Central pain processing and modulation biomarkers profile in chronic pain prediction in patients with cancer
| ISRCTN | ISRCTN14475880 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14475880 |
- Submission date
- 28/03/2023
- Registration date
- 21/07/2023
- Last edited
- 05/03/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Plain English summary of protocol
Background and study aims
Previous research on biomarkers of cancer pain has been focused on the study of blood samples and as a condition, chemotherapy-induced neuropathic pain. This study will extend the investigation of biomarkers (including biomarkers of central pain modulation) to the most common types of cancer pain (breast, lung, pancreas and colon cancer) and to the stage before the cancer treatment. Thus, in this study, the researchers will select a panel of biomarkers related to the central processing and modulation of pain, propose a bedside assessment protocol, and analyse their power to predict the appearance of pain. In addition, they will assess the most relevant clinical domains/outcomes (other illnesses, main symptoms, cancer characteristics, etc) and other moderator variables (age, sex, lifestyle). There are some previous positive results that support the use of quantitative sensory tests (QST) as predictors of chronic pain appearance or responsiveness to treatment. In some studies, dysfunctional conditioned pain modulation predicted future chronic pain development after various interventions and also analgesic effectiveness towards therapeutic interventions. Regarding cancer, QST data have also demonstrated that the presence of pre-existing sensory deficits before chemotherapy are a contributing factor to the onset of painful chemotherapy-induced peripheral neuropathy (CIPN). Moreover, it has been observed that that QST indices were predictors of response to therapy in cancer-induced bone pain. Nevertheless, no specific bedsite protocol assessment of central pain biomarkers nor specific tools for cancer pain prediction have been developed so far. Thus, the final goal of this study is to develop a prediction tool for cancer pain (including central pain biomarkers, clinical and sociodemographic variables) through artificial intelligence (AI) analysis.
Who can participate?
Patients aged 18 years and over who have had a recent diagnosis of cancer
What does the study involve?
Participants will complete an assessment that will include an initial interview and questionnaires/tests about their health condition. Also, there will be sensory testing and an electroencephalogram (EEG, a recording of brain activity). During the interview, the researchers will collect relevant sociodemographic data (e.g., sex, age, lifestyle) and clinical history (other illnesses, type of tumor, extension, time since diagnosis, evolution, previous chronic diseases, risk factors for cancer, antecedents of cancer). The researchers will ask the patients for authorization to access data from their clinical records.
What are the possible benefits and risks of participating?
There are no direct benefits from participating in this study except perhaps the individual satisfaction in contributing to research that helps to improve the application of new predictive biomarkers in clinical settings.
Where is the study run from?
IPO Porto (Portugal)
When is the study starting and how long is it expected to run for?
June 2022 to January 2027
Who is funding the study?
Horizon Europe Framework Programme
Who is the main contact?
1. Maria Teresa Carrillo, mteresa.carrillo@usc.es
2. Rui Medeiros, ruimedei@ipoporto.min-saude.pt
Contact information
Scientific
R António Bernardino de Almeida
Porto
4200-072
Portugal
 ORCID ID |
0000-0003-3010-8373 |
|---|---|
| Phone | +351 (0)225084000 |
| ruimedei@ipoporto.min-saude.pt |
Principal Investigator
Colexio De San Xerome Praza Do Obradoiro S/n
Santiago de Compostela
15782
Spain
| ORCID ID |
0000-0001-6940-2460 |
|---|---|
| Phone | +34 (0)881 813798 |
| mteresa.carrillo@usc.es |
Study information
| Study design | Multi-centre longitudinal cohort observational study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cohort study |
| Study setting(s) | Care home, Hospital |
| Study type | Quality of life |
| Participant information sheet | Not available in web format |
| Scientific title | Selection of a panel of biomarkers of central pain processing and modulation, and assessment of their validity to predict chronic pain in patients with cancer - WP1 |
| Study acronym | PAINLESS-PredictCANCERPAIN (WP1) |
| Study objectives | Poorer pain modulation mechanisms at pre-cancer treatment in the patients who will develop chronic pain at 6 and 12 months later. |
| Ethics approval(s) |
Approved 19/01/2023, Comissão de Ética para a Saúde - Instituto Português de Oncologia do Porto (R. Dr. António Bernardino de Almeida 865, Porto, 4200-072, Portugal; +351 (0)225 084 000; diripo@ipoporto.min-saude.pt), ref: CES.05/023 |
| Health condition(s) or problem(s) studied | Cancer |
| Intervention | After signing the informed consent, participants will complete an assessment protocol that will include an initial interview and questionnaires/tests about their health condition (in digital files). Also, the researchers will assess quantitative sensory testing (Temporal Summation of Pain [TSP], Conditioned Pain Modulation [CPM], Heat Pain Threshold [HPT], Cold Detection Threshold [CDT], Cold Pain Threshold [CPT], Offset Analgesia [OA], thermal stimulator [TCS], electroencephalography [EEG], contact heat evoked potentials [CHEPS]) using a TCS device and a cold plate, and EEG and CHEPs registry using an ambulatory EEG device. During the interview, they will collect relevant sociodemographic data to characterize the sample (e.g., sex, age, lifestyle) and data from the clinical history (comorbidities, type of tumor, extension, time since diagnosis, evolution, previous chronic diseases, risk factors for cancer, antecedents of cancer). In the informed consent the researchers will ask the patients for authorization to access data from their clinical records. Each assessment session will have an estimated duration of 2 hours and will take place at the hospitals at three timepoints: before the antineoplastic treatment, 6 months after Visit 1 (basal assessment) and 12 months after Visit 1 (basal assessment). The complete participation in the study will take around 6 hours. |
| Intervention type | Device |
| Pharmaceutical study type(s) | Not Applicable |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | - |
| Primary outcome measure | Measured before the antineoplastic treatment, 6 months after Visit 1 (basal assessment) and 12 months after Visit 1 (basal assessment): 1. Pain intensity and distress measured using an 11-point (0-10) numerical rating scale (NRS) measure of pain intensity (in the last week) and an NRS for distress (unpleasantness) caused by pain 2. Functional impact of pain and quality of life (QoL) measured using the Brief Pain Inventory (BPI), the Short Form 36 Health Survey (SF-36) and EQ- 5D-3L (EuroQol) 3. Functionality or performance status measured using the Eastern Cooperative Oncology Group (ECOG) scale 4. Sleep quality measured using the Pittsburgh Sleep Quality Index (PSQI) 5. Fatigue measured using the Modified Fatigue Impact Scale (MFIS) 6. Emotional functioning measured using the Brief Measure for Assessing General Anxiety Disorder (GAD7) and the Patient Health Questionnaire (PHQ-9) 7. Catastrophizing measured using the Pain Catastrophism Scale (PCS) |
| Secondary outcome measures | There are no secondary outcome measures |
| Overall study start date | 01/06/2022 |
| Completion date | 01/01/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 450 |
| Key inclusion criteria | Current inclusion criteria as of 05/03/2025: 1. Adult subjects ≥18 years old 2. Able to provide informed consent to participate in the study 3. Able to self-report pain 4. Recent diagnosis (less than 6 months) of cancer affecting the lung, breast, pancreas or colon (with metastases or not) 5. Not having started systemic cancer treatment 6. Have a life expectancy of at least 12 months 7. Ability to use the internet and WhatsApp or have a person (family member, caregiver) to help them Previous inclusion criteria: 1. Adult subjects ≥18 years old 2. Able to provide informed consent to participate in the study 3. Able to self-report pain 4. Recent diagnosis (less than 6 months) of cancer affecting the lung, breast, pancreas or colon (with metastases or not) 5. Not having started cancer treatment (all treatments are included) 6. Have a life expectancy of at least 12 months 7. Ability to use the internet and WhatsApp or have a person (family member, caregiver) to help them |
| Key exclusion criteria | 1. Pregnant women or women of fertile age not having efficacious contraception during the whole period of the study 2. Neurological and psychiatric disease (except anxiety and depression) 3. Unstable medical conditions (e.g., uncontrolled diabetes, uncompensated cardiac issues, heart failure or chronic obstructive pulmonary disease) 4. History of neurosurgery, traumatic brain injury with loss of consciousness, and/or cortical lesions 5. History of non-malignant chronic pain |
| Date of first enrolment | 01/04/2023 |
| Date of final enrolment | 31/03/2026 |
Locations
Countries of recruitment
- Denmark
- Portugal
- Romania
- Spain
Study participating centres
Porto
4200-072
Portugal
Santiago de Compostela
15703
Spain
Santiago De Compostela
15706
Spain
Vigo
36312
Spain
Aalborg
9220
Denmark
Bucharest
022328
Romania
Sponsor information
Government
R António Bernardino de Almeida
Porto
4200-072
Portugal
| Phone | +351 (0)225084000 |
|---|---|
| centro.investigacao@ipoporto.min-saude.pt | |
| Website | https://ipoporto.pt/ |
"ROR" |
https://ror.org/027ras364 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- Horizon Europe, Horizon Europe Programme, Framework Programme, Horizon Europe, EU Framework Programme, Horizon
Results and Publications
| Intention to publish date | 01/02/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | In order to share knowledge with other experts and professionals, the findings of the current study will be reported in papers that will be published in open-access, high-impact, peer-reviewed scientific publications (at least one per relevant work package) in the areas of palliative care, oncology, pain and neuroscience. Blogs, congress abstracts and presentations (at least two at every EAPC congress and specialized international conferences during the project) and webinars will be also planned. Moreover, contact with relevant stakeholders and policymakers is also planned. |
| IPD sharing plan | Concerning data protection, the researchers will comply with the directives of the General Data Protection Regulation (GDPR), approved by the European Commission on April 27, 2016 (UE 2016/679). They will be advised by the Data Protection Officer of each of the involved institutions. They assure the confidentiality of all the data generated from the project. All the information will be codified, and none of the digital files will contain personal identification data. The datasets generated during and/or analysed during the current study are/will be available upon request from Rui Medeiros (ruimedei@ipoporto.min-saude.pt) and Maria Teresa Carillho de La Pena (mteresa.carrillo@usc.es). The type of data that will be shared: biomarkers output and clinical outcomes. Dates of availability: at the end of the project. Consent from participants was required and obtained at the recruitment stage. All data will undergo an anonymization procedure. All procedures were approved by the ethical authorities and Data Protection Officer (DPO). |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | 08/06/2024 | 10/06/2024 | Yes | No |
Editorial Notes
05/03/2025: The following changes were made to the study record:
1. The inclusion criteria were updated.
2. The recruitment end date was changed from 31/03/2025 to 31/03/2026.
3. The overall study end date was changed from 01/10/2025 to 01/01/2027.
10/06/2024: Publication reference added.
14/12/2023: Internal review.
16/05/2023: Study's existence confirmed by the ethics committee of the Portuguese Oncology Institute of Porto.
