Study Evaluating the Effect of Transcranial Direct Current Stimulation (tDCS) Targeting the Right Inferior Frontal Gyrus on Inhibitory Control in Patients With PSP

NCT07818733 | Not Yet Recruiting

• 1 other identifier: RC23_0119
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease with a prevalence estimated at 6 per 100,000 in France and a rapidly progressive course. In its classic form (known as the Richardson type), it presents with a predominantly axial Parkinsonian syndrome, postural instability with early falls, oculomotor disorders, and cognitive and behavioral disturbances. Apart from levodopa, which may provide a modest improvement in Parkinsonian syndrome in some patients, the current therapeutic approach relies primarily on rehabilitation techniques, with no proven efficacy. Cognitive-behavioral symptoms are common in this disease and are primarily characterized by impaired executive functions, linked to dysfunction of the frontal cortex. They often have a devastating effect on quality of life, are associated with an increased risk of falls, and represent a considerable burden for caregivers. Among these symptoms, apathy is the most commonly described symptom. Impulsivity, associated with impaired inhibitory control, is present in 32-74% of cases and may coexist with apathy. Cognitive and behavioral inhibition depends on a complex brain network that includes, among others, the right inferior frontal gyrus (IFG), the dorsolateral prefrontal cortex, the supplementary motor area, the motor cortex, and the basal ganglia. It has recently been shown that patients with PSP have impaired functional connectivity between the right LFC and other brain structures in the network, and that neurotransmitter deficits in the right LFC correlate with their impulsivity Alongside pharmacological approaches, non-invasive brain stimulation techniques are rapidly expanding as a potential therapeutic tool. Transcranial direct current stimulation (tDCS), by modulating cortical excitability, is a promising technique. It is simple to administer and has demonstrated efficacy in several clinical settings. Furthermore, a recent meta-analysis of 45 clinical studies shows that single or repeated tDCS sessions could modestly but significantly improve the inhibitory response-measured by reaction time in the stop-signal paradigm-especially when active (anodal) stimulation was applied to the right GFI. These studies primarily involved healthy subjects. A few studies have examined the effects of tDCS in neurodegenerative diseases and in PSP. These studies are still preliminary, involving small sample sizes, but are encouraging. Among these, a randomized study comparing tDCS to sham tDCS demonstrated a beneficial effect of a single-session tDCS session targeting the dorsolateral prefrontal cortex on verbal fluency in patients with PSP. The hypothesis of our study is that applying tDCS stimulation over the right GFI will improve certain cognitive functions and reduce behavioral impulsivity in patients. Very little data on tDCS in PSP is available to date. Only three studies have been published. With very different designs-including only one randomized trial comparing tDCS to sham tDCS-these studies evaluated the effects of tDCS applied to the dorsolateral prefrontal cortex or to motor and premotor areas on language and motor symptoms, respectively. In this randomized, double-blind, controlled study, the investigators propose to explore the effects of tDCS on the right GFI on executive functions and, more specifically, on inhibitory control. Another strength of our study is that only patients with proven frontal cerebral hypometabolism on FDG-PET-MRI will be included, which will allow us to test the effect of tDCS on a clearly dysfunctional neural network. Furthermore, as a secondary objective, the investigators will be able to assess whether the effects of tDCS depend on the intensity and/or topography of cerebral hypometabolism. The neurophysiological effects of a single tDCS session appear to last up to 60 to 90 minutes. In this proof-of-concept study, the assessment tests were deliberately chosen for their short administration time and low test-retest effect. Finally, the Stop Signal Test, already used in this population, is widely used and well-standardized. This pilot study will provide initial data on the cognitive and motor effects of a tDCS session on the GFI, with a focus on inhibition. Given the limited effectiveness of symptomatic treatments-particularly pharmacological ones-having a new option capable of improving cognitive and/or behavioral performance would have a significant impact on the quality of life of patients and their families. tDCS has the advantage of being easily accessible and generally well-tolerated by patients and could eventually be administered in patients' homes. If our study demonstrates an improvement in certain cognitive/motor functions, it would lead to a larger-scale study with repeated sessions to assess its benefits over a longer period. Finally, if an improvement in executive functions is demonstrated in PSP, this could apply to other neurodegenerative diseases.

Conditions

PSP - Progressive Supranuclear Palsy

Keywords

PSP; Progressive Supranuclear Palsy; Transcranial direct current stimulation (tDCS); GFI

Outcome Measures

Primary Outcomes (1)

• To evaluate the effect of anodal tDCS targeting the right inferior frontal gyrus (IFG) on a motor-modality cognitive inhibition task, the Stop Signal Task (SST), in patients with PSP.

  Stop Signal Reaction Time (SSRT) during the SST (seconds)

  during the hour before each tDCS session and within 1 hour after each tDCS session

Secondary Outcomes (15)

• To evaluate, in PSP, the effect of anodal tDCS targeting the right GFI on the components of cognitive inhibition assessed by the SST

  during the hour before each tDCS session and within 1 hour after each tDCS session

• To evaluate, within the PSP, the effect of anodal tDCS targeting the right GFI on scores on the following neuropsychological assessments of verbal cognitive inhibition

  during the hour before each tDCS session and within 1 hour after each tDCS session

• To evaluate, within the PSP, the effect of anodal tDCS targeting the right GFI on scores on the following neuropsychological assessments of perseverative motor behavior

  during the hour before each tDCS session and within 1 hour after each tDCS session

• To evaluate, within the PSP, the effect of anodal tDCS targeting the right GFI on scores on the following neuropsychological assessments of other executive functions

  during the hour before each tDCS session and within 1 hour after each tDCS session

• To evaluate, within the PSP, the effect of anodal tDCS targeting the right GFI on scores on the following neuropsychological assessments of social cognition

  during the hour before each tDCS session and within 1 hour after each tDCS session

Study Arms (2)

tDCS Active (first visit) + tDCS sham (second visit)

OTHER

Each participant will receive active tDCS then sham tDCS during two 20-minute sessions spaced one month apart

Device: tDCS, or transcranial direct current stimulation

sham tDCS (fist visit) + active tDCS (second visit)

OTHER

Each participant will receive sham tDCS then active tDCS during two 20-minute sessions spaced one month apart

Device: tDCS, or transcranial direct current stimulation

Interventions

tDCS, or transcranial direct current stimulation DEVICE

Each participant will receive both active tDCS and sham tDCS during two 20-minute sessions spaced one month apart, with the order of the sessions determined at random.

sham tDCS (fist visit) + active tDCS (second visit); tDCS Active (first visit) + tDCS sham (second visit)

Eligibility Criteria

• Age: 40 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 40 to 89 years
• Patients with probable PSP according to the MDS-9 diagnostic criteria
• BREF score \>10;
• FDG PET-MRI performed no more than 6 months prior to enrollment and showing:
• Glucose hypometabolism defined as \> 2.5 SD compared to an atlas of healthy subjects and
• No severe right frontal cortical atrophy according to F Pasquier's global cortical atrophy scale 53
• Concomitant treatments must have been stable for at least 4 weeks prior to enrollment and must remain stable throughout participation
• Patient must have provided written informed consent
• Patient must be enrolled in a social security program
• Patient must be able to understand French and comply with the protocol
• Women must use adequate contraceptive measures for the duration of the clinical trial (in accordance with CTFG recommendations)

You may not qualify if:

• Left-handed Patients;
• Patients with severe apraxia that interferes with performance of the SST (at the investigator's discretion)
• Known visual or hearing impairment that prevents performance of cognitive tests or the stop-signal test;
• History of severe psychiatric or neurological disorders other than PSP;
• Known significant brain injury(ies) (stroke, tumor, inflammation, post-traumatic, etc.), at the investigator's discretion
• Atrophy of the right frontal lobe ≥3 on the F Pasquier Global Cortical Atrophy Scale 53
• History of epilepsy and seizures (or cerebral impairment with unexplained loss of consciousness), severe cardiac disorders, neurosurgical procedures, or severe or frequent headaches;
• Presence of a cardiac, neural, drug-delivery, or cerebral stimulator
• Presence of cerebral medical devices (such as vascular clips or electronically sensitive devices), intracerebral or intracochlear metal implants,
• Patients with any electrically, magnetically, or mechanically activated implant
• Patients suffering from a serious, life-threatening condition such as congestive heart failure, chronic obstructive pulmonary disease (COPD), or active neoplasia
• Patients with skin conditions (dermatitis, psoriasis, or eczema) or lesions on the scalp or skull that preclude tDCS
• Patients under legal guardianship or protective supervision
• Pregnant or breastfeeding women
• For patients in the ancillary study, contraindication to MRI: Presence of metallic foreign bodies

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (1)

CHU de Nantes

Nantes, Loire Atlantique, 44093, France

Location

MeSH Terms

Conditions

Supranuclear Palsy, Progressive

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Ophthalmoplegia; Ocular Motility Disorders; Cranial Nerve Diseases; Tauopathies; Neurodegenerative Diseases; Paralysis; Neurologic Manifestations; Eye Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Central Study Contacts

Anne-Gaëlle Dr CORBILLE

CONTACT

0240165967; ANNEGAELLE.CORBILLE@chu-nantes.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2026
• First Posted: September 14, 2026
• Study Start: September 15, 2026
• Primary Completion (Estimated): July 15, 2028
• Study Completion (Estimated): July 15, 2028
• Last Updated: September 14, 2026

Record last verified: 2026-09

Locations

FR (1)