StrokeESTIM-ULNCT07513714
ESTIM-UL: FES for Upper Limb Recovery After Stroke
A study testing Functional Electrical Stimulation (FES) and Conventional Rehabilitation in people with Stroke and Post-Stroke Spasticity, run by University of Foggia at 1 site in Italy.
Trial summary
Stroke is a leading cause of long-term disability, frequently resulting in impaired upper limb motor function and spasticity. Although Botulinum Toxin Type A (BoNT-A) is effective in reducing focal spasticity, functional recovery of the upper limb often remains limited without intensive, task-specific rehabilitation. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Stroke, Post-Stroke Spasticity, Post-Stroke Hemiparesis
- What is being tested?
- Functional Electrical Stimulation (FES) and Conventional Rehabilitation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteItaly
- Study dates
- 1 May 2026to 1 Dec 2026
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 years or older.
- Diagnosis of ischemic or hemorrhagic stroke, documented by CT or MRI.
- Clinical presence of focal upper limb spasticity, defined as a score ≥ 1+ on the Modified Ashworth Scale (MAS) in at least one target muscle group (elbow, wrist, or finger flexors), treated with Botulinum Toxin Type A injection.
- Presence of residual voluntary muscle activation (minimal active movement) sufficient to initiate the motor task required by the training (Box and Block score ≥ 1).
- Preserved cognitive function, defined as a Mini-Mental State Examination (MMSE) score ≥ 24 or clinical judgment confirming adequate comprehension and cooperation.
Who cannot join
- Absolute contraindications to Functional Electrical Stimulation (FES), including the presence of a cardiac pacemaker or implantable cardioverter defibrillator (ICD), pharmacologically uncontrolled epilepsy, or skin lesions/dermatitis at the electrode application sites.
- Presence of severe muscle-tendon contractures or fixed joint deformities (ankylosis) that mechanically limit passive movement and make active functional recovery unlikely.
- Severe cognitive impairment, global aphasia, or severe unilateral spatial neglect that prevents task comprehension or active participation in the training program.
- Concomitant orthopedic or rheumatologic conditions affecting the upper limb (e.g., recent fractures, severe arthritis) that could interfere with treatment delivery or outcome assessment.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Università degli studi di Foggia
Foggia, Foggia, 71121
Stefania Spina, phd, +39 0881736258, stefania_spina.559372@unifg.it
About this study
Official title: Efficacy of Functional Electrical Stimulation (FES) Combined With Task- Oriented Training on Upper Limb Recovery in Post-Stroke Patients With Spastic Hemiparesis: A Randomized Controlled Trial
Stroke is a leading cause of long-term disability, frequently resulting in impaired upper limb motor function and spasticity. Although Botulinum Toxin Type A (BoNT-A) is effective in reducing focal spasticity, functional recovery of the upper limb often remains limited without intensive, task-specific rehabilitation. Functional Electrical Stimulation (FES), when synchronized with voluntary movement during Task-Oriented Training, may enhance motor recovery by facilitating muscle activation and neuroplasticity. This randomized controlled trial aims to evaluate whether FES combined with Task-Oriented Training is superior to conventional Task-Oriented Training alone in improving upper limb function in post-stroke patients treated with BoNT-A.
Read the detailed description
Stroke remains one of the leading causes of long-term disability worldwide. Among its most disabling and persistent sequelae is impairment of upper limb motor function, affecting approximately 50-80% of stroke survivors in the acute phase and persisting in a substantial proportion of patients over time. Incomplete recovery of manual dexterity and fine motor control significantly limits independence in activities of daily living and negatively impacts quality of life. A major factor limiting upper limb recovery after stroke is the development of spasticity, a sensorimotor disorder resulting from upper motor neuron lesions. Upper limb spasticity typically evolves toward pathological flexor synergies which, if left untreated, lead to increased muscle tone, altered muscle-tendon properties, soft tissue shortening, and fixed joint deformities. These changes interfere with voluntary motor control, functional use of the limb, hygiene, and caregiving.
Current international guidelines identify focal injection of Botulinum Toxin Type A (BoNT-A) as the first-line treatment for focal upper limb spasticity. By blocking presynaptic acetylcholine release at the neuromuscular junction, BoNT-A induces a temporary chemical denervation that effectively reduces muscle overactivity. However, clinical experience and scientific evidence consistently demonstrate a frequent dissociation between technical success, defined as reduction in spasticity scores, and functional success, defined as improved active use of the upper limb. Reduction of muscle tone alone, although necessary, is not sufficient to restore voluntary motor control in a damaged central nervous system unless it is integrated into an intensive neuromotor rehabilitation program.
This observation has led to the concept of a "therapeutic window," in which BoNT-A reduces peripheral biomechanical resistance, creating favorable conditions that must be exploited through targeted adjunctive rehabilitation therapies. Among these, Task-Oriented Training (TOT), based on repetitive and intensive practice of meaningful functional tasks, represents one of the most effective approaches to promote post-stroke neuroplasticity.
Nevertheless, in patients with moderate to severe paresis, insufficient voluntary muscle activation often limits the effective execution of task-oriented exercises.
In this context, Functional Electrical Stimulation (FES) emerges as a key rehabilitative technology. Beyond inducing muscle contraction through peripheral nerve stimulation, FES acts as a powerful modulator of cortical plasticity. When synchronized with the patient's voluntary movement attempts, FES provides enhanced somatosensory feedback to the sensorimotor cortex. The coupling of motor intention, assisted execution, and afferent feedback reinforces synaptic connections according to Hebbian learning principles. Despite a strong neurophysiological rationale, there remains a lack of rigorous randomized controlled trials quantifying the specific added value of FES when combined with task- oriented rehabilitation in patients treated with BoNT-A. The present study is based on the hypothesis that applying FES to wrist and finger extensor muscles during Task-Oriented Training, in post-stroke patients previously treated with BoNT-A to inhibit spastic flexor muscles, produces a synergistic effect superior to conventional task-oriented rehabilitation alone. By simultaneously reducing spasticity-related resistance and enhancing muscle recruitment and cortical plasticity, this multimodal approach is expected to result in greater improvements in manual dexterity and overall upper limb function.
- Conditions
- Stroke, Post-Stroke Spasticity, Post-Stroke Hemiparesis
- Being tested
- Functional Electrical Stimulation (FES), Conventional Rehabilitation
- Keywords
- functional electrical stimulation, Botulinum Toxin Type A, stroke, motor recovery, upper limb
- Medical subject headings
- Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Functional Electrical Stimulation (FES)Device
Functional Electrical Stimulation is applied to wrist and finger extensor muscles of the paretic upper limb using a surface electrode system. Electrical stimulation is synchronized with the participant's voluntary movement attempts during Task-Oriented Training to facilitate active motor execution and sensorimotor integration. Stimulation is delivered during 60-minute rehabilitation sessions, 5 days per week for 2 consecutive weeks.
Conventional RehabilitationOther
Conventional rehabilitation consists of therapist-assisted Task- Oriented Training of the paretic upper limb, including manual facilitation and guidance as needed to support task execution. No electrical stimulation is applied. Sessions last 60 minutes and are performed 5 days per week for 2 consecutive weeks.
| Study group | Role | What they receive |
|---|---|---|
| Functional Electrical Stimulation plus Task-Oriented Training | Experimental | Participants in the experimental arm receive Task-Oriented Training of the affected upper limb with Functional Electrical Stimulation (FES) applied to upper limb muscles based on the movement. FES is delivered using a wireless stimulation system and is synchronized with the participant's voluntary movement attempts to facilitate active motor execution. The first module includes active Task-Oriented Training of the paretic upper limb, such as reaching, grasping, and object manipulation. During task execution, Functional Electrical Stimulation is applied to upepr limb muscles and is synchronized with the participant's voluntary movement attempts to facilitate active motor execution and provide proprioceptive feedback.The second module consists of conventional physiotherapy focused on joint mobilization (passive and active-assisted movements) and muscle stretching. Each session lasts 60 minutes and is conducted 5 days per week for 2 consecutive weeks (10 sessions total). Receives: Device: Functional Electrical Stimulation (FES) |
| Task-Oriented Training with Conventional Rehabilitation | Active comparator | Participants in the control arm receive Task-Oriented Training of the affected upper limb with conventional manual facilitation provided by a physiotherapist, without electrical stimulation. The first module includes Task-Oriented Training of the paretic upper limb, such as reaching, grasping, and object manipulation. When required, assistance to movement is provided manually by the physiotherapist through neuromuscular facilitation techniques, without Functional Electrical Stimulation. The second module consists of conventional physiotherapy focused on joint mobilization and muscle stretching, identical to that delivered in the experimental arm. Each session lasts 60 minutes and is conducted 5 days per week for 2 consecutive weeks (10 sessions total). Receives: Other: Conventional Rehabilitation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Gross Manual Dexterity
Measured as the mean change in score on the Box and Block Test (BBT), defined as the difference in the number of blocks transferred in 60 seconds between baseline and post-treatment
Measured: Baseline (T0, prior to randomization) to Post-Treatment (T1, within 24-48 hours after completion of the 2-week rehabilitation program)
Secondary outcomes (3)
Upper Limb Muscle Strength
Change in upper limb muscle strength measured by the Motricity Index (MI) for the upper limb (score range: 0 to 100, with higher scores indicating greater muscle strength). The MI assesses strength at proximal, middle, and distal joints of the upper limb.
Measured: Baseline (T0, prior to randomization) to Post-Treatment (T1, within 24-48 hours after completion of the 2-week rehabilitation program)
Upper Limb Muscle Tone
Change in muscle tone measured by the Modified Ashworth Scale (MAS) (ordinal scale ranging from 0 to 4, with higher scores indicating greater spasticity), assessed in elbow, wrist, and finger flexor muscles.
Measured: Baseline (T0, prior to randomization) to Post-Treatment (T1, within 24-48 hours after completion of the 2-week rehabilitation program)
Spasticity-related Quality of Life 6-Dimensions (SQoL-6D)
Condition-specific assessment of spasticity-related quality of life. SQoL-6D replaced the originally registered EQ-5D-5L as the quality-of-life outcome.
Measured: Baseline (T0, prior to randomization) to Post-Treatment (T1, within 24-48 hours after completion of the 2-week rehabilitation program)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2026
- Study start1 May 2026
- Primary completion1 Oct 2026 (estimated)
- Study completion1 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for StrokeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Eligible participants are randomized in a 1:1 ratio to one of two parallel intervention groups. One group receives Functional Electrical Stimulation applied to wrist and finger extensor muscles during Task-Oriented Training, while the control group receives Task-Oriented Training with conventional manual facilitation. Both groups undergo the same treatment duration and intensity. Outcomes are assessed by a blinded evaluator at baseline, post-treatment, and follow-up.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Foggia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Spina Stefania, University of Foggia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07513714
- Sponsor's protocol ID
- FoggiaFisiatria02
- Acronym
- ESTIM-UL
- Status last verified
- Mar 2026
- First submitted
- 21 Mar 2026
- Last updated
- 22 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Timmermans AA, Seelen HA, Willmann RD, Kingma H. Technology-assisted training of arm-hand skills in stroke: concepts on reacquisition of motor control and therapist guidelines for rehabilitation technology design. J Neuroeng Rehabil. 2009 Jan 20;6:1. doi: 10.1186/1743-0003-6-1.
PubMed 19154570Lee JM, Gracies JM, Park SB, Lee KH, Lee JY, Shin JH. Botulinum Toxin Injections and Electrical Stimulation for Spastic Paresis Improve Active Hand Function Following Stroke. Toxins (Basel). 2018 Oct 25;10(11):426. doi: 10.3390/toxins10110426.
PubMed 30366407Reebye R, Jacinto LJ, Balbert A, Biering-Sorensen B, Carda S, Draulans N, Molteni F, O'Dell MW, Picelli A, Santamato A, Verduzco-Gutierrez M, Walker H, Wissel J, Francisco GE. Multimodal therapy and use of adjunctive therapies to BoNT-A in spasticity management: defining terminology to help enhance spasticity treatment. Front Neurol. 2024 Aug 30;15:1432330. doi: 10.3389/fneur.2024.1432330. eCollection 2024.
PubMed 39281409Chen HM, Chen CC, Hsueh IP, Huang SL, Hsieh CL. Test-retest reproducibility and smallest real difference of 5 hand function tests in patients with stroke. Neurorehabil Neural Repair. 2009 Jun;23(5):435-40. doi: 10.1177/1545968308331146. Epub 2009 Mar 4.
PubMed 19261767Kwakkel G, van Wegen EEH, Burridge JH, Winstein CJ, van Dokkum LEH, Alt Murphy M, Levin MF, Krakauer JW; ADVISORY group. Standardized Measurement of Quality of Upper Limb Movement After Stroke: Consensus-Based Core Recommendations From the Second Stroke Recovery and Rehabilitation Roundtable. Neurorehabil Neural Repair. 2019 Nov;33(11):951-958. doi: 10.1177/1545968319886477. Epub 2019 Oct 29.
PubMed 31660781Eraifej J, Clark W, France B, Desando S, Moore D. Effectiveness of upper limb functional electrical stimulation after stroke for the improvement of activities of daily living and motor function: a systematic review and meta-analysis. Syst Rev. 2017 Feb 28;6(1):40. doi: 10.1186/s13643-017-0435-5.
PubMed 28245858Picelli A, Santamato A, Chemello E, Cinone N, Cisari C, Gandolfi M, Ranieri M, Smania N, Baricich A. Adjuvant treatments associated with botulinum toxin injection for managing spasticity: An overview of the literature. Ann Phys Rehabil Med. 2019 Jul;62(4):291-296. doi: 10.1016/j.rehab.2018.08.004. Epub 2018 Sep 13.
PubMed 30219307Mills PB, Finlayson H, Sudol M, O'Connor R. Systematic review of adjunct therapies to improve outcomes following botulinum toxin injection for treatment of limb spasticity. Clin Rehabil. 2016 Jun;30(6):537-48. doi: 10.1177/0269215515593783. Epub 2015 Jul 21.
PubMed 26198891Winstein CJ, Stein J, Arena R, Bates B, Cherney LR, Cramer SC, Deruyter F, Eng JJ, Fisher B, Harvey RL, Lang CE, MacKay-Lyons M, Ottenbacher KJ, Pugh S, Reeves MJ, Richards LG, Stiers W, Zorowitz RD; American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, and Council on Quality of Care and Outcomes Research. Guidelines for Adult Stroke Rehabilitation and Recovery: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2016 Jun;47(6):e98-e169. doi: 10.1161/STR.0000000000000098. Epub 2016 May 4.
PubMed 27145936GBD 2016 Stroke Collaborators. Global, regional, and national burden of stroke, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019 May;18(5):439-458. doi: 10.1016/S1474-4422(19)30034-1. Epub 2019 Mar 11.
PubMed 30871944