Brain and Pain (BaP): Understanding the Central Mechanisms of Pain to Improve Management of Patients With Refractory Chronic Pain
试验速览
- 阶段
- 不适用
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Self-reported pain intensity
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Portable devices for applying the transcranial electrical stimulation are equipped with a software which allows a double-blinded procedure. The same computer program is in charge of randomly allocating patients to one of the three treatment groups. Thus, nor the researchers neither the participants will know what kind of stimulation is receiving each of them.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Transcranial direct current stimulation (tDCS)
Fifteen stimulation sessions applied with a daily frequency during an uninterrupted period of time which comprises just over two weeks. Current intensity of 2mA is applied during 20 minutes at the left M1, with anodal electrode placed in C3 and cathodal in FP2, following the International 10-20 EEG System. Ramp-up and ramp-down comprises 15 seconds at the beginning and end of the stimulation period.
干预措施: Transcranial electrical stimulation (Device)
Transcranial alternant current stimulation (tACS)
Fifteen stimulation sessions applied with a daily frequency during an uninterrupted period of time which comprises just over two weeks. Two electrodes will be placed at F3 and F4 and connected together for 10-Hz tACS (or the frequency which shows best sensitivity or specificity), and one electrode at Pz will be the return electrode. This setting is used to stimulate the somatosensory cortical region. Stimulation will last for 20 minutes, with a ramp-up and ramp-down of 15 seconds at the beginning and end of the session.
干预措施: Transcranial electrical stimulation (Device)
Sham stimulation
The electrode montage will be either the tDCS (for half of the participants) or the tACS montage (for the other half), and we will just apply the current at the ramps terms, but no current in the interval between the ramps which practically comprises the whole session. As for the two other group, fifteen sham stimulation sessions will be daily scheduled in a non-interrupted period of two weeks.
干预措施: Transcranial electrical stimulation (Device)
结局指标
主要结局
Self-reported pain intensity
时间窗: 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.
次要结局
- 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.)
- 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.)
- 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.)
- 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.)
- Life quality(Life quality will be assessed one or two days before the treatment onset and one or two days after treatment ending.)
- 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.)
- 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)
- 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)
- 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.)
- 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)
- 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.)
- 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.)
- Global satisfaction with treatment and self-perceived improvement(Participants will evaluate their satisfaction with treatment a few days after it had finished.)
- Sleep quality and disturbances(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.)
研究者
María Teresa Carrillo de la Peña
Titular university professor (PhD)
University of Santiago de Compostela