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.

Overview

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.

Interventions

• Device active transcranial Direct Current Stimulation
  Patients will undergo repeated sessions of active transcranial Direct Current Stimulation (tDCS) (anodal polarity). The active electrode (35 cm²) will be placed over the left dorsolateral prefrontal cortex (DLPFC), while the reference electrode (35 cm²) will be positioned over the contralateral area, with a stimulation intensity of 2mA. Patients will undergo a tDCS session on days 1, 2, 3, 4, 5, 12, 19, and 26 of the study. Each session will last 20 minutes.
• Device sham transcranial Direct Current Stimulation
  Patients will undergo repeated sessions of "sham tDCS." The electrodes will be placed over the left DLPFC and the contralateral area, as in the active stimulation condition. However, the current will be delivered only for the first 5 seconds, preventing the participants from detecting the placebo condition while ensuring that no neuromodulation occurs in the underlying brain areas. Patients will undergo a tDCS session on days 1, 2, 3, 4, 5, 12, 19, and 26 of the study. Each session will last 20

Primary outcome measures

• Beck Depression Inventory-II (BDI-II) [Time frame: 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)]
• Montgomery-Åsberg Depression Rating Scale (MADRS) [Time frame: 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)]
• Visual Analog Scale (VAS) [Time frame: 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 outcome measures (11)

• State-Trait Anxiety Inventory (STAI) [Time frame: 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)]
• Apathy Evaluation Scale (AES) [Time frame: 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)]
• Parkinson's Disease Questionnaire-8 (PDQ-8) [Time frame: 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)]
• Pittsburgh Sleep Quality Index (PSQI) [Time frame: 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)]
• EEG Peak Frequency in the Beta Band (Hz) [Time frame: 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)]
• Blink Reflex Area (mV·ms) [Time frame: 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)]
• Blink Reflex Duration (ms) [Time frame: 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)]
• Blink Reflex Latency (ms) [Time frame: 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)]
• Startle Saccadic Reflex Area (mV·ms) [Time frame: 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)]
• Startle Saccadic Reflex Duration (ms) [Time frame: 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)]
• Startle Saccadic Reflex Latency (ms) [Time frame: 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)]

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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Italy · 1 center

• Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico — Milan

Identifiers

NCT: NCT06885138 · 4531 · tDCS&PD

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗