Non-Invasive Brain Stimulation for the Treatment of Parkinson´s Disease-related Pain

NCT ID: NCT04651699

Last Updated: 2023-01-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-05-03
• Study Completion Date: 2023-01-23

Brief Summary

Pain is an under-reported but prevalent symptom in Parkinson´s Disease (PD), impacting patients' quality of life. Both pain and PD conditions cause cortical excitability reduction, but non-invasive brain stimulation is thought to be able to counteract it, resulting also effective in chronic pain conditions. The investigators in the present project aim to evaluate the efficacy of a novel brain stimulation protocol in the management of pain in PD patients during the ON state. The investigators hypothesize that active transcranial direct current stimulation (a-tDCS) over the Primary Motor Cortex (M1) can improve clinical pain and its central processing features.

Detailed Description

Parkinson´s Disease (PD) affects between 4.1 and 4.6 million people in the world. Diagnosis of PD is currently clinical and based on its motor manifestations (bradykinesia, rest tremor, and rigidity). However, non-motor symptoms such as pain, fatigue and neuropsychiatric manifestations are present in more than 70% of subjects. Pain affects about 85% of patients but is paradoxically under-reported and consequently under-treated in PD patients with a great impact on their quality of life. Levodopa, which is the election treatment in PD, has shown controversial results regarding pain sensitivity and has been shown ineffective for enhancing the endogenous pain modulation system. Furthermore, there is a lack of management protocols and nonpharmacologic treatments for pain in PD. Several syndromes are hypothesized to be involved in PD pain generation. Generally, PD patients suffer from alterations in peripheral transmission, sensitive-discriminative processing, pain perception, and pain interpretation in multiple levels, due to neurodegenerative changes in dopaminergic pathways and non-dopaminergic pain-related structures. Therefore, central mechanisms are proposed to be crucial for the development and establishment of pain in PD patients. Regarding pain processing features, PD patients have reduced pain thresholds, an augmented Temporal Summation (TS) after repetitive nociceptive stimulus, and the impairment of their Conditioned Pain Modulation (CPM) is correlated with greater severity and premature onset of the disease. Cortical excitability reduction is common in patients with pain. Therefore, diverse therapies are being developed to counteract this cortical excitability reduction and obtaining, consequently, effective pain relief. In consonance with these findings, in PD condition, especially in off state, there is also evidence of cortical excitability decrease but, to the best of the investigators´ knowledge, there are no studies targeting cortical excitability to treat pain in PD. Thus, the present study proposes non-invasive brain stimulation therapy for the treatment of PD-related pain. The non-invasive brain stimulation therapy will be transcranial direct current stimulation (tDCS) over the Primary Motor Cortex (M1). tDCS over M1 is capable of increase corticospinal excitability in both M1 and other pain processing-related areas such as the thalamus, Dorsolateral Prefrontal Cortex (DLPFC), cingulate cortex, and insula, also involved in PD pain processing. These increments of cortical excitability have been correlated with pain relief in chronic pain such as fibromyalgia, osteoarthritis, migraine, and spinal cord injury. It is also hypothesized that tDCS would be an effective strategy to treat central sensitivity-related pain, a process whose features are common with PD condition. Moreover, specifically in PD, tDCS over M1 has shown to increase cortical excitability, augmenting the Motor Evoked Potential (MEP) amplitude by 78.5%, correlating with motor improvements. The main aim of this study is to conduct an independent parallel randomized controlled trial based on tDCS targeting changes in 1. validated general and specific PD related pain scales and 2. psychophysical measurements of pain modulation mechanisms. The investigators´ main hypothesis is that active tDCS will be superior to its respective control placebo intervention.

Conditions

Parkinson Disease; Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Active Transcranial Direct Current Stimulation

Active Transcranial Direct Current Stimulation (a-tDCS) will be applied over the Primary Motor Cortex during 10 sessions of 20 minutes at 2 milli amps.

Group Type: EXPERIMENTAL

Active Transcranial Direct Current Stimulation

Intervention Type: DEVICE

The Starstim tDCS® stimulator will be used by an experienced physical therapist to transfer direct current by a saline-soak pair of surface sponge electrodes (35cm2). The anode electrode will be placed over C3 (EEG 10/20 system) and the cathode electrode over the contralateral supraorbital area (Fp2), in order to enhance the excitability of M1 (32). Regarding the stimulated hemisphere, contralateral M1 will be stimulated in patients with asymmetric pain and the dominant (contrary to the dominant hand determined by the Edinburgh Handedness Inventory) in patients with symmetric pain, due to the widespread changes induced by tDCS in other cortical areas, including contralateral M1. A constant current of 2 milli amps intensity (subthreshold intensity) will be applied for 20 min, with 30 seconds of ramp-up and 30 seconds of ramp-down.

Sham Transcranial Direct Current Stimulation

Sham Transcranial Direct Current (s-tDCS) will be applied over the Primary Motor Cortex during 10 sessions of 20 minutes.

Group Type: SHAM_COMPARATOR

Sham Transcranial Direct Current Stimulation

Intervention Type: DEVICE

The electrodes will be placed in the same positions as for M1 stimulation, but only applying ramping active current for 30 seconds in the beginning and at the end of the procedure for a reliable blinding.

Interventions

Active Transcranial Direct Current Stimulation

The Starstim tDCS® stimulator will be used by an experienced physical therapist to transfer direct current by a saline-soak pair of surface sponge electrodes (35cm2). The anode electrode will be placed over C3 (EEG 10/20 system) and the cathode electrode over the contralateral supraorbital area (Fp2), in order to enhance the excitability of M1 (32). Regarding the stimulated hemisphere, contralateral M1 will be stimulated in patients with asymmetric pain and the dominant (contrary to the dominant hand determined by the Edinburgh Handedness Inventory) in patients with symmetric pain, due to the widespread changes induced by tDCS in other cortical areas, including contralateral M1. A constant current of 2 milli amps intensity (subthreshold intensity) will be applied for 20 min, with 30 seconds of ramp-up and 30 seconds of ramp-down.

Intervention Type: DEVICE

Sham Transcranial Direct Current Stimulation

The electrodes will be placed in the same positions as for M1 stimulation, but only applying ramping active current for 30 seconds in the beginning and at the end of the procedure for a reliable blinding.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Neuroimaging study without previous pathologies.
• Score > 5 in transfers (bed to chair and back) item in Barthel Index.
• Score = or > 24 in Mini-Mental State Examination.
• Tolerability for the application of electrotherapy.
• Able to provide informed consent to participate in the study.

Exclusion Criteria

• Neurologic disease different from PD.
• Pain non-related to PD.
• Dermatologic problems, wounds, or ulcers in the electrode's application area.
• Presence of implants or metal pieces in the head.
• Presence of cardiac pacemaker, vagal, brain or transcutaneous stimulators, medication pumps, ventriculoperitoneal shunts or aneurysm clips.
• Significative difficulties in language.
• History of alcohol or drugs abuse.
• Non-controlled medical problems.
• Pregnancy.
• Epilepsy.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Universidad Rey Juan Carlos

OTHER

Sponsor Role: collaborator

Hospital Beata María Ana

OTHER

Sponsor Role: collaborator

Universidad Francisco de Vitoria

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Juan Pablo Romero Muñoz, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Universidad Francisco de Vitoria, Facultad de Ciencias Experimentales

Josué Fernandez Carnero, PT PhD

Role: PRINCIPAL_INVESTIGATOR

Universidad Rey Juan Carlos

Locations

Hospital Beata Maria Ana

Madrid, , Spain

Countries

Spain

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Other Identifiers

PainPD-tDCS

Identifier Type: -

Identifier Source: org_study_id