Clinical and Neurophysiological Effects of tDCS on Depression in Parkinson's Disease

NCT06885138 | Enrolling By Invitation

• 2 other identifiers: 4531tDCS&PD
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

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:
• 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.
• 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.
• 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.

Conditions

PARKINSON DISEASE (Disorder)

Keywords

Depression; Parkinson Disease; tDCS

Outcome Measures

Primary Outcomes (3)

• Beck Depression Inventory-II (BDI-II)

  The Beck Depression Inventory-II (BDI-II) is a 21-item, self-report rating inventory that measures characteristic attitudes and symptoms of depression. Each item is scored on a scale from 0 to 3, with total scores ranging from 0 to 63. Higher scores indicate more severe depressive symptoms.

  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)

  The Montgomery-Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire which mental health professionals use to measure the severity of depressive episodes in patients with mood disorders. Each item is rated from 0 to 6, leading to a total score range of 0 to 60. Higher scores indicate more severe depression.

  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)

  The Visual Analog Scale (VAS) for mood is a widely used tool to assess a person's emotional state. It consists of a straight line, usually 100 mm in length, with one end representing the most negative mood state (e.g., very sad, depressed) and the other end representing the most positive mood state (e.g., very happy, elated). The individual marks a point on the line that corresponds to their current mood, and the distance from the "negative" end to the mark is then measured in millimeters, providing a quantitative measure of the individual's emotional state. Scores range from 0 to 10, with higher scores indicating a more positive mood. This scale is easy to use and provides a subjective yet reliable way to track mood changes over time.

  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 (11)

• State-Trait Anxiety Inventory (STAI)

  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)

  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)

  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)

  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)

  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)

Study Arms (2)

Sham tDCS

SHAM COMPARATOR

Patients in this group will receive sham transcranial Direct Current Stimulation (tDCS)

Device: sham transcranial Direct Current Stimulation

Active tDCS

EXPERIMENTAL

Patients in this group will receive active transcranial Direct Current Stimulation (tDCS) (stimulation polarity: anodal).

Device: active transcranial Direct Current Stimulation

Interventions

active transcranial Direct Current Stimulation DEVICE

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.

Also known as: Neuromodulation

Active tDCS

sham transcranial Direct Current Stimulation DEVICE

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 minutes.

Also known as: Neuromodulation

Sham tDCS

Eligibility Criteria

• Age: 35 Years - 75 Years
• Gender Eligibility Details: All
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: lead

Study Sites (1)

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

MeSH Terms

Conditions

Parkinson Disease; Depression

Interventions

Transcutaneous Electric Nerve Stimulation

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Physical Therapy Modalities; Rehabilitation; Analgesia; Anesthesia and Analgesia

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: February 18, 2025
• First Posted: March 20, 2025
• Study Start: April 23, 2024
• Primary Completion: February 1, 2026
• Study Completion (Estimated): February 1, 2027
• Last Updated: March 20, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)