Chemotherapy induced peripheral neuropathy Nervous System Diseases
Conditions
Interventions
A clinical efficacy and mechanistic phase 2 RCT, of MRX1 versus matched placebo oral solution, using a randomised, double-blind, placebo-controlled, cross-over design. Participants will be randomised
Sponsors
University of Edinburgh
Eligibility
Sex/Gender
All
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. 18 years or over 2. At least 3 months post neurotoxic chemotherapy 3. Stable CIPN over at least 6 weeks 4. EORTC CIPN20 sensory scale > 10 5. 0-10 VAS (Visual Analogue Scale) PAIN = 3 6. Willing and able to give written consent 7. Willing not to take additional cannabinoids during the trial period 8. Willing to use effective contraception throughout the trial (A woman is considered of childbearing potential (WOCBP), i.e., fertile, following menarche and until becoming post-menopausal unless permanently sterile. See below for accepted effective contraception1. 9. Willing to continue effective contraception for 30 days after completion of trial for woman participants and for 90 days for male participants 10. No contraindications to MRI scan 1Methods considered to be effective contraceptives: - Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal) - Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable) - Intrauterine device (IUD) - Intrauterine hormone-releasing system (IUS) - Bilateral tubal occlusion - Vasectomised partner (provided that partner is the sole sexual partner of the WOCBP trial participant and that the vasectomised partner has received medical assessment of the surgical success) - Sexual abstinence, defined as refraining from heterosexual intercourse during the entire trial period and for 90 days post study completion. The reliability of sexual abstinence will be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not an acceptable method of contraception.
Exclusion criteria
Exclusion criteria: 1. Patients who have had any changes to analgesia in last 30 days 2. Patients who have had any intervention which may result in a change to CIPN during the course of the study *2 3. Patients currently taking any of the following medication; opioids, erythromycin, clarithromycin, fluconazole, itraconazole, sulfamethoxazole, clopidogrel, rifampicin, warfarin, selected antiepileptic agents (including phenytoin, carbamazepine, sodium valproate) clobazam, stiripentol, Everolimus *3 4. Patients currently taking any antidepressants and anticonvulsants if used as adjuvant analgesics 5. Routine use of cannabis products for medicinal or recreational purposes (at any time in the last 4 weeks) or of any illicit drug precludes inclusion in the study (CBD at Baseline) *4 6. Patients with severe pain due to CIPN on VAS;>8/10 7. Female patients who are not post-menopausal and not using highly effective contraception (as detailed at end of this section) 8. Male patients who are not using highly effective contraception with female partner (as detailed at the end of this section) 9. Patients who are pregnant or breastfeeding 10. Chronic alcohol use 11. Any liver disease with abnormal bilirubin, AST or ALT: History of severe liver disease (Alanine transaminase (ALT) and/or aspartate aminotransferase (AST) more than 3-times the upper limit of normal (ULN)) and bilirubin greater than 2 times the ULN OR moderate to severe hepatic impairment (Child–Pugh class B or C). 12. Current or recent (=12 months) substance use disorder or misuse of prescription medicines; positive drugs of abuse (DoA) screen when performed at investigator’s discretion. 13. Patients with hypersensitivity to any of constituents of IMP in the IB 14. Any hospital admission for mental ill health in last 5 years 15. Suicidal thoughts or severe depression within the past year 16. Any live vaccines within 14 days before study entry *2 Any treatment, oncological or non-oncological, which could change CIPN during the course of the study (including changes to hormone treatment in the 30 days prior to recruitment, patients who start neurotoxic chemotherapy during the study, patients who start any drug which can cause CIPN during the study). These are the most likely scenarios in our patient group which we are therefore giving as examples but this is not an exhaustive list. *3 All concomitant medication will be reviewed as part of the screening process. Relevant Cannabidiol–Psychoactive Drug Interactions, as listed in Appendix 1, will be considered. *4 Urine samples will be collected at baseline and week 8 (pre-dose) and analysed via a dipstick at time of collection. We can detect any THC taken in the previous 35-40 days with the dipstick which means in practical terms we will capture any illicit THC use. This is to measure any cannabis/cannabinoid use out with the IMP. If the test results are positive for THC the participant will be withdrawn.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Sensory peripheral neuropathy is measured using the EORTC QLQ-CIPN20 sensory scale at weeks 5 and 12 2. Resting-state functional connectivity of the anterior cingulate cortex is measured using rsfMRI at baseline and week 5 | — |
Secondary
| Measure | Time frame |
|---|---|
| Clinical: 1. Adverse events and side effects are measured using participant self-report and clinical records at weeks 5 and 12 2. Chemotherapy-induced peripheral neuropathy is measured using total EORTC CIPN 20 scores and EORTC QLQc30 scores at week 5 and 12 3. CIPN pain severity is measured using the Brief Pain Inventory short form (BPI sf) at weeks 5 and 12 4. Mood is measured using Generalised Anxiety Disorder-7 questionnaire (GAD7) and (Patient Health Questionnaire-9) PHQ9 total scores at week 5 and 12 5. Perceived cognitive function is measured using the FACT-Cog Version 3 total score at weeks 5 and 12 6. Sleep quality is measured using the Pittsburgh Sleep Quality Index at weeks 5 and 12 7. Health-related quality of life is measured using total EORTC QLQ-C30 scores at weeks 5 and 12 8. Somatosensory function is measured using quantitative sensory testing (QST) at weeks 5 and 12 9. Patient Global Impression of Change (PGIC) is measured using standardised questions at weeks 5 and 12 Health economic: 10. Health status is measured using the EQ-5D-5L at weeks 5, 8 and 12 11. Health care utilisation is measured using participant self-report and clinical records at weeks 5, 8 and 12 12. Cost-effectiveness is measured using modelled cost per QALY at weeks 5, 8 and 12 Mechanistic: 13. Resting-state functional connectivity and white matter microstructural integrity are measured using rsfMRI and diffusion MRI at week 5 14. Brain metabolite concentrations are measured using magnetic resonance spectroscopy at week 5 15. Endocannabinoid levels are measured using blood samples at baseline, weeks 5, 8 and 12 16. Inflammatory markers are measured using blood samples at weeks 5 and 12 Exploratory: 17. Period-dependent fluctuations in clinical outcomes including chemotherapy-induced peripheral neuropathy, quality of life, depression, anxiety and pain are measured using EORTC QLQ-CIPN20, EORTC QLQ-C30, PHQ-9, GAD-7 and BPI-SF at baseline, weeks 5, 8 and 12 18. Te | — |
Countries
United Kingdom
Contacts
Public ContactEmma Ward
Outcome results
None listed