Non-invasive Brain Stimulation on Functional Capacity in Prefrail Older Adults (NeuroFit)

Effectiveness of Non-invasive Brain Stimulation on Functional Capacity in Prefrail Older Adults

The general objective of this study is to evaluate the effectiveness of non-invasive neuromodulation combined with a therapeutic exercise program on neuroplasticity and, therefore, on variables related to functional capacity and quality of life, in prefrail older adults.

Study Overview

• Status: Not yet recruiting
• Conditions: Prefrail Elderly
• Intervention / Treatment: Other: rTMS; Other: rTMS placebo; Other: tDCS; Other: tDCS placebo; Other: Virtual running; Other: Virtual running placebo

Detailed Description

Three non-invasive neuromodulation strategies (Virtual Running, Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS)) will be studied. Thus, 3 sub-studies will be carried out (one for each intervention) and a comparison of the three interventions will be made, as described in the following sections. As specific objectives, for each of these sub-studies, the effect of the intervention program will be analyzed on: gait speed, general physical condition, frailty condition, static and dynamic functionality and gait quality, upper limb and lower limb isometric strength, quality of life, and neuroplasticity, in terms of plasma BDNF levels, in prefrail older adults.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Marta Inglés de la Torre, PHD; Phone Number: (9638) 64003; Email: marta.ingles@uv.es

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age between 65 -90 years old
• Meet 1-2 frailty criteria, according to Fried's Criteria.
• Ability to understand instructions (Mini-Mental State Examination >23 points).
• Signing of the informed consent.

Exclusion Criteria:

• History of stroke within the past 6 months or hospital admission for any reason within the past 3 months.
• Alterations of the central or peripheral nervous system
• Alterations of the vestibular system
• Concomitant diseases
• Have a neurological pathology, cardiovascular musculoskeletal that contraindicates physical activity
• Epilepsy or history, medications that lower the seizure threshold
• Cardiac pacemaker, endocranial and hearing implants
• History of severe headaches
• Uncontrolled intracranial or arterial hypertension
• Heart and/or respiratory failure
• Implanted medication pump
• Skin lesions (psoriasis, eczema)
• Serious head surgeries
• Completing less than 80% of training sessions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VR group	Other: Virtual running; 24 sessions will be applied, 3 days a week. The patient will be placed standing (with an ad-hoc designed assistance system) in front of a mirror (located at waist height) and a height-adjustable screen (from waist to caudal) where a video of real legs running on a treadmill will be projected. In order for the participant to feel the projected legs as their own, people with different body sizes will have been previously recorded running to have recordings with legs of different size and length. Each session will last 20 minutes. They will then perform the therapeutic exercise protocol explained above.
Experimental: rTMS group	Other: rTMS; 24 HF-TMS sessions, 3 per week, with a duration of 20 minutes. Magnetic stimulation will be applied using a Neuro-MS/D transcranial magnetic stimulator (Neurosoft ®, Ivanovo, Russia) with a figure-eight coil. The coil will be placed tangentially to the skull in an anteromedial direction at 45º of M1 in the left hemisphere. They will then carry out a therapeutic exercise protocol (common to all groups) that will consist of performing lower limb exercises, including coordination, strength, balance and stretching exercises. The Borg Scale will be used to measure each person's perception of their effort, dyspnea and fatigue during each physical exercise.
Experimental: tDCS group	Other: tDCS; The tDCS will be performed anodically (a-tDCS), and for 24 sessions, 3 days a week. The electrodes will be mounted on a neoprene helmet, in accordance with the International Standard 10-20 EEG System, for optimal targeting of the primary motor cortex M1. It will be a type of unihemispheric application, in which the anode will be located in the primary motor cortex (M1), and the cathode located in the orbitofrontal cortex contralateral to the anode. The treatment parameters will be: stimulation time of 20 minutes; intensity of 2mA, current rise-fall time at the beginning and end of stimulation of 30 seconds. They will then perform the therapeutic exercise protocol explained above.
Placebo Comparator: rTMS placebo group	Other: rTMS placebo; The instrumentation will be the same as in the intervention with real rTMS, but the device will not emit any type of electrical stimulus. They will then perform the therapeutic exercise protocol explained above
Placebo Comparator: tDCS placebo group	Other: tDCS placebo; The instrumentation will be the same as in the actual tDCS intervention, but the device will be programmed to increase the intensity from 0 to 2 mA progressively during the first 30 seconds and then cease to provide the patient with the initial itchy sensation on the skin, similar to the real application. They will then perform the therapeutic exercise protocol explained above.
Placebo Comparator: VR placebo group	Other: Virtual running placebo; The instrumentation of the participants will be the same as in the intervention with virtual running. However, the projection will consist of a series of videos of landscapes in which no type of human or animal movement will appear in order not to stimulate the motor areas of the brain. They will then perform the therapeutic exercise protocol explained above.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frailty Condition	Fried's criteria (Frailty Phenotype) will be used. Briefly, the participant will be considered frail if he or she meets three or more of the following criteria: i) unintentional weight loss greater than 4.5 kg in the last year; ii) feeling of general exhaustion, reported by the patient himself; iii) low level of physical activity; (iv) slowness of progress; v) muscle weakness, assessed by handgrip strength. Those patients who meet one or two criteria will be considered pre-frail and those who do not meet either will be considered non-frail	Five assessments: Baseline (T1); After the first session, at Day 1 (T2); Mid-term assessment, 4 weeks after the intervention starts (T3); After the intervention, 8 weeks (T4); Four weeks after the end of the intervention (follow-up assessment) (T5).
Walking speed	The 10m Walking Test will be used to assess the speed of the walk, which records the time needed to cover the distance of 10m. The higher the walking speed, the greater the functional capacity	Five assessments: Baseline (T1); After the first session, at Day 1 (T2); Mid-term assessment, 4 weeks after the intervention starts (T3); After the intervention, 8 weeks (T4); Four weeks after the end of the intervention (follow-up assessment) (T5).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuroplasticity	Neruoplasticity will be determined from the concentration of BDNF in plasma. A nurse will draw blood samples in BD Vacutainer® tubes, with EDTA as an anticoagulant. It will be centrifuged at 1500 G for 15 minutes at 4⁰ C, the supernatant (plasma) will be collected in eppendorf type tubes, which will be frozen at -80⁰ C until subsequent analysis. For the determination of BDNF levels, the ChemiKine™ BDNF Sandwich kit for ELISA (Millipore, Temecula, CA, USA) will be used, according to the manufacturer's instructions	Three assessments: Baseline (T1); After the intervention, 8 weeks (T4); Four weeks after the end of the intervention (follow-up assessment) (T5).
Heart rate variability	HRV will be measured during 5 minutes at rest before intervention and during 20 minutes while performing aerobic exercise (walking). HRV will be measured with the PolarH10 band (Polar ®, Finland).	Five assessments: Baseline (T1); After the first session, at Day 1 (T2); Mid-term assessment, 4 weeks after the intervention starts (T3); After the intervention, 8 weeks (T4); Four weeks after the end of the intervention (follow-up assessment) (T5).
Muscle strength	Measurement of the isometric action of the lower limb muscles will be carried out by means of a load cell (Chronojump, Spain) connected to the corresponding software (Chronojump Boscosystem). Specifically, the isometric strength of the gluteus medius, quadriceps, and hamstrings will be measured. The participant will be asked for a maximum of three repetitions with a duration of five seconds each, and a rest between them of another thirty seconds. The maximum value will be recorded, as well as the average value of each of the three repetitions, and the average will then be obtained, which will be the variable used for the subsequent data analysis. As for upper limb strength, assessed by grip strength, this will be determined by a Lafayette hand dynamometer. 3 measurements of the dominant hand will be taken and the mean will be taken for further analysis. Higher values indicate greater muscle strength	Three assessments: Baseline (T1); After the intervention, 8 weeks (T4); Four weeks after the end of the intervention (follow-up assessment) (T5).
Quality of life EQ-5D	Determined using the EQ-5D instrument, a measure of self-perceived health, consisting of two parts: the EQ-5D descriptive system, which assesses five dimensions of health (i.e. mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and a visual analogue scale (VAS), in which people must estimate their general health status on a scale from 0 to 100. Higher values indicate greater quality of life.	Three assessments: Baseline (T1); After the intervention, 8 weeks (T4); Four weeks after the end of the intervention (follow-up assessment) (T5).
Lower limb muscle power	It will be recorded with the 5 times sit to stand test (5STST). The participant must sit down and get up from a chair and the time it takes to perform the activity is timed. The higher the speed, the greater lower limb power	Five assessments: Baseline (T1); After the first session, at Day 1 (T2); Mid-term assessment, 4 weeks after the intervention starts (T3); After the intervention, 8 weeks (T4); Four weeks after the end of the intervention (follow-up assessment) (T5).
Static and dynamic functionality and gait quality	For this assessment, the FallSkip® tool will be used, which allows, by means of an inertial sensor incorporated in a smartphone, to record variables such as the medium-lateral and vertical displacement of the center of pressures in both dynamic and static, as well as to record the power to sit and get up from a chair and the variability of movement in a modified protocol of the Timed up and Go test. Based on the calculation of these variables, FallSkip® provides a fall risk score for each patient, ranging from very low, low, moderate, high, to very high risk, depending on the results obtained during the different test phases.	Five assessments: Baseline (T1); After the first session, at Day 1 (T2); Mid-term assessment, 4 weeks after the intervention starts (T3); After the intervention, 8 weeks (T4); Four weeks after the end of the intervention (follow-up assessment) (T5).
Static and dynamic functionality and gait quality with a dual task	For this assessment, the FallSkip® tool will be used, which allows, by means of an inertial sensor incorporated in a smartphone, to record variables such as the medium-lateral and vertical displacement of the center of pressures in both dynamic and static, as well as to record the power to sit and get up from a chair and the variability of movement in a modified protocol of the Timed up and Go test. Based on the calculation of these variables, FallSkip® provides a fall risk score for each patient, ranging from very low, low, moderate, high, to very high risk, depending on the results obtained during the different test phases. For the dual task, a simultaneous activity will be used that will consist of numerical subtraction while walking. The higher punctuation, the better dual task functionality.	Three assessments: Baseline (T1); After the intervention, 8 weeks (T4); Four weeks after the end of the intervention (follow-up assessment) (T5).

Collaborators and Investigators

• Sponsor: University of Valencia

Publications and helpful links

General Publications

• Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA; Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001 Mar;56(3):M146-56. doi: 10.1093/gerona/56.3.m146.
• Global Recommendations on Physical Activity for Health. Geneva: World Health Organization; 2010. Available from http://www.ncbi.nlm.nih.gov/books/NBK305057/
• Molla-Casanova S, Page A, Lopez-Pascual J, Ingles M, Sempere-Rubio N, Aguilar-Rodriguez M, Munoz-Gomez E, Serra-Ano P. Effects of mirror neuron activation therapies on functionality in older adults: Systematic review and meta-analysis. Geriatr Nurs. 2024 Mar-Apr;56:115-123. doi: 10.1016/j.gerinurse.2024.02.006. Epub 2024 Feb 11.

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: December 3, 2025
• First Submitted That Met QC Criteria: January 7, 2026
• First Posted (Estimated): January 16, 2026

Study Record Updates

• Last Update Posted (Estimated): January 16, 2026
• Last Update Submitted That Met QC Criteria: January 7, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Elderly; TMS; Functional capacity; TDCS; Non-invasive neuromodulation; Prefrail; Virtual running
• Additional Relevant MeSH Terms: Therapeutics; Behavioral Disciplines and Activities; Electric Stimulation Therapy; Convulsive Therapy; Psychiatric Somatic Therapies; Electroshock; Psychological Techniques; Transcranial Direct Current Stimulation
• Other Study ID Numbers: 2025-FIS-4007899

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: IPD will be shared under request to the authors

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No