Periodic Reporting for period 1 - PAINLESS (Pain relief in palliative care of cancer using home-based neuromodulation and predictive biomarkers)
Periodo di rendicontazione: 2022-06-01 al 2023-11-30
Pain is one of the most debilitating symptoms, with a negative impact on the well-being of patients with cancer. In addition, pain management in palliative care has mainly relied on applying the WHO “analgesic ladder”, despite 20% of patients showing a low response to pharmacological interventions and adverse side effects. The limitations of the pharmacological management of pain highlight the need to apply and use innovative technology-based products/solutions to implement optimal palliative care practices. Although cancer pain is very frequent, its neurophysiological mechanisms are poorly understood. In PAINLESS, we will improve the understanding of the neurophysiological mechanisms of cancer pain through the study of biomarkers of central pain modulation and will adapt and test an alternative treatment based on neuromodulation. The goal is to reduce the dependency of pain management on opioids (at least 50%) and to improve the well-being of cancer patients in need of palliative, end-of-life, or survivorship care and their formal and informal caregivers. To gradually reduce the dependence on analgesics, the patients' medication diary will be implemented within the neuromodulation procedure. To achieve these objectives, we design two inter-related studies.
The first study attempts to improve the knowledge on cancer pain mechanisms by using central modulation biomarkers to characterize and profile the patients. We will assess Temporal Summation of Pain (TSP), Conditioned Pain Modulation (CPM), Heat Pain Threshold (HPT), Cold Detection Threshold (CDT), Cold Pain Threshold (CPT), Offset Analgesia (OA), Resting state EEG, Resting state EEG during cold pain and Contact-Heat Evoked Potentials (CHEPs). As those biomarkers have been identified as good predictors of response to pharmacological treatment, our proposal to stratify patients will a) improve prognosis and assist in the decision for efficient therapeutic strategies, avoiding patients having to go through the long process of trial and error until the most appropriate treatment is found; b) allow to select the best therapy based on central pain biomarkers, and make a patient-centred intervention for chronic pain a reality. It has already been recognised that identifying pain biomarkers is a promising tool to individualise pain medicine and improve clinical management of pain.
For the second study, we firstly will adapt a home-based, remotely-supervised, non-invasive transcranial electric stimulation (tES) treatment system for cancer patients with chronic pain, an easy-to-use wearable wireless system suitable for use at home and in non-clinical environments. We will develop a customised cloud platform for remote management and supervision of home-based treatment, with smartphone-based registration of symptoms, side effects and protocols for error-free home-based treatment that could be easily integrated into the regular care of cancer pain. Then, we will perform a pilot study to achieve the main objective of the PAINLESS project, i.e. to test the efficacy of a home-based neuromodulation treatment to manage cancer pain. We will conduct a double-blind, randomised pilot study comparing the effects of active tDCS (transcranial direct current stimulation), active tACS (transcranial alternating current stimulation) and sham tES on several primary and secondary outcomes.
The first study attempts to improve the knowledge on cancer pain mechanisms by using central modulation biomarkers to characterize and profile the patients. We will assess Temporal Summation of Pain (TSP), Conditioned Pain Modulation (CPM), Heat Pain Threshold (HPT), Cold Detection Threshold (CDT), Cold Pain Threshold (CPT), Offset Analgesia (OA), Resting state EEG, Resting state EEG during cold pain and Contact-Heat Evoked Potentials (CHEPs). As those biomarkers have been identified as good predictors of response to pharmacological treatment, our proposal to stratify patients will a) improve prognosis and assist in the decision for efficient therapeutic strategies, avoiding patients having to go through the long process of trial and error until the most appropriate treatment is found; b) allow to select the best therapy based on central pain biomarkers, and make a patient-centred intervention for chronic pain a reality. It has already been recognised that identifying pain biomarkers is a promising tool to individualise pain medicine and improve clinical management of pain.
For the second study, we firstly will adapt a home-based, remotely-supervised, non-invasive transcranial electric stimulation (tES) treatment system for cancer patients with chronic pain, an easy-to-use wearable wireless system suitable for use at home and in non-clinical environments. We will develop a customised cloud platform for remote management and supervision of home-based treatment, with smartphone-based registration of symptoms, side effects and protocols for error-free home-based treatment that could be easily integrated into the regular care of cancer pain. Then, we will perform a pilot study to achieve the main objective of the PAINLESS project, i.e. to test the efficacy of a home-based neuromodulation treatment to manage cancer pain. We will conduct a double-blind, randomised pilot study comparing the effects of active tDCS (transcranial direct current stimulation), active tACS (transcranial alternating current stimulation) and sham tES on several primary and secondary outcomes.
Activities performed:
- Selection of a set of instruments to assess the main symptoms and comorbidities of chronic pain and relevant clinical information concerning the cancer disease, age, lifestyle, and sex of patients.
- Translate and adapt the instruments to the languages used by the Consortium members and make them accessible in the portal of the project, to be completed online by the participants or sent by smartphone.
- Technical adaptation of a thermal continuous stimulator (TCS) and development of a cold plate for CPM developed by the company.
- Preparation of a TCS equipment operational manual to be used for the rest of the groups.
- Selection of the assessment tools and stimulation parameters/equipment for QST and definition of the parameters for EEG recordings.
- Technical adaptation of EEG system to be used for bedside assessment and definition of parameters for measuring and analysing nociceptive contact heat evoked potentials (CHEPS) and for resting state EEG recording and analysis.
- Training tutorial with detailed explanations of the evaluation sessions of the other research members of the Consortium to ensure standardized application of the protocol and common procedures for EEG/EPs analysis.
- Sample recruitment, data collection and analysis of 450 patients with a recent diagnosis of cancer, performing selected questionnaires, QST and EEG. - ongoing
- Statistical analyses and implementation of AI algorithm to predict cancer pain occurrence. - ongoing
- Selection of a set of instruments to assess the main symptoms and comorbidities of chronic pain and relevant clinical information concerning the cancer disease, age, lifestyle, and sex of patients.
- Translate and adapt the instruments to the languages used by the Consortium members and make them accessible in the portal of the project, to be completed online by the participants or sent by smartphone.
- Technical adaptation of a thermal continuous stimulator (TCS) and development of a cold plate for CPM developed by the company.
- Preparation of a TCS equipment operational manual to be used for the rest of the groups.
- Selection of the assessment tools and stimulation parameters/equipment for QST and definition of the parameters for EEG recordings.
- Technical adaptation of EEG system to be used for bedside assessment and definition of parameters for measuring and analysing nociceptive contact heat evoked potentials (CHEPS) and for resting state EEG recording and analysis.
- Training tutorial with detailed explanations of the evaluation sessions of the other research members of the Consortium to ensure standardized application of the protocol and common procedures for EEG/EPs analysis.
- Sample recruitment, data collection and analysis of 450 patients with a recent diagnosis of cancer, performing selected questionnaires, QST and EEG. - ongoing
- Statistical analyses and implementation of AI algorithm to predict cancer pain occurrence. - ongoing
The major impact so far of the project is the implementation of a routine methodology to evaluate pain sensitivity as aimed by the project. Furthermore, the creation of awareness of the objective existence of biomarkers to evaluate cancer pain sensitivity has been an achievement.