Study investigating the impact, risk and mechanisms of neuropathic pain (nerve pain) associated with chemotherapy. Partnership for Assessment and Investigation of Neuropathic Pain (PAINSTORM)
| ISRCTN | ISRCTN13477304 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13477304 |
| IRAS number | 303039 |
| Secondary identifying numbers | 2-016-22, IRAS 303039, CPMS 53404 |
- Submission date
- 27/10/2022
- Registration date
- 15/11/2022
- Last edited
- 17/01/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nervous System Diseases
Plain English summary of protocol
Background and study aims
Nerve or ‘neuropathic’ pain can occur when the nerves are damaged in some way. Unfortunately, many of the commonly used and effective chemotherapies for cancer treatment can damage nerves. People may develop Chemotherapy Induced Peripheral Neuropathy (CIPN) with pain and numbness, particularly in the hands and feet, during or after treatment.
CIPN can be so severe that the dose of chemotherapy needs to be reduced, or even stopped, during treatment. There are no effective preventive treatments, and limited treatment options available if CIPN does develop. We do not understand why some people get neuropathic pain from chemotherapy whilst others do not, nor why it gets better in some people but
not in others. Research that we have done has found that sometimes factors such as a person’s lifestyle, other diseases they have, past experiences they’ve had and family history (genetics), can make someone more likely to develop neuropathic pain. We want to understand what things make someone more or less likely to develop CIPN, and how it changes over time. This will then help us develop ways to reduce the risk of developing CIPN, as well as hopefully preventing or treating it.
Who can participate?
Patients 18 years or older with a planned course of potentially neurotoxic chemotherapy for the treatment of cancer.
What does the study involve?
If you decide to take part in the study, you will be asked to attend study visits before starting chemotherapy, half-way through your chemotherapy and at the end of your chemotherapy.
At the first study visit, you will be asked to complete a consent form to confirm that you want to take part in the study. You will also be asked about your health and any medication you take. The following will also be recorded:
• Height and weight.
• Quantitative Sensory Testing (QST) – to examine nerve function. This includes checking how you feel different sensations such as temperature changes, light touch, and pin prick.
• Questionnaires – will be completed covering aspects of health, pain and quality of life. You will also be asked to complete questionnaires at home in between study visits, before each cycle of chemotherapy. Completed questionnaires can be sent in by email or completed online or sent by post.
The following activities are optional:
• Blood test
• Activity monitor – an activity monitor should be worn for 7 days to record steps per day and time spent sitting, standing and lying down.
• Brain MRI scan –100 participants will have a Magnetic Resonance Imaging (MRI) scan of their brain. The MRI will record any changes in nerves before and after chemotherapy.
Second and third visits
Activities:
• Quantitative Sensory Testing (QST) – as described for the first visit above
• Questionnaires
• Blood sample
• Activity monitor
• Brain MRI – on the third visit only.
After participants have finished their chemotherapy, they will be contacted again 3, 6, 9 and 12 months later to check their health and medication and complete a questionnaire. This follow-up contact will be by phone, online and/or by post.
What are the possible benefits and risks of participating?
Benefits:
The study might not bring benefit to participants personally, but the aim is to improve the treatment of people getting chemotherapy and to help to develop new ways to prevent or treat CIPN. Participants will be monitored closely for CIPN throughout their chemotherapy, with regular detailed assessments by an experienced research team. As participants are being monitored closely for CIPN, if they develop CIPN it might be picked it up more quickly than usual.
Risks:
It may be tiring for participants to have regular assessments throughout their chemotherapy.
Quantitative Sensory Testing (QST) involves checking how well participants can feel skin temperature, touch and pressure changes. These tests may cause mild discomfort to the skin or be slightly painful.
Wearing an activity monitor can sometimes cause mild skin irritation.
Where is the study run from?
University of Dundee (UK)
When is the study starting and how long is it expected to run for?
July 2021 to June 2025
Who is funding the study?
1. UK Research and Innovation
2. Versus Arthritis (UK)
3. Eli Lilly and Company (USA)
Who is the main contact?
Prof. Lesley Colvin, l.a.colvin@dundee.ac.uk
Contact information
Principal Investigator
Division of Population Health and Genomics
University of Dundee
Mackenzie Building
Ninewells Hospital
Dundee
DD1 9SY
United Kingdom
 ORCID ID |
0000-0002-1563-8600 |
|---|---|
| Phone | +44 1382381880 |
| l.a.colvin@dundee.ac.uk |
Study information
| Study design | Observational study of a longitudinal prospective cohort |
|---|---|
| Primary study design | Observational |
| Secondary study design | Longitudinal study |
| Study setting(s) | Hospital |
| Study type | Quality of life |
| Participant information sheet | See study outputs table |
| Scientific title | PAINSTORM: Partnership for Assessment and Investigation of NeuP: Studies Tracking Outcomes, Risks and Mechanisms |
| Study acronym | PAINSTORM Dundee CIPN study |
| Study objectives | An individual's risk of developing acute or chronic CIPN can be predicted by specific psychosocial, genetic and clinical risk factors. |
| Ethics approval(s) | Approved 05/09/2022, South Central - Hampshire A Research Ethics Committee (Temple Quay House, 2 The Square, Temple Quay, Bristol, BS1 6PN, UK; +44 2071048033/53; hampshirea.rec@hra.nhs.uk), ref: 22/SC/0233 |
| Health condition(s) or problem(s) studied | Chemotherapy Induced Peripheral Neuropathy (CIPN) |
| Intervention | The ultimate aim of the PAINSTORM consortium is to reach a new understanding of NeuP, by combining molecular, physiological and psychological approaches to describe its development and progression. An inter-disciplinary approach will be used to determine the interaction of these different factors (with ‘biological’ and ‘psychosocial’ factors given equal weight) and develop innovative technologies and person-centred outcome measures to identify these pathophysiological processes in patients. PAINSTORM Dundee CIPIN Study will contribute to this, by generating a new, deeply phenotyped cohort of people undergoing potentially neurotoxic chemotherapy. 200 patients receiving potentially neurotoxic chemotherapy will be invited to take part. Participants will be seen pre-, mid- and after their chemotherapy where a full medical, concomitant medication and demographic history will be recorded. Nerve function will be examined using Quantitative Sensory Testing, checking sensations such as temperature changes, light touch and pinprick. Participants will complete questionnaires covering their health, lifestyle, pain (characterisation, intensity and location) and quality of life including psychological and psychosocial aspects, these will also be completed before each cycle of chemotherapy. Optional activities will include blood tests for biomarker and genetic analysis and MRI will be offered to 100 participants to identify brain structural and functional changes associated with development of CIPN. |
| Intervention type | Other |
| Primary outcome measure | 1. Development (or persistence) of painless or painful CIPN measured: 1.1. Using change in chemotherapy/dose reduction due to neurotoxicity measured using EORTC-CIPN20 questionnaire at baseline, mid and end of chemotherapy 3, 6, 9 and 12 months after completion of chemotherapy. 1.2. By pain location using a list of body sites / Body map measured at baseline, mid and end of chemotherapy 3, 6, 9 and 12 months after completion of chemotherapy. 1.3. Using development (or persistence) of painless or painful CIPN measured by Total Neuropathy Score clinical (TNSc) questionnaire at baseline, mid and end of chemotherapy. 2. Pain severity change in Chronic Pain Grade and Brief Pain Inventory (BPI) Numeric Rating Scale (average in last 24 hours) at baseline mid and end of chemotherapy at 3, 6, 9 and 12 months after completion of chemotherapy. |
| Secondary outcome measures | 1. Lifestyle factors affecting CIPN measured using: 1.1. Eastern Cooperative Oncology Group (ECOG) Performance Status Scale, any changes to planned oncological treatment, Step count (ActivPALTM accelerometer), Patterns of daily living (time spent sitting, standing, stepping and lying) using ActivPALTM accelerometer measured at baseline, mid and end of chemotherapy 1.2. Past medical History/ co-morbidities, Family History, Details of cancer type and stage, Oncological treatment including planned chemo protocol (and any changes to this with reasons, Duration of CIPN, Smoking questionnaire, Alcohol questionnaire, Illicit drugs measured at baseline. 1.3. Physical function, measured using Saltin-Grimby Physical Activity Level Scale, and concomitant medication and at Baseline, mid and end of chemotherapy at 3, 6, 9 and 12 months after completion of chemotherapy. 2. Demographic factors affecting CIPN: Age, Sex, Scottish Index of Multiple Deprivation (SIMD), Weight, Height, Years in full-time education, Working status, Household income measured at baseline 3. Clinical factors affecting CIPN: Blood/ serum biomarkers measured at baseline, mid and end of chemotherapy. 4. Type and quality of pain affecting CIPN measured using Douleur Neuropathique en 4 (DN4) and NeuP Symptom Inventory (12 items) at baseline, mid and end of chemotherapy at 3, 6, 9 and 12 months after completion of chemotherapy. 5. Quality of lif affecting CIPN measured using EQ-5D-5L21, Brief Pain Inventory (BPI) Pain interference and Core MD Anderson Symptom Inventory (MDASI) questionnaires at baseline, mid and end of chemotherapy at 3, 6, 9 and 12 months after completion of chemotherapy. 6. Psychological Health factors affecting CIPN measured using • Patient-Reported Outcomes Measurement Information System (PROMIS): Depression; Anxiety; Sleep; Support Trauma, Pain Catastrophizing Scale, Inventory of Depressive Symptomatology (IDS-SR), The 7-item State Optimism Measure (SOM-7) and Ten Item Personality Inventory (TIPI) questionnaires at baseline, mid and end of chemotherapy at 3, 6, 9 and 12 months after completion of chemotherapy. |
| Overall study start date | 01/07/2021 |
| Completion date | 30/06/2025 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 150 |
| Key inclusion criteria | 1. 18 years or older 2. Planned course of potentially neurotoxic chemotherapy for the treatment of cancer. This includes the following: 2.1. Platinum drugs 2.2. Taxanes 2.3. Vinca alkaloids 2.4. Epothilones 2.5. Proteasome inhibitors 2.6. Thalidomide 2.7. Vedotin-based drugs 2.8. Checkpoint inhibitors |
| Key exclusion criteria | 1. Incapacity to give consent or to complete the study questionnaires due to insufficient language command or mental deficiencies, in the opinion of the investigator. 2. Functional impairment - ECOG Performance Status Scale great than or equal to 3 at baseline. 3. Concurrent clinically defined severe physical or psychiatric disorders that would preclude accurate phenotyping. 4. Moderate to severe pain from other causes that may confound assessment or reporting of pain if unable to differentiate from CIPN. 5. Patients who are in the opinion of the investigator, or treating oncology team, unsuitable for participation in the study. |
| Date of first enrolment | 01/12/2022 |
| Date of final enrolment | 30/06/2025 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
Study participating centres
Dundee
DD1 9SY
United Kingdom
Bristol Haematology & Oncology Centre
Horfield Road
Bristol
BS2 8ED
United Kingdom
Sponsor information
University/education
TASC
Level 3 Residency block
Ninewells Hospital, Dundee
Dundee
DD1 9SY
Scotland
United Kingdom
| Phone | +44 1382383297 |
|---|---|
| TASCgovernance@dundee.ac.uk | |
| Website | https://www.dundee.ac.uk/tasc/ |
"ROR" |
https://ror.org/03h2bxq36 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- UKRI
- Location
- United Kingdom
Private sector organisation / Other non-profit organizations
- Location
- United Kingdom
Government organisation / For-profit companies (industry)
- Alternative name(s)
- Lilly, Eli Lilly & Company, Eli Lilly & Co., Eli Lilly And Co
- Location
- United States of America
Results and Publications
| Intention to publish date | 01/01/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | There will be a clear PAINSTORM strategy for reporting and dissemination of scientific output, overseen by a dissemination committee. Patient partners will be active members of the dissemination committee. Patient partners will lead the identification of ways of disseminating the results and review outputs aimed at patients and public. Results will be written up in high impact open access scientific papers and presented at scientific conferences internationally. A PAINSTORM website will be created, with public access, and papers will be shared there. Where results potentially affect patient care, e.g. through the identification of stratified approaches to risk management, these will be shared with stakeholders such as patient groups, national regulatory and professional bodies, health professionals and the general public, with a view of maximising overall impact. A Final Report will be prepared for the funding body and for the Ethics Committee. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be available on request from Prof Lesley Colvin, l.a.colvin@dundee.ac.uk |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 1.0 | 25/05/2022 | 15/11/2022 | No | No |
| HRA research summary | 28/06/2023 | No | No |
Additional files
Editorial Notes
17/01/2025: The following changes were made to the study record:
1. The target number of participants was changed from 200 to 150.
2. The recruitment end date was changed from 31/12/2024 to 30/06/2025.
3. England was added to the countries of recruitment.
4. University Hospitals Bristol NHS Foundation Trust was added to the study participating centres.
25/01/2024: The following changes were made to the study record:
1. The recruitment end date was changed from 31/12/2023 to 31/12/2024.
2. The intention to publish date was changed from 01/01/2026 to 01/01/2027.
3. Study website added.
02/12/2022: Internal review.
15/11/2022: Trial's existence confirmed by South Central - Hampshire A Research Ethics Committee.
