E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chemotherapy Induced Peripheral Neuropathy (CIPN) |
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E.1.1.1 | Medical condition in easily understood language |
Nerve damage due to the patient receiving chemotherapy which causes pain |
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E.1.1.2 | Therapeutic area | Body processes [G] - Bones and nerves physological processes [G11] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10040039 |
E.1.2 | Term | Sensory peripheral neuropathy |
E.1.2 | System Organ Class | 100000004852 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine whether 6 weeks of topical 3% menthol gel provides effective analgesia for neuropathic pain, using the Brief Pain Inventory Short Form to assess this outcome. |
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E.2.2 | Secondary objectives of the trial |
To determine whether 6 weeks of topical 3% menthol gel affects various sensory and quality of life functions at 6 weeks and again at 12 weeks (6 weeks after treatment).
To determine whether 6 weeks of topical 3% menthol gel shows changes in fMRI scan data at 6 weeks. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
(a) Patients have received any neurotoxic chemotherapy.
(b) Patients have experienced post treatment Chemotherapy Induced Peripheral Neuropathy (CIPN) pain for a minimum of 3 months after completing chemotherapy.
(c) Patients reporting a distressing or uncomfortable neuropathic symptom (such as pain or tingling) with an average score in the last 24 hours of ≥5 on a scale of 0-10 with 0 being none, according to the Numeric Rating Scale for pain.
(d) Aged 18 years or over at study entry.
(e) Patient’s Oncology team agrees to their taking part in the study.
(f) Patients are able to provide written informed consent to participation in the study after explanation of the study protocol.
(g) In the opinion of the investigator, the patient is able to complete the various assessments.
(h) Neuropathy must be confined to the distal extremities (distal to elbows and/or knees).
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E.4 | Principal exclusion criteria |
(a) Pre-existing or history of peripheral neuropathy due to any cause other than chemotherapy (diabetes, alcohol, toxin, hereditary, etc.).
(b) Patients with any contraindication to the use of topical therapy or menthol.
(c) Neurological conditions which may influence findings (such as Multiple Sclerosis or residual signs/symptoms from a previous stroke).
(d) Skin conditions which prevent assessment of the relevant areas affected by peripheral neuropathy.
(e) Suffering from significant psychiatric illness, which would hinder their completion of the study in the opinion of the investigator.
(f) General medical condition is unstable or rapidly deteriorating, such that they are unlikely to be able to contribute to the study.
(g) In the opinion of the Research Team or their usual medical team, would be unable to complete the study protocol for any other reason.
(h) Current treatment of ≤ 30 days duration with anticonvulsants, tricyclic antidepressants, MAO inhibitor, or other neuropathic pain medication agents such as carbamazepine, phenytoin, valproic acid, gabapentin/pregabalin, lamotrigine or amifostine. (If on the same dose of any of these medications for >31 days, patients will be asked to continue these for the duration of the study. Analgesic agents such as acetaminophen, nonsteroidal anti-inflammatory agents, or opioids, are allowed if on the same doses for >31 days).
(i) Application of topical lidocaine patch/gel or capsaicin cream or patch (to the limb extremities) currently or within the last 30 days (as this would interfere with application of the menthol gel and potentially study outcome).
(j) Patients with significant pain other than CIPN (ie pain worse than the CIPN).
(k) Patients with a pain that is likely to emerge during the scan because of position.
(l) Other medical conditions, which in the opinion of the treating physician/allied health professional would make this protocol unreasonably hazardous for the patient.
(m) Contraindication to MRI: e.g. aneurysm clips, pacemaker, other metal work in body, claustrophobia.
(n) Participants previously randomised into this study.
(o) Participants not prepared to stop using any other physical activity meter.
(p) Co-enrolment in any other pain treatment studies.
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E.5 End points |
E.5.1 | Primary end point(s) |
A clinically significant reduction in pain (at least a 30% decrease in total BPI SF score as relates to the index neuropathic pain) between baseline and 6 weeks.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
6 weeks after start of treatment. |
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E.5.2 | Secondary end point(s) |
Changes between baseline and 6 weeks in: o Combined sensory and motor scales for CIPN (CIPN-20) o Quality of life (EORTC QLQc30 Version 3) summary scores o BPI scores: Pain Severity (questions 3-6) Pain Interference (questions 9 A-G) Aggregate (sum of severity and interference scores) o Anxiety and depression (HADS) o Side effects o Psychophysical testing (QST) o Physical Activity data, daily averages of: Daily Step Count Light/Moderate Activity Sleep Amount Sleep Efficiency • Perceived effects of IMP: Length of time for IMP to take effect Length of time IMP remains effective • Withdrawal from study in the active drug group versus the placebo group • Serious adverse events in the active drug group versus the placebo group
Tertiary endpoints: To determine whether 6 weeks of topical 3% menthol gel shows changes in fMRI scan data and to assess changes in sensory and quality of life functions at 6 weeks after treatment.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Trial End will be on the day of the last assessment of the last subject undergoing the trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 20 |