Clinical trial NCT05099406: Home-based Transcranial Stimulation in the Treatment of Patients With Refractory Chronic Pain
Official title: Brain and Pain (BaP): Understanding the Central Mechanisms of Pain to Improve Management of Patients With Refractory Chronic Pain
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Chronic Pain
Keywords: Transcranial electrical stimulation
Fibromyalgia
Arthritis
Arthrosis
Low back pain
Migraine headaches
Anxiety disorders
Depression
Chronic fatigue
Sleep disorders
Pain assessment
EEG
Lead sponsor: University of Santiago de Compostela
Sponsor class: OTHER
Collaborators: name: Ministry of Science and Innovation, Spain
name: Health Research Institute of Santiago de Compostela - IDIS (Recruitment support)
name: Fundación Biomédica Galicia Sur (Recruitment support)
First posted: 2021-10-29
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomly assigned to one of three treatment groups (40% active tDCS; 40% Active tACS; 20% Sham). Patients receiving sham stimulation will act as the control group.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Self-reported pain intensity
timeFrame: 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
Secondary outcomes:
measure: Global severity of chronic pain syndrome
timeFrame: Participants will complete MPI one or two days before the treatment onset, and one or two days after treatment ending.
measure: Pressure pain threshold
timeFrame: 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.
measure: Heat pain threshold
timeFrame: 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.
measure: Interference in daily living caused by pain
timeFrame: 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.
measure: Life quality
timeFrame: Life quality will be assessed one or two days before the treatment onset and one or two days after treatment ending.
measure: Physical condition and functioning
timeFrame: 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.
measure: Sleep quality and disturbances
timeFrame: Participants will complete PQSI at two time-points, this is, one or two days before the treatment onset and one or two days after treatment ending.
measure: Sleep quality and disturbances
timeFrame: 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
measure: Pain unpleasantness
timeFrame: 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
measure: Mood disorders
timeFrame: 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.
measure: Anxiety
timeFrame: 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
measure: Fatigue
timeFrame: 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.
measure: Caregiver burden
timeFrame: 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.
measure: Global satisfaction with treatment and self-perceived improvement
timeFrame: Participants will evaluate their satisfaction with treatment a few days after it had finished.
Other outcomes:
measure: Endogenous pain inhibition response
timeFrame: CPM procedure will be performed at two time-points, this is, one or two days before and after treatment, in order to assess if tES treatment is capable of restoring any dysfunction in this inhibitory pain network.
measure: Endogenous pain facilitation response
timeFrame: TSSP procedure will be performed at two time-points, this is, one or two days before and after treatment, in order to assess if tES treatment is capable of restoring any dysfunction in this facilitatory pain network.
measure: Electrical brain activity over diverse conditions
timeFrame: EEG will be registered at two time-points, this is, one or two days before and one or two days after treatment.
Locations:
city: Santiago De Compostela
country: Spain
facility: University of Santiago de Compostela
state: A Coruña
Study officials:
affiliation: University of Santiago de Compostela
name: María Teresa Carrillo de la Peña
role: PRINCIPAL_INVESTIGATOR
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