Home-based Transcranial Stimulation in the Treatment of Patients With Refractory Chronic Pain

Not Applicable

• Conditions: Chronic Pain

• Registration Number: NCT05099406
• Lead Sponsor: University of Santiago de Compostela

Brief Summary

Refractory chronic pain represents a serious and limiting health condition which does not respond to standard pharmacological therapy. Thus, it emerges the necessity of new techniques to treat these group of diseases, such as the transcranial electrical stimulation (tES). This procedure induces a low-intensity electrical current through the scalp to modify the excitability of brain cells, thus facilitating changes in neural networks which may be dysfunctional in some chronic pain patients.

The main objective of this research is to test the efficacy of two tES techniques, differentiated by applying direct or alternant electrical current, to reduce the pain intensity and to increase pain thresholds of these patients. Besides, intervention is implemented at home for patients themselves thanks to a portable and convenient stimulator device, after one training session provided by technicians. Researches can supervise the compliance of the treatment remotely, as the stimulator has a permanent connection with their computers. A home-based approach means a more comfortable and accessible treatment alternative for patients, since they do not have to attend to clinics everyday to receive the stimulation; the advantages become even more relevant in the pandemic context, since the risk of being infected is radically minimized.

Despite the main purpose is to test the efficacy of tES to improve the pain suffered by patients, many other areas are considered as secondary end points for being intrinsically linked or affected by the disease, such as the interference in daily tasks provoked by pain, mood disorders (depression/anxiety), fatigue, life quality, physical functioning and sleep quality; these last two variables are measured with actigraph wristwatches, apart from specific questionnaires. Lastly, endogenous modulatory pain mechanisms are examined through sensory tests, namely Conditioned Pain Modulation and Temporal Summation of pain.

Detailed Description

This work aims to provide answers to the refractory chronic pain challenge. Pain is defined as refractory when multiple evidence-based biomedical therapies have failed to reach treatment goals that may include adequate pain reduction and/or improvement in daily functioning, even after appropriately assessing and addressing those psychosocial factors that could influence pain outcomes. In this sense, on the one hand, the study focus on detecting central biomarkers of pain modulation and processing which will contribute to improving knowledge of the mechanisms of pain chronification and the diagnosis procedure. On the other hand, given the low efficacy of pharmacological or non-pharmacological therapies for the patients studied, the efficacy of new therapeutic alternatives (tES) is explored. In short, the project will allow the transfer of knowledge to clinical practice in several aspects, such as diagnosis or treatment.

Therefore, the research aims to test the role of defective central pain modulation/processing as explanatory mechanisms for chronic pain. A second main objective is to test the efficacy of transcranial electric stimulation (tES) to modify dysfunction of central mechanism of pain, and to improve symptoms and quality of life in refractory chronic pain patients.

To achieve this, the investigators will select valid and reliable instruments to assess pain and comorbid symptoms in chronic pain patients and the most sensitive outcome measures to assess tES treatment efficacy. Sensory testing paradigms, namely Conditioned Pain Modulation, Temporal Summation of Second Pain and pain-related evoked potentials using electroencephalographic recordings, will act as biomarkers which are proposed to correlate with the severity of the chronic pain disease or some of their symptoms, and also as predictors of the treatment outcome.

Total sample includes 120 patients with refractory pharmaco-resistant pain, attended at the Pain Units of two Public Galician Hospitals (36 male, 84 female).

The study is expected to contribute to detection and preventive measures of future pain, and diagnosis of chronic pain disorders, improving prognosis and development of feasible patient-centered interventions, providing new directions for future research on pain.

Study Timeline

• Study First Submitted: 2021-08-30
• Status Verified: 2021-10
• Study First Submitted QC: 2021-10-18
• Last Update Submitted: 2021-10-18
• Study First Posted: 2021-10-29
• Last Update Posted: 2021-10-29
• Study Start: 2022-01-01
• Primary Completion: 2023-05-01
• Study Completion: 2023-05-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

• Suffering a chronic pain condition of non-cancer nature. Those patients who report chronic pain even after overcoming an oncological process are suitable to participate, but only if they have received the definitive medical discharge and have been free from radiotherapy/chemotherapy for at least twelve months.
• Adult subjects (18-65 years old).
• Subjects able to provide informed consent to participate in the study and to self-report pain.
• Existing chronic pain which reaches an intensity of at least 4 on a 0-10 Numeric Rating Scale (NRS) on average over the past 3 months prior to enrolment.
• Pain intensity of at least 5 on a 0-10 NRS over the week prior to enrolment.
• Diagnosis of pharmaco-resistance to analgesic drugs across the WHO ladder.
• Pharmacological regimen have kept stable for at least two months previous to the enrolment, and it must not suffer modifications during the whole research period.

Exclusion Criteria

• Chronic pain derived from current cancer disease.
• Pregnant women or women in fertile age not having efficacious contraception during the whole period of the study.
• History of alcohol or drug abuse within the past 6 months as self-reported.
• Suffering from unstable medical conditions (e.g., uncontrolled diabetes, uncompensated cardiac issues, heart failure or chronic obstructive pulmonary disease).
• Intracranial ferromagnetic devices or implanted stimulator (basal ganglia stimulator, vagus nerve stimulation).
• Antecedents of, or active epilepsy.
• History of neurosurgery, psychiatric diseases other than anxiety or depression, traumatic brain injury with loss of consciousness, and/or cortical lesions.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Self-reported pain intensity	Pre-treatment measure is the average of pain intensity of fifteen days previous to treatment; whereas the post-treatment measure is the average of fifteen days after treatment have finished	Participants must evaluate the intensity of their pain using an online version of a Numerical Rating Scale of eleven points (0-10), so that the higher the score is, the worse the pain is.

Secondary Outcome Measures

Name	Time	Method
Global severity of chronic pain syndrome	Participants will complete MPI one or two days before the treatment onset, and one or two days after treatment ending.	Composed index about the gravity of the chronic pain condition, taking into account several parameters as social and professional limitations due to pain, frequency and intensity of pain crisis, among others. The severity of chronic pain syndrome is assessed with global and subscales scores of Multidimensional Pain Inventory (MPI). Higher scores are indicative of worse health condition.
Pressure pain threshold	Pressure pain thresholds will be assessed in face-to-face laboratory sessions, which would take place one or two days before the treatment onset and one or two days after treatment ending.	Pressure pain threshold is defined as the minimum force necessary to induce pain in the participant, measured using a manual algometer and operationalized in kPa.
Heat pain threshold	Heat pain thresholds will be assessed in face-to-face laboratory sessions, which would take place one or two days before the treatment onset and one or two days after treatment ending.	Heat pain threshold is stablished as the temperature, measured in degrees Celsius, at which participant starts to feel pain, using a thermal stimulator.
Interference in daily living caused by pain	Pain interference will be assessed in face-to-face laboratory sessions, which would take place one or two days before the treatment onset and one or two days after treatment ending.	Subscales of Multidimensional Pain Inventory (MPI) are used to evaluate whether patients usually leave undone or are not capable to do some daily activities and tasks due to the pain they suffer from. The test consists of a numerical rating scale of seven points (0-6), so that the higher the score is, the more pronounced is the interference due to pain.
Life quality	Life quality will be assessed one or two days before the treatment onset and one or two days after treatment ending.	General health status considering physical, emotional and social functionality, as well as physical and mental health. Life quality is measured using the Short Form-36 Health Survey (SF-36). Higher scores are indicative of better health condition.
Physical condition and functioning	Estimations about daily energy expenditure, based on sedentary and activity bouts are recorded with wristband actigraphs which participants must wear during the whole research period.	Involvement and time-spent in physical activities or exercises.
Sleep quality and disturbances	Wristband actigraph are given to patients fifteen days before the treatment onset, so sleep habits are monitorized since that moment, until fifteen days after treatment have finished	Sleep habits of participants, as total sleep time. This sleep parameter is measured using the data recorded for wristband actigraphs which participants must wear during the whole research period.
Pain unpleasantness	Pre-treatment measure is the average of pain unpleasantness obtained from fifteen daily assessments previous to treatment; whereas the post-treatment measure is the average obtained from the fifteen days after treatment have finished	Affective component of pain, which refers to the discomfort or distress which pain provokes in patients. Participants must evaluate the discomfort produced by pain using an online version of a Numerical Rating Scale of eleven points (0-10), so that the higher the score is, the more stressful the pain is.
Mood disorders	Participants will complete HADS at two time-points, this is, one or two days before the treatment onset and one or two days after treatment ending.	Depressive and anxiety symptomatology which can concur with chronic pain conditions. Mood alterations are measured using the Hospital Anxiety and Depression Scale (HADS). Higher scores are indicative of a worse mood state.
Anxiety	Pre-treatment measure is the average of anxiety levels obtained from fifteen daily assessments previous to treatment; whereas the post-treatment measure is the average obtained from the fifteen days after treatment have finished	General anxiety level are evaluated with a daily frequency using an online version of a Numerical Rating Scale of eleven points (0-10), so that the higher the score is, the higher the anxiety level is.
Fatigue	Fatigue is registered with a daily frequency since the fifteen days before the treatment onset, until fifteen days after treatment ending. Participants will complete the MFIS at two time-points, this is, one or two days before and after treatment.	Tiredness which may result in difficulties to perform physical or psychological tasks. Fatigue and its consequences are measured using the Modified Impact Fatigue Scale (MFIS). Numerical Rating Scales of eleven points (0-10) are also used to assess daily fatigue levels. In both cases, higher scores are indicative of a greater fatigue.
Caregiver burden	Caregivers are invited to a face-to-face interview with researchers one or two days before the treatment onset and one or two days after treatment ending.	Stress levels which are subjected the caregivers of chronic pain patients are evaluated through the Zarit Burden Interview (ZBI) to assess if tES treatment means a reduction in burden derived from caring tasks. Higher scores are indicative of a more pronounced caregiver burden.
Global satisfaction with treatment and self-perceived improvement	Participants will evaluate their satisfaction with treatment a few days after it had finished.	Patients are asked to rate their satisfaction with the tES treatment and whether they believe it has helped to improve their health status, using an ad-hoc designed questionnaire.

Trial Locations

Locations (1)

University of Santiago de Compostela; 🇪🇸 Santiago De Compostela, A Coruña, Spain