Clinical trial NCT06885138: Clinical and Neurophysiological Effects of tDCS on Depression in Parkinson's Disease
Official title: Study of the Clinical and Neurophysiological Effects of Transcranial Direct Current Stimulation on Depressive Symptoms in Parkinson's Disease.
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: PARKINSON DISEASE (Disorder)
Keywords: Depression
Parkinson Disease
tDCS
Lead sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Sponsor class: OTHER
First posted: 2025-03-20
Enrollment: 52
Sex: ALL
Minimum age (years): 35
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Parkinson's disease (PD) is the second most common neurodegenerative disorder, characterized by dopaminergic cell degeneration leading to neurophysiological alterations and a heterogeneous clinical presentation. In addition to motor symptoms, PD patients often experience non-motor symptoms, particularly neuropsychiatric manifestations such as depression, anxiety, and apathy. Depression is one of the most prevalent behavioral symptoms, affecting at least 50% of PD patients, with a higher incidence compared to the general population and other disabling conditions. Two main hypotheses explain the emergence of depressive symptoms: one considers depression a reactive response to progressive disability, while the other links it to the underlying neurobiological mechanisms of PD. Additionally, depression and anxiety frequently co-occur in PD, suggesting shared neurobiological pathways.

Conventional pharmacological treatments only partially address affective symptoms in PD, highlighting the need for innovative non-pharmacological therapies. Transcranial direct current stimulation (tDCS) has gained attention as a potential treatment, showing promising results in improving both motor and affective symptoms in PD. While preliminary studies suggest that tDCS may significantly reduce depressive symptoms, current evidence is insufficient to establish clinical recommendations, necessitating further large-scale, randomized controlled trials.

Objectives

The primary objective of this study is to evaluate the effects of repeated tDCS sessions on depressive symptoms in PD patients. Secondary objectives include:

* Assessing the potential impact of repeated tDCS sessions on anxiety, apathy, sleep quality, and quality of life in PD patients.
* Investigating the neurophysiological mechanisms underlying depression and the effects induced by tDCS.

Methodology

Eligible patients will be randomly assigned to one of two groups:

1. Experimental Group: Patients will receive repeated sessions of active tDCS (anodal stimulation). The active electrode (35 cm²) will be placed over the left dorsolateral prefrontal cortex (DLPFC), with the reference electrode (35 cm²) on the contralateral area. Stimulation intensity will be set at 2mA, and each session will last 20 minutes.
2. Control Group: Patients will receive sham tDCS sessions. Electrodes will be positioned identically to the active condition, but the current will only be applied for the first 5 seconds to prevent perception of the sham condition while ensuring no neuromodulatory effects. Each session will last 20 minutes.

Both groups will undergo tDCS sessions on days 1, 2, 3, 4, 5, 12, 19, and 26 of the study.

Assessment and Outcome Measures tDCS treatment will be administered in a hospital setting using the Newronika stimulator (CE-certified medical device). The effects on depressive symptoms and neurophysiological mechanisms will be evaluated using validated clinical scales and neurophysiological assessments at multiple time points:

* T0 (Day 1): Baseline assessment before treatment initiation.
* T1 (Day 5): After one week of treatment.
* T5 (Day 33): One week after completing all treatment sessions.
* T6 (Day 54): One month after treatment completion.

This study aims to improve the understanding of tDCS's clinical efficacy and underlying mechanisms in managing affective symptoms in PD. The findings could support the development of evidence-based non-pharmacological interventions for PD patients.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of idiopathic Parkinson's disease according to the clinical diagnostic criteria of the Movement Disorder Society;
* No dementia (Montreal Cognitive Assessment score ≥ 22/30);
* Presence of depressive symptoms
* Pharmacological treatment for motor symptoms stable for at least 1 month
* Treatment (pharmacological/non-pharmacological) for depressive symptoms stable for at least 3 months.

Exclusion Criteria:

* Patients with a pacemaker, intracranial electrodes, implanted defibrillators, or any other type of prosthesis;
* Patients undergoing Deep Brain Stimulation treatment;
* Patients with epilepsy or a history of seizures;
* Patients with psychosis;
* Patients with a history of skull fracture;
* Pregnant/breastfeeding patients;
* Patients with suicidal ideation or a suicide attempt in the six months prior to the start of the study;
* Patients with a history of substance dependence or abuse;
* Concomitant treatment with medications that may affect tDCS (benzodiazepines, anticonvulsants, pseudoephedrine, dextromethorphan).

Primary outcomes:
measure: Beck Depression Inventory-II (BDI-II)
timeFrame: Baseline (T0); on day 5 (T1); one week after the end of treatment on day 33 (T2); one month after the end of treatment on day 54 (T3)
measure: Montgomery-Åsberg Depression Rating Scale (MADRS)
timeFrame: Baseline (T0); on day 5 (T1); one week after the end of treatment on day 33 (T2); one month after the end of treatment on day 54 (T3)
measure: Visual Analog Scale (VAS)
timeFrame: Baseline (T0); on day 5 (T1); one week after the end of treatment on day 33 (T2); one month after the end of treatment on day 54 (T3)
Secondary outcomes:
measure: State-Trait Anxiety Inventory (STAI)
timeFrame: Baseline (T0); on day 5 (T1); one week after the end of treatment on day 33 (T2); one month after the end of treatment on day 54 (T3)
measure: Apathy Evaluation Scale (AES)
timeFrame: Baseline (T0); on day 5 (T1); one week after the end of treatment on day 33 (T2); one month after the end of treatment on day 54 (T3)
measure: Parkinson's Disease Questionnaire-8 (PDQ-8)
timeFrame: Baseline (T0); on day 5 (T1); one week after the end of treatment on day 33 (T2); one month after the end of treatment on day 54 (T3)
measure: Pittsburgh Sleep Quality Index (PSQI)
timeFrame: Baseline (T0); on day 5 (T1); one week after the end of treatment on day 33 (T2); one month after the end of treatment on day 54 (T3)
measure: EEG Peak Frequency in the Beta Band (Hz)
timeFrame: Baseline (T0); on day 5 (T1); one week after the end of treatment on day 33 (T2); one month after the end of treatment on day 54 (T3)
measure: Blink Reflex Area (mV·ms)
timeFrame: Baseline (T0); on day 5 (T1); one week after the end of treatment on day 33 (T2); one month after the end of treatment on day 54 (T3)
measure: Blink Reflex Duration (ms)
timeFrame: Baseline (T0); on day 5 (T1); one week after the end of treatment on day 33 (T2); one month after the end of treatment on day 54 (T3)
measure: Blink Reflex Latency (ms)
timeFrame: Baseline (T0); on day 5 (T1); one week after the end of treatment on day 33 (T2); one month after the end of treatment on day 54 (T3)
measure: Startle Saccadic Reflex Area (mV·ms)
timeFrame: Baseline (T0); on day 5 (T1); one week after the end of treatment on day 33 (T2); one month after the end of treatment on day 54 (T3)
measure: Startle Saccadic Reflex Duration (ms)
timeFrame: Baseline (T0); on day 5 (T1); one week after the end of treatment on day 33 (T2); one month after the end of treatment on day 54 (T3)
measure: Startle Saccadic Reflex Latency (ms)
timeFrame: Baseline (T0); on day 5 (T1); one week after the end of treatment on day 33 (T2); one month after the end of treatment on day 54 (T3)
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Study officials:
References: