Menthol In Neuropathy Trial (MINT)

A Phase II RCT of Topical Menthol Gel Versus Placebo in the Treatment of Chemotherapy Induced Peripheral Neuropathic Pain

Patients will be recruited who have peripheral neuropathy due to chemotherapy. They will be given a blinded treatment of gel containing either menthol (3%) or placebo to be applied for 6 weeks, twice a day. Assessments of pain, neuropathic symptoms and impact on quality of life will be done at baseline, 6 weeks and 12 weeks. Functional magnetic resonance imaging (fMRI) scans will be done at baseline and 6 weeks. Physical activity data will also be collected to be analysed in conjunction with pain assessments.

Study Overview

• Status: Completed
• Conditions: Chemotherapy-induced Peripheral Neuropathy
• Intervention / Treatment: Drug: MINT study IMP

Detailed Description

Modern cancer treatments, while more effective at prolonging life, are associated with some long lasting effects, especially nerve pain. This occurs in up to 90% of patients and 50% of patients still experience nerve pain a year after treatment. Not only is this distressing in itself but the investigators now understand that this treatment-related pain is exacerbating other pains, making cancer pain more difficult to control. The problem with managing nerve pain caused by treatment is that there is no predictable and effective treatment.

Our team has discovered that menthol cream or gel applied to the skin in the area of nerve pain can be effective. This trial seeks to provide better evidence of using this simple, cheap, non-toxic treatment. Participants will be given either menthol gel to the affected area or a placebo gel which smells, looks like and has the same texture as menthol but has no active drug. The gel will be applied twice a day for 6 weeks.

Participants will initially be assessed for pain and its impact on function, mood and quality of life and, if possible, will also have an fMRI scan immediately before starting menthol treatment and after 6 weeks of treatment. They will also have some assessments a further 6 weeks after treatment finishes. As part of impact on function assessment, participants will be asked to wear a physical activity monitor for a few days prior to each of the three main assessment points.

Our group has used special scans of the brain called fMRI to help identify if a treatment has real potential for patients. Sometimes, in early studies of a new treatment, patients can believe that the treatment has a real effect, but in fact it is a placebo effect. FMRI scans in this study will help to identify if menthol gel is having a true pain relieving effect, by comparing the patient's reports of pain with their scan findings. This will be very helpful in aiding the decision of how the research team conduct any future larger clinical trial.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Edinburgh, United Kingdom, EH4 2XU
    • Western General Hospital
  • Edinburgh, United Kingdom, EH4 2XR
    • Western General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients have received any neurotoxic chemotherapy.
2. Patients have experienced post treatment Chemotherapy Induced Peripheral Neuropathy (CIPN) pain for a minimum of 3 months after completing chemotherapy.
3. 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.
4. Aged 18 years or over at study entry.
5. Patient's Oncology team agrees to their taking part in the study.
6. Patients are able to provide written informed consent to participation in the study after explanation of the study protocol.
7. In the opinion of the investigator, the patient is able to complete the various assessments.
8. Neuropathy must be confined to the distal extremities (distal to elbows and/or knees).

Exclusion Criteria:

1. Pre-existing or history of peripheral neuropathy due to any cause other than chemotherapy (diabetes, alcohol, toxin, hereditary, etc.).
2. Patients with any contraindication to the use of topical therapy or menthol.
3. Neurological conditions which may influence findings (such as Multiple Sclerosis or residual signs/symptoms from a previous stroke).
4. Skin conditions which prevent assessment of the relevant areas affected by peripheral neuropathy.
5. Suffering from significant psychiatric illness, which would hinder their completion of the study in the opinion of the investigator.
6. General medical condition is unstable or rapidly deteriorating, such that they are unlikely to be able to contribute to the study.
7. In the opinion of the Research Team or their usual medical team, would be unable to complete the study protocol for any other reason.
8. Current treatment of ≤ 30 days duration with topical lidocaine patch/gel or 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).
9. Application of 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).
10. Patients with significant pain other than CIPN (ie pain worse than the CIPN).
11. Other medical conditions, which in the opinion of the treating physician/allied health professional would make this protocol unreasonably hazardous for the patient.
12. Participants previously randomised into this study.
13. Participants not prepared to stop using any other physical activity meter.
14. Co-enrolment in any other pain treatment studies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Menthol; Menthol gel to be applied twice a day for 6 weeks - toes to knees, fingertips to elbows, top and base of spine.	Drug: MINT study IMP; Application of gel for 6 weeks.
Placebo Comparator: Placebo; Placebo gel to be applied twice a day for 6 weeks - toes to knees, fingertips to elbows, top and base of spine.	Drug: MINT study IMP; Application of gel for 6 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction in CIPN symptoms	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.	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment effect on Chemotherapy Induced Peripheral Neuropathy	Changes in EORTC QLQ (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires) CIPN-20 (severity of 20 symptoms rated on 4 point scale from Not at all to Very much)	6 weeks
Treatment effect on quality of life functions	Changes in EORTC QLC-c30 scores (30 symptoms on same scale as CIPN)	6 weeks
Treatment effect on pain scores	Changes in Brief Pain Inventory - Short Form scores (13 symptoms rated from 0 None to 10 Worst)	6 weeks
Treatment effect on anxiety and depression	Changes in Hospital Anxiety and Depression Scale (HADS) scores	6 weeks (14 symptoms rated from 0 to 3 in severity)
Treatment effect on pain catastrophisation	Changes in Pain Catastrophising Scale (PCS) scores	6 weeks (13 questions rated from 0-4 in severity)
Treatment effect on side effects	Changes in side effects (Yes/No to any SEs, description of SE to be given)	6 weeks
Treatment effect on physical activity	Changes in Actigraph data (measures of step counts, amount of moderate/vigorous activity and sleep times/efficiency)	6 weeks
Perceived effects of IMP	Changes in perceived effects questions (How long participant thinks treatment takes to take effect and how long it lasts for)	6 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Functional Magnetic Imaging data	Changes in FMRI data pre and post treatment	6 weeks
Post treatment changes in CIPN	Changes in CIPN-20 scores (see secondary outcomes above for details of all questionnaire measures)	12 weeks (from baseline)
Post treatment changes in quality of life measures	Changes in QLQ-c30	12 weeks (from baseline)
Post treatment changes in pain scores	Changes in BPI-SF	12 weeks (from baseline)
Post treatment changes in anxiety and depression	Changes in HADS scores	12 weeks (from baseline)
Post treatment changes in pain catastrophising	Changes in PCS	12 weeks (from baseline)
Post treatment changes in side effects	Changes in Side effects	12 weeks (from baseline)
Post treatment changes in physical activity	Changes in Actigraph data	12 weeks (from baseline)
Changes in sensory measures	Changes in QST data	6 weeks and 12 weeks (from baseline)

Collaborators and Investigators

• Sponsor: University of Edinburgh
• Collaborators: NHS Lothian

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2019
• Primary Completion (Actual): March 24, 2022
• Study Completion (Actual): March 24, 2022

Study Registration Dates

• First Submitted: November 8, 2019
• First Submitted That Met QC Criteria: February 17, 2020
• First Posted (Actual): February 19, 2020

Study Record Updates

• Last Update Posted (Actual): September 14, 2022
• Last Update Submitted That Met QC Criteria: September 13, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Neuropathic pain; Chemotherapy; Peripheral neuropathy; CIPN
• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases
• Other Study ID Numbers: MINT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Anyone interested in secondary analysis of the data should contact the Chief Investigator in the first instance.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No