Fatigue in Sjögren's Syndrome: 3 Therapeutic Strategies

NCT ID: NCT06875102

Last Updated: 2025-07-08

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 174 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-31
• Study Completion Date: 2028-04-30

Brief Summary

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.

Conditions

Sjogren Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

APA + sham ACU + tVNS

Group Type: EXPERIMENTAL

Transcutaneous Vagus Nerve Stimulation (tVNS)

Intervention Type: DEVICE

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 the level that will lead to a mild unpleasant feeling, according to the parameters defined by Stavrakis et al (2017, 2020).

APA (adapted physical activity )

Intervention Type: OTHER

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

Acupuncture (sham_ACU)

Intervention Type: DEVICE

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.

APA + ACU + simulated tVNS

Group Type: EXPERIMENTAL

Acupuncture (ACU)

Intervention Type: DEVICE

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.

APA (adapted physical activity )

Intervention Type: OTHER

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

Simulated Transcutaneous Vagus Nerve Stimulation (sim_tVNS)

Intervention Type: DEVICE

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.

APA + Simulated tVNS + sham ACU

Group Type: SHAM_COMPARATOR

APA (adapted physical activity )

Intervention Type: OTHER

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

Acupuncture (sham_ACU)

Intervention Type: DEVICE

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.

Simulated Transcutaneous Vagus Nerve Stimulation (sim_tVNS)

Intervention Type: DEVICE

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.

Interventions

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.

Intervention Type: 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 the level that will lead to a mild unpleasant feeling, according to the parameters defined by Stavrakis et al (2017, 2020).

Intervention Type: DEVICE

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

Intervention Type: OTHER

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.

Intervention Type: 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.

Intervention Type: DEVICE

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Universitaire de Saint Etienne

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Martin KILLIAN, MD

Role: PRINCIPAL_INVESTIGATOR

Locations

Chu de Saint-Etienne

Saint-Etienne, , France

Countries

France

Central Contacts

Martin KILLIAN, MD

Role: CONTACT

martin.killian@chu-st-etienne.fr

(33)477 82 91 79 ext. +33

Florence RANCON, Chef de projet

Role: CONTACT

florence.rancon@chu-st-etienne.fr

(33)477829458 ext. +33

Facility Contacts

Martin KILLIAN, MD

Role: primary

martin.killian@chu-st-etienne.fr

(33) 4 77 82 91 79 ext. +33

Florence RANCON, Chef de projet

Role: backup

florence.rancon@chu-st-etienne.fr

(33) 4 77 82 94 58 ext. +33

References

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.

Reference Type: DERIVED

PMID: 40546749 (View on PubMed)

Other Identifiers

ANSM

Identifier Type: OTHER

Identifier Source: secondary_id

24CH125

Identifier Type: -

Identifier Source: org_study_id