the conque aurea of the left ear, which is innervated by the auricular branch of the vagus nerve. NSVt devices will be used in "simulated" mode.

Primary outcome measures

• Change in fatigue score assessed [Time frame: Between inclusion (week 0) and visit V1 at 12 weeks (± 1 week from the end of the 12-week program)]

Secondary outcome measures (12)

• FACIT-F score in the different groups [Time frame: between inclusion (Week 0) and week 48]
• Root Mean Square of the Successive Differences in heart rate or RMSSD (in milliseconds) [Time frame: at 12, 24 and 48 weeks,]
• Proportion (in %) of the 24 APA sessions carried out (at least 80% of the exercises proposed) in the different groups [Time frame: week 48]
• ClinESSDAI score [Time frame: at 12, 24 and 48 weeks,]
• ESSPRI questionnaire (EULAR Sjögren's Syndrome Patient Reported Index) [Time frame: at 12, 24 and 48 weeks]
• HADS questionnaire (Hospital Anxiety and Depression Scale) [Time frame: at 12, 24 and 48 weeks]
• Self-measurement questionnaire SF-36 (Short Form Health Survey 36) [Time frame: between inclusion (Week 0) and week 48]
• EQ-5D-5L self-measurement questionnaire assessing 5 dimensions of health [Time frame: at 12, 24, and 48 weeks,]
• Schirmer test [Time frame: at 12, 24 and 48 weeks]
• VO2max [Time frame: at 12, 24 and 48 weeks]
• Handgrip test [Time frame: at 12, 24 and 48 weeks]
• Number of daily steps [Time frame: at 12, 24 and 48 weeks]

Eligibility criteria

Inclusion criteria

• Patient affiliated or entitled to a social security scheme.
• Age > 18 years.
• Patient informed and having signed the information form and consent to participate in the study.
• Patient with Sjögren's syndrome according to ACR/EULAR 2016 or AECG 2002 criteria, usually followed up every year or more frequently
• Fatigue present for ≥ 6 months, without obvious explanation and/or specific treatment to conduct (e.g., disease's flare, chronic infection), with a current FACIT-F score < 34

Exclusion criteria

• Pre-existing atrial fibrillation or severe cardiac conduction disorders,
• Recent stroke or myocardial infarction (<6 months),
• Left ventricular ejection fraction <40% or severe heart failure (New York Heart Association functional class III or IV)
• Recurrent episodes of vasovagal syncope, or history of vagotomy
• People with dermatological problems in the area where the stimulation electrodes are to be placed
• Current episode of venous or arterial thrombosis
• Pregnancy or breastfeeding
• Patient under protective measures (legal protection, curatorship, guardianship)
• Inability or refusal to understand and/or sign informed consent to participate in the study, or to perform follow-up examinations required under the study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Other

Study locations

France · 1 center

• Chu de Saint-Etienne — Saint-Etienne

Publications

• Zhou X, Chen J, Colas C, Hupin D, Killian M. FatiguE in Sjogren's Syndrome: a randomised controlled trial of cOmbined Non-phArmacological therapeutic strategies (FESSONA). BMJ Open Sport Exerc Med. 2025 Jun 16;11(2):e002677. doi: 10.1136/bmjsem-2025-002677. eCollection 2025. PMID 40546749

Identifiers

NCT: NCT06875102 · 24CH125 · ANSM

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗