Clinical trial NCT04651699: Non-Invasive Brain Stimulation for the Treatment of Parkinson´s Disease-related Pain
Official title: Non-Invasive Brain Stimulation Targeting Pain in Parkinson´s Disease Patients: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Parkinson Disease
Pain
Keywords: Parkinson Disease
Pain
tDCS
Lead sponsor: Universidad Francisco de Vitoria
Sponsor class: OTHER
Collaborators: name: Universidad Rey Juan Carlos
name: Hospital Beata María Ana
First posted: 2020-12-03
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study will be a triple-blinded experimental longitudinal prospective randomized controlled trial with a parallel design. The randomization will be realized through the "GraphPad" software by an independent investigator. All the participants who fulfill the inclusion criteria and have none of the exclusion ones will be randomly allocated into two groups: active-tDCS (a-tDCS) or sham-tDCS (s-tDCS). Allocation concealment will be ensured by the inclusion of the assigned group in closed opaque envelopes that will be opened at the time of the intervention.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change in King´s Parkinson´s Disease Pain Scale score
timeFrame: From Baseline at 2 weeks
measure: Change in King´s Parkinson´s Disease Pain Scale score
timeFrame: From Baseline at 1 month
measure: Change in Brief Pain Inventory score
timeFrame: From Baseline at 2 weeks
measure: Change in Brief Pain Inventory score
timeFrame: From Baseline at 1 month
measure: Change in Conditioned Pain Modulation
timeFrame: From Baseline at 2 weeks
measure: Change in Conditioned Pain Modulation
timeFrame: From Baseline at 1 month
measure: Change in Temporal Summation
timeFrame: From Baseline at 2 weeks
measure: Change in Temporal Summation
timeFrame: From Baseline at 1 month
measure: Changes in Pain Pressure Threshold
timeFrame: From Baseline at 2 weeks
measure: Changes in Pain Pressure Threshold
timeFrame: From Baseline at 1 month
Secondary outcomes:
measure: Beck Depression Inventory
timeFrame: Baseline
measure: Beck Depression Inventory
timeFrame: At 2 weeks from Baseline
measure: Beck Depression Inventory
timeFrame: At 1 month from Baseline
measure: State-Trait Anxiety Inventory
timeFrame: Baseline
measure: State-Trait Anxiety Inventory
timeFrame: At 2 weeks from Baseline
measure: State-Trait Anxiety Inventory
timeFrame: At 1 month from Baseline
measure: Tampa Scale of Kinesiophobia
timeFrame: Baseline
measure: Tampa Scale of Kinesiophobia
timeFrame: At 2 weeks from Baseline
measure: Tampa Scale of Kinesiophobia
timeFrame: At 1 month from Baseline
measure: Pain Catastrophizing Scale
timeFrame: Baseline
measure: Pain Catastrophizing Scale
timeFrame: At 2 weeks from Baseline
measure: Pain Catastrophizing Scale
timeFrame: At 1 month from Baseline
measure: Unified Parkinson´s Disease Rating Scale
timeFrame: Baseline
measure: Unified Parkinson´s Disease Rating Scale
timeFrame: At 2 weeks from Baseline
measure: Unified Parkinson´s Disease Rating Scale
timeFrame: At 1 month from Baseline
measure: Reaction Times
timeFrame: Baseline
measure: Reaction Times
timeFrame: At 2 weeks from Baseline
measure: Reaction Times
timeFrame: At 1 month from Baseline
measure: Transcranial Magnetic Stimulation
timeFrame: Baseline
measure: Transcranial Magnetic Stimulation
timeFrame: At 2 weeks from Baseline
measure: Transcranial Magnetic Stimulation
timeFrame: At 1 month from Baseline
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Hospital Beata Maria Ana
Study officials:
affiliation: Universidad Francisco de Vitoria, Facultad de Ciencias Experimentales
name: Juan Pablo Romero Muñoz, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universidad Rey Juan Carlos
name: Josué Fernandez Carnero, PT PhD
role: PRINCIPAL_INVESTIGATOR
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