Effects of tVNS and mCIMT in Chronic Stroke

NCT07272239 | Recruiting DMC

• 1 other identifier: REC/0270 Zara Mansha
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

Stroke is a leading cause of death and disability worldwide, resulting in significant physical and cognitive impairments. Arm weakness is most common after stroke and its treatment is recognized as an area of considerable need. The functional limitations and disabilities experienced by stroke survivors, particularly in the upper limb have a profound impact on their quality of life. Current treatment for arm weakness typically comprises intensive, task-specific and repetitive rehabilitative interventions. Transcutaneous auricular vagus nerve stimulation (tVNS) is a novel noninvasive treatment for stroke that directly stimulates the peripheral auricular branch of the vagus nerve. This study determines the effects of Vagus Nerve Stimulation and Modified Constraint Induced Movement Therapy on Motor Function, Cognition, and Quality of life in chronic stroke patients. This randomized clinical trial will be conducted at IIMCT Railway General Hospital and Al-firdous physiotherapy clinic over a duration of six months. The sample size will consist of 50 participants. Participants which meet the inclusion criteria will be taken through non-probability convenience sampling technique, which will further be randomized through online randomization tool. 25 Participants will be assigned to Group A receiving tVNS and mCIMT with routine physical therapy and 25 to Group B receiving mCIMT with routine physical therapy . Data will be collected using various assessment tools, including Fugl-Meyer Assessment-UE (FM-UE), and Nine-hole peg test (NHPT) to assess Motor function. Stroke Impact Scale (SIS) to assess QOL, Montreal cognitive assessment (MoCA) to assess cognition, and Modified Ashworth scale to assess spasticity. All participants will receive intervention 3 days a week on alternative days for 8 weeks. Pre-intervention assessments will be conducted for both groups. The effects of the interventions will be measured at pre-treatment, 4th week, and post-intervention. Data analysis will be performed by using SPSS 26 software. Key words: Modified Constraint Induced movement Therapy, Motor function, Rehabilitation, Stroke, Transcutaneous Vagus nerve stimulation, Upper extremity.

Conditions

Stroke; Cerebrovascular Accident

Keywords

Vagus Nerve Stimulation; Motor Function; Modified Constraint Induced Movement Therapy; Upper Limb Function

Outcome Measures

Primary Outcomes (4)

• Fugl- Meyer Assessment- UE (FM-UE)

  The Fugl-Meyer Assessment of Upper Extremity (FMA-UE) is a reliable and valid tool for evaluating upper limb function in stroke patients. Comprising 33 items, it assesses motor function, sensory function, and joint mobility. The FMA-UE demonstrates excellent intra-rater (ICC \> 0.90) and inter-rater reliability (median agreement \~77%). It correlates well with other measures, showing strong construct validity and responsiveness, making it essential for tracking recovery in rehabilitation settings.

  Assessment will be done at baseline, 4th and 8th week of intervention

• Nine- hole peg test (NHPT)

  The Nine-Hole Peg Test (NHPT) is a widely used assessment tool for measuring manual dexterity and fine motor skills, particularly in clinical populations such as stroke and multiple sclerosis patients. The test involves placing and removing nine pegs from a pegboard as quickly as possible, with the time taken recorded in seconds. Reliability is strong, with intraclass correlation coefficients (ICCs) ranging from 0.91 to 0.94 for individuals with stroke and 0.49 to 0.66 for healthy adults, indicating good relative reliability. Validity is supported by its ability to discriminate between varying levels of impairment and its correlation with other dexterity measures, confirming its effectiveness in clinical settings.

  Assessment will be done at baseline, 4th and 8th week of intervention

• Montreal cognitive assessment (MoCA)

  The Montreal Cognitive Assessment (MoCA) is a widely utilized screening tool developed by Dr. Ziad Nasreddine in 1996 to detect cognitive impairment, particularly mild cognitive impairment (MCI) and early Alzheimer's disease. The test takes about 10 minutes and evaluates multiple cognitive domains, including memory, attention, language, executive function, and visuospatial abilities. MoCA has shown high reliability (ICC = 0.92) and good internal consistency (Cronbach's alpha = 0.82). Its sensitivity for detecting MCI is 90%, with a specificity of 87% compared to the Mini-Mental State Examination (MMSE).

  Assessment will be done at baseline, 4th and 8th week of intervention

• Stroke impact scale (SIS)

  The Stroke Impact Scale (SIS) is a patient-reported outcome measure designed to evaluate the effects of stroke on various aspects of life, including physical, emotional, and social domains. Developed by Duncan et al. in 1999, the SIS assesses eight dimensions: strength, hand function, mobility, activities of daily living, emotion, memory, communication, and social participation. The scale produces scores ranging from 0 to 100, with higher scores indicating better function. It has demonstrated excellent reliability (Cronbach's alpha = 0.83 to 0.95) and validity in predicting quality of life post-stroke.

  Assessment will be done at baseline, 4th and 8th week of intervention

Secondary Outcomes (1)

• Modified Ashworth Scale (MAS)

  Assessment will be done at baseline, 4th and 8th week of intervention

Study Arms (2)

Group A

EXPERIMENTAL

Transcutaneous Vagus Nerve Stimulation and Modified Constraint Induced Movement Therapy with Routine Physical Therapy

Device: Transcutaneous Vagus Nerve Stimulation; Other: Modified Constraint Induced Movement Therapy with Routine Physical Therapy

Group B

EXPERIMENTAL

Modified Constraint Induced Movement Therapy with Routine Physical Therapy

Other: Modified Constraint Induced Movement Therapy with Routine Physical Therapy

Interventions

Transcutaneous Vagus Nerve Stimulation DEVICE

Each treatment session will last one hour, conducted three times per week on alternate days for eight weeks. The session will begin with 30 minutes of routine physical therapy, which will include active and active-assisted range of motion exercises, strengthening and coordination activities, and functional task training for the upper extremity. The following 30 minutes will include concurrent tVNS and mCIMT. tVNS will be administered through surface electrodes placed on the auricular region (tragus or cymba conchae) of the ear, with stimulation parameters set at a frequency of 25 Hz, pulse width of 250 μs, and intensity adjusted to a comfortable tingling level below the pain threshold. During this period, participants will perform task-oriented activities of the affected upper limb through functional tasks such as reaching, grasping, and object manipulation. Shaping techniques will be used to progressively increase task difficulty, and a soft mitt applied to the unaffected hand.

Group A

Modified Constraint Induced Movement Therapy with Routine Physical Therapy OTHER

Participants will also receive session lasting for one hour, with 30 minutes devoted to routine physical therapy followed by 30 minutes of mCIMT. The routine physical therapy component will include range of motion exercises, stretching, strengthening, and functional movement training similar to Group A to ensure treatment uniformity. The 30-minute mCIMT intervention will consist of intensive, task-specific practice of the affected upper limb under therapist supervision, focusing on goal-oriented functional tasks and repetitive training to enhance motor performance. A shaping approach will be used to progressively increase task complexity based on individual capability, and a soft constraint applied to the unaffected limb during the session.

Group A; Group B

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Both male and female patients are included in the study.
• Left sided ischemic stroke patients.
• Patients with chronic, moderate-severe upper limb hemiparesis (\>6 months-2 years)
• Stable participants having a stroke severity score \> 6 on National Institute of Health Stroke Scale (NIHSS).
• Montreal Cognitive Assessment (MoCA) score ≥26.

You may not qualify if:

• Participants who show the symptoms of global or receptive aphasia.
• Participants who have a history of significant neurological or psychiatric disorders, other than stroke, that could interfere with upper limb motor or sensory recovery.
• Modified Ashworth scale score ≥ 3 of the affected upper extremity.
• Patients who are not able to sit with or without support.
• Patients with severe apraxia, somatosensory problems.
• Resting heart rate (\< 50 beats/min).
• Participants who are currently participating in another clinical trial or research study.

Sponsors & Collaborators

• Riphah International University: lead

Study Sites (2)

Al- firdous physiotherapy clinic

Rawalpindi, Punjab Province, 46000, Pakistan

RECRUITING

IIMCT- Railway General Hospital

Rawalpindi, Punjab Province, 46000, Pakistan

RECRUITING

Related Publications (5)

• Page SJ, Sisto S, Levine P, McGrath RE. Efficacy of modified constraint-induced movement therapy in chronic stroke: a single-blinded randomized controlled trial. Arch Phys Med Rehabil. 2004 Jan;85(1):14-8. doi: 10.1016/s0003-9993(03)00481-7.

  PMID: 14970962 BACKGROUND

• Hays SA. Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation. Neurotherapeutics. 2016 Apr;13(2):382-94. doi: 10.1007/s13311-015-0417-z.

  PMID: 26671658 BACKGROUND

• Redgrave J, Day D, Leung H, Laud PJ, Ali A, Lindert R, Majid A. Safety and tolerability of Transcutaneous Vagus Nerve stimulation in humans; a systematic review. Brain Stimul. 2018 Nov-Dec;11(6):1225-1238. doi: 10.1016/j.brs.2018.08.010. Epub 2018 Aug 23.

  PMID: 30217648 BACKGROUND

• Dawson J, Pierce D, Dixit A, Kimberley TJ, Robertson M, Tarver B, Hilmi O, McLean J, Forbes K, Kilgard MP, Rennaker RL, Cramer SC, Walters M, Engineer N. Safety, Feasibility, and Efficacy of Vagus Nerve Stimulation Paired With Upper-Limb Rehabilitation After Ischemic Stroke. Stroke. 2016 Jan;47(1):143-50. doi: 10.1161/STROKEAHA.115.010477. Epub 2015 Dec 8.

  PMID: 26645257 BACKGROUND

• Khodaparast N, Hays SA, Sloan AM, Hulsey DR, Ruiz A, Pantoja M, Rennaker RL 2nd, Kilgard MP. Vagus nerve stimulation during rehabilitative training improves forelimb strength following ischemic stroke. Neurobiol Dis. 2013 Dec;60:80-8. doi: 10.1016/j.nbd.2013.08.002. Epub 2013 Aug 15.

  PMID: 23954448 BACKGROUND

MeSH Terms

Conditions

Stroke

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Aruba Saeed, Phd

  Riphah International University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zara Mansha, Ms-Nmpt

CONTACT

+923247502192; zaramansha09@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2025
• First Posted: December 9, 2025
• Study Start: November 25, 2025
• Primary Completion: May 5, 2026
• Study Completion: May 5, 2026
• Last Updated: December 9, 2025

Record last verified: 2025-12

Locations

PA (2)