Skip to main content
OpenTrials
Completed

NCT Number: NCT04651699

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Hospital Beata Maria Ana

Madrid, 28007, Spain

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Active Transcranial Direct Current Stimulation

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

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.

Primary outcomes

  1. Change in King´s Parkinson´s Disease Pain Scale score

    Time frame: From Baseline at 2 weeks

    Parkinson´s Disease specific scale that evaluates the localization, frequency, and intensity of pain. It has 14 items distributed in 7 domains: 1. Musculoskeletal Pain; 2. Chronic Pain; 3. Fluctuation-related Pain; 4. Nocturnal Pain; 5. Oro-facial Pain; 6. Discoloration, Oedema/Swelling Pain; 7. Radicular Pain. Each item is scored by severity (0, none to 3, very severe) multiplied by frequency (0, never to 4, all the time) resulting in a subscore of 0 to 12, the sum of which gives the total score with a theoretical range from 0 to 168, with higher scores indicating more severity and frequency of pain.

  2. Change in King´s Parkinson´s Disease Pain Scale score

    Time frame: From Baseline at 1 month

    Parkinson´s Disease specific scale that evaluates the localization, frequency, and intensity of pain. It has 14 items distributed in 7 domains: 1. Musculoskeletal Pain; 2. Chronic Pain; 3. Fluctuation-related Pain; 4. Nocturnal Pain; 5. Oro-facial Pain; 6. Discoloration, Oedema/Swelling Pain; 7. Radicular Pain. Each item is scored by severity (0, none to 3, very severe) multiplied by frequency (0, never to 4, all the time) resulting in a subscore of 0 to 12, the sum of which gives the total score with a theoretical range from 0 to 168, with higher scores indicating more severity and frequency of pain.

  3. Change in Brief Pain Inventory score

    Time frame: From Baseline at 2 weeks

    It contains 15 items, including 2 multi-item scales to measure the intensity of pain and its impact on the function and welfare of patients. It also presents open questions to assess the localization of pain and the treatment used for its management, just as its effectiveness. Scores oscillate from 0 to 110, with higher scores indicating more pain and more impact on function and welfare of patients.

  4. Change in Brief Pain Inventory score

    Time frame: From Baseline at 1 month

    It contains 15 items, including 2 multi-item scales to measure the intensity of pain and its impact on the function and welfare of patients. It also presents open questions to assess the localization of pain and the treatment used for its management, just as its effectiveness. Scores oscillate from 0 to 110, with higher scores indicating more pain and more impact on function and welfare of patients.

  5. Change in Conditioned Pain Modulation

    Time frame: From Baseline at 2 weeks

    Assesses the descending pain modulatory system. The Pain Pressure Threshold will be assessed in the middle of the distal phalanx of the thumb with ta handheld algometer, corresponding to the first test stimulus. Afterward, the patient will immerse the contrary hand up to the wrist into stirred ice-cold water (0-4º) maintaining it for 3 minutes, corresponding to the conditioning stimulus. If the pain is unbearable before the 3 minutes, the patient will be able to remove his/her hand. Immediately after removing the hand, a second Pain Pressure Threshold measure will be performed in the same place as the first one, corresponding to the second test stimulus. After 1-minute rest, a third Pain Pressure Threshold will be measured to assess the Conditioned Pain Modulation residual functioning.

  6. Change in Conditioned Pain Modulation

    Time frame: From Baseline at 1 month

    Assesses the descending pain modulatory system. The Pain Pressure Threshold will be assessed in the middle of the distal phalanx of the thumb with ta handheld algometer, corresponding to the first test stimulus. Afterward, the patient will immerse the contrary hand up to the wrist into stirred ice-cold water (0-4º) maintaining it for 3 minutes, corresponding to the conditioning stimulus. If the pain is unbearable before the 3 minutes, the patient will be able to remove his/her hand. Immediately after removing the hand, a second Pain Pressure Threshold measure will be performed in the same place as the first one, corresponding to the second test stimulus. After 1-minute rest, a third Pain Pressure Threshold will be measured to assess the Conditioned Pain Modulation residual functioning.

  7. Change in Temporal Summation

    Time frame: From Baseline at 2 weeks

    Represents excitatory modulation processes. It will be generated through the application of 10 pulses of the handheld pressure algometer over the middle of the distal phalanx of the thumb with the intensity of the Pain Pressure Threshold, previously calculated. In each pulse, pressure intensity will be increasing at a rate of 2 kg/s over the previously determined Pain Pressure Threshold intensity, leaving an interstimulus interval of one second according to the optimal method reported for inducing Temporal Summation with pressure pain. Before the first pressure pulse, subjects were taught to use a verbal numeric pain rating scale to rate the pain intensity of the first, fifth, and 10th pressure pulses. The verbal numeric pain rating scale ranged from 0 ("no pain") to 10 ("the worst possible pain").

  8. Change in Temporal Summation

    Time frame: From Baseline at 1 month

    Represents excitatory modulation processes. It will be generated through the application of 10 pulses of the handheld pressure algometer over the middle of the distal phalanx of the thumb with the intensity of the Pain Pressure Threshold, previously calculated. In each pulse, pressure intensity will be increasing at a rate of 2 kg/s over the previously determined Pain Pressure Threshold intensity, leaving an interstimulus interval of one second according to the optimal method reported for inducing Temporal Summation with pressure pain. Before the first pressure pulse, subjects were taught to use a verbal numeric pain rating scale to rate the pain intensity of the first, fifth, and 10th pressure pulses. The verbal numeric pain rating scale ranged from 0 ("no pain") to 10 ("the worst possible pain").

  9. Changes in Pain Pressure Threshold

    Time frame: From Baseline at 2 weeks

    Two Pain Pressure Thresholds will be measured by a handheld algometer, one over the most painful area (peripheric hyperalgesia) and the other one over the middle of the distal phalanx of the thumb (central hyperalgesia). The Pain Pressure Threshold will be applied with the algometer perpendicular to the skin increasing at a rate of 1 kg/s until the first sensation of pain. 3 measures with 30-seconds rest between them will be performed, taking the average as Pain Pressure Threshold.

  10. Changes in Pain Pressure Threshold

    Time frame: From Baseline at 1 month

    Two Pain Pressure Thresholds will be measured by a handheld algometer, one over the most painful area (peripheric hyperalgesia) and the other one over the middle of the distal phalanx of the thumb (central hyperalgesia). The Pain Pressure Threshold will be applied with the algometer perpendicular to the skin increasing at a rate of 1 kg/s until the first sensation of pain. 3 measures with 30-seconds rest between them will be performed, taking the average as Pain Pressure Threshold.

Secondary outcomes

  1. Beck Depression Inventory

    Time frame: Baseline

    Measures depressive symptoms. Scores range from 0 to 63 leading to 6 groups: 0-10, normal; 11-16, mild mood disturbance; 17-20, borderline clinical depression; 21-30, moderate depression; 31-40, severe depression; and over 40, extreme depression.

  2. Beck Depression Inventory

    Time frame: At 2 weeks from Baseline

    Measures depressive symptoms. Scores range from 0 to 63 leading to 6 groups: 0-10, normal; 11-16, mild mood disturbance; 17-20, borderline clinical depression; 21-30, moderate depression; 31-40, severe depression; and over 40, extreme depression.

  3. Beck Depression Inventory

    Time frame: At 1 month from Baseline

    Measures depressive symptoms. Scores range from 0 to 63 leading to 6 groups: 0-10, normal; 11-16, mild mood disturbance; 17-20, borderline clinical depression; 21-30, moderate depression; 31-40, severe depression; and over 40, extreme depression.

  4. State-Trait Anxiety Inventory

    Time frame: Baseline

    Measures anxious states and anxious traits. It has 20 items for assessing trait anxiety and 20 for state anxiety. All items are rated on a 4-point scale (e.g., from "Almost Never" to "Almost Always"). Higher scores indicate greater anxiety.

  5. State-Trait Anxiety Inventory

    Time frame: At 2 weeks from Baseline

    Measures anxious states and anxious traits. It has 20 items for assessing trait anxiety and 20 for state anxiety. All items are rated on a 4-point scale (e.g., from "Almost Never" to "Almost Always"). Higher scores indicate greater anxiety.

  6. State-Trait Anxiety Inventory

    Time frame: At 1 month from Baseline

    Measures anxious states and anxious traits. It has 20 items for assessing trait anxiety and 20 for state anxiety. All items are rated on a 4-point scale (e.g., from "Almost Never" to "Almost Always"). Higher scores indicate greater anxiety.

  7. Tampa Scale of Kinesiophobia

    Time frame: Baseline

    Measures fear of movement-related pain. Its scores range from 11-44 points with higher scores indicating greater fear of pain, movement, and injury.

  8. Tampa Scale of Kinesiophobia

    Time frame: At 2 weeks from Baseline

    Measures fear of movement-related pain. Its scores range from 11-44 points with higher scores indicating greater fear of pain, movement, and injury.

  9. Tampa Scale of Kinesiophobia

    Time frame: At 1 month from Baseline

    Measures fear of movement-related pain. Its scores range from 11-44 points with higher scores indicating greater fear of pain, movement, and injury.

  10. Pain Catastrophizing Scale

    Time frame: Baseline

    Measures catastrophizing thinking. Its total score range from 0-52, along with three subscale scores assessing rumination, magnification and helplessness, with higher scores indicating higher level of catastrophizing.

  11. Pain Catastrophizing Scale

    Time frame: At 2 weeks from Baseline

    Measures catastrophizing thinking. Its total score range from 0-52, along with three subscale scores assessing rumination, magnification and helplessness, with higher scores indicating higher level of catastrophizing.

  12. Pain Catastrophizing Scale

    Time frame: At 1 month from Baseline

    Measures catastrophizing thinking. Its total score range from 0-52, along with three subscale scores assessing rumination, magnification and helplessness, with higher scores indicating higher level of catastrophizing.

  13. Unified Parkinson´s Disease Rating Scale

    Time frame: Baseline

    Measures disability in Parkinson´s Disease patients. The scale itself has four components: Part I, Mentation, Behavior and Mood; Part II, Activities of Daily Living; Part III, Motor aspects; Part IV, Associated Complications. Scores range from 0 to 159 with higher scores indicating more severity.

  14. Unified Parkinson´s Disease Rating Scale

    Time frame: At 2 weeks from Baseline

    Measures disability in Parkinson´s Disease patients. The scale itself has four components: Part I, Mentation, Behavior and Mood; Part II, Activities of Daily Living; Part III, Motor aspects; Part IV, Associated Complications. Scores range from 0 to 159 with higher scores indicating more severity.

  15. Unified Parkinson´s Disease Rating Scale

    Time frame: At 1 month from Baseline

    Measures disability in Parkinson´s Disease patients. The scale itself has four components: Part I, Mentation, Behavior and Mood; Part II, Activities of Daily Living; Part III, Motor aspects; Part IV, Associated Complications. Scores range from 0 to 159 with higher scores indicating more severity.

  16. Reaction Times

    Time frame: Baseline

    Performed through 2 related subtasks. Finger Taping task, where the participants will be instructed to press the space bar on the keyboard as fast as possible and repeatedly with the index finger, to measure motor function. And Simple Reaction Time task, where participants will be instructed to press the left mouse button as fast as possible when the stimulus "+" appears in the center of the screen at a size of 2 cm x 2 cm, to measure simple perception and sustained alertness.

  17. Reaction Times

    Time frame: At 2 weeks from Baseline

    Performed through 2 related subtasks. Finger Taping task, where the participants will be instructed to press the space bar on the keyboard as fast as possible and repeatedly with the index finger, to measure motor function. And Simple Reaction Time task, where participants will be instructed to press the left mouse button as fast as possible when the stimulus "+" appears in the center of the screen at a size of 2 cm x 2 cm, to measure simple perception and sustained alertness.

  18. Reaction Times

    Time frame: At 1 month from Baseline

    Performed through 2 related subtasks. Finger Taping task, where the participants will be instructed to press the space bar on the keyboard as fast as possible and repeatedly with the index finger, to measure motor function. And Simple Reaction Time task, where participants will be instructed to press the left mouse button as fast as possible when the stimulus "+" appears in the center of the screen at a size of 2 cm x 2 cm, to measure simple perception and sustained alertness.

  19. Transcranial Magnetic Stimulation

    Time frame: Baseline

    Action Motor Threshold in millivolts

  20. Transcranial Magnetic Stimulation

    Time frame: At 2 weeks from Baseline

    Action Motor Threshold in millivolts

  21. Transcranial Magnetic Stimulation

    Time frame: At 1 month from Baseline

    Action Motor Threshold in millivolts

Sponsors and collaborators

Lead sponsor

Universidad Francisco de Vitoria

Other

Collaborators

  • Hospital Beata María Ana
  • Universidad Rey Juan Carlos

Registry information

Official study title

Non-Invasive Brain Stimulation Targeting Pain in Parkinson´s Disease Patients: A Randomized Controlled Trial

Important dates

Study start
2021
Primary completion
2022
Study completion
2023
First posted
Dec 3, 2020
Registry last updated
Jan 26, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.