Topical Herbal Medicine for Chemotherapy-Induced Peripheral Neuropathy

Phase 2Active Not RecruitingNCT07693387

Taiwan Municipal An-Nan Hospital-China Medical University40 enrolled

Overview

The goal of this clinical trial is to learn if menthol works to relieve chronic neuropathic pain and chemotherapy-induced peripheral neuropathy (CIPN). The primary objectives are to evaluate the safety and clinical efficacy of menthol-containing gloves and foot-covers, specifically whether they can improve patient-reported hypoesthesia (numbness). Secondary objectives include assessing the sustained effects on pain, dysesthesia (abnormal sensations), allodynia (touch-induced pain), and overall quality of life. Additionally, this study will include an exploratory lab analysis using blood samples to investigate potential biological markers (small extracellular vesicles and microRNA) associated with treatment responses. Participants will be asked to: Wear menthol-containing gloves and foot-covers (or shams) daily for 5 minutes per session over a 14-day period. Attend clinic visits on Days 1, 14, 21, and 28 for evaluations and tests.

Our laboratory previously discovered a unique and simple-to-apply neuroprotective method involving topical menthol treatment. In an animal model, this approach demonstrated prominent anti-inflammatory effects and improved behavioral outcomes (published in the Journal of Neuroinflammation, 2022). Based on these findings, we hypothesize that topical menthol can alleviate chemotherapy-induced peripheral neuropathy (CIPN).To test this hypothesis, our team conducted a preliminary open-label clinical study (IRB: TMANH112-REC025) evaluating menthol-based gloves and foot-covers. The pilot results revealed that the 8% menthol concentration significantly improved tactile sensation sensitivity via von Frey monofilament testing. Notably, after a 14-day intervention, the therapeutic effects appeared to persist for up to 21 days.While the small sample size in the pilot stage limited the statistical power to detect significant differences in subjective symptoms like numbness (NRS) or overall quality of life, the trending improvements in physical tactile sensation warrant a rigorous validation. Therefore, this expanded, randomized, double-blind, placebo-controlled trial is scientifically designed to provide adequate statistical power to confirm the sustained clinical efficacy and safety of 8% topical menthol treatment, while exploring underlying biological mechanisms through plasma-derived small extracellular vesicle biomarker analysis in CIPN patients.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Eligibility

Sex: ALLMin age: 20 YearsMax age: 100 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 1\. All adult cancer patients (Age≧20-year-old) who received chemotherapy regimens, including adjuvant and neoadjuvant therapy. * 2\. Stage I-IV cancer patients. * 3\. Who received chemotherapy regimens, including Taxanes (paclitaxel or docetaxel), platinum (cisplatin, oxaliplatin, carboplatin). * 4\. Who have received two cycle or have completed the neurotoxic chemotherapy regimen(24). * 5\. Baseline von Frey Monofilament test (Target force at hand) ≧ 0.07gms. * 6\. Baseline von Frey Monofilament test (Target force at foot) ≧ 0.4gms. * 7\. Eastern Cooperative Oncology Group (ECOG) performance status ≦3. * 8\. Grading of peripheral sensory neuropathy in National Cancer Institute- common terminology criteria for adverse events,v5.0 (NCI-CTCAE5) ≧1. * 9\. Written patient informed consent. * 10\. Discontinue analgesics or maintain the same dosage throughout the study period. (e.g., duloxetine, or another analgesia, including Pregabalin, Venlafaxine, Minocycline, Topical gel, Oxycodone, Naloxone, Cannabinoids). Exclusion Criteria: * 1\. Uncontrolled Diabetic Mellitus, HbA1c≧7% is inappropriate(25). * 2\. Diabetic neuropathy diagnosed before receiving chemotherapy. * 3\. Neuropathy from any type of nerve compression (e.g., carpal/tarsal tunnel syndrome, radiculopathy, spinal stenosis, brachial plexopathy). * 4\. Other diseases that cause peripheral neuropathy (e.g., Severe chronic kidney disease, hepatitis, thyroid disorders, vitamin B12 deficiency, viral infections such as HIV and syphilis, alcohol poisoning, inflammatory diseases such as chronic demyelinating polyneuropathy, heavy metal poisoning, hereditary neuropathies). * 5\. Limb trauma that has resulted in vascular and nerve damage. * 6\. Individuals with severe mental illness or cognitive impairments who are unable to provide informed consent. * 7\. Severe hemorrhagic coagulopathy or bleeding tendency. * 8\. Unstable cardiovascular disease. * 9\. Severe skin lesions around the treatment sites. * 10\. Pregnant and breastfeeding women. * 11\. Participants who are concurrently enrolled in additional clinical trials. * 12\. Individuals allergic to topical menthol. * 13\. Adults weighing less than 50 kilograms. * 14\. The researchers will exclude any participants considered to be inappropriate for the study. * 15\. Profound weight loss (\>5% to 10% of body weight).

Outcomes

Primary Outcomes

The Numeric Rating Scale (NRS) of hypoesthesia

Time frame: The NRS of hypoesthesia will be assessed at Baseline (Day 1), Day 14 (end of intervention), Day 21, and Day 28 (end of study).

Secondary Outcomes

The Numeric Rating Scale (NRS) of dysesthesia

Time frame: The NRS of dysesthesia will be assessed at Baseline (Day 1), Day 14 (end of intervention), Day 21, and Day 28 (end of study).

The Numeric Rating Scale (NRS) of allodynia

Time frame: The NRS of allodynia will be assessed at Baseline (Day 1), Day 14 (end of intervention), Day 21, and Day 28 (end of study).

BPI-SF;the Brief Pain Inventory-Short Form

Change from baseline in average pain severity and pain interference scores, as assessed by the Brief Pain Inventory-Short Form (BPI-SF). The BPI-SF average pain severity score utilizes a 0-10 numeric rating scale, ranging from 0 (no pain) to 10 (worst pain), where higher scores indicate a greater degree of pain. The BPI-SF also measures pain interference across seven daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life), with each item scored from 0 (no interference) to 10 (interferes completely).

Time frame: BPI-SF will be assessed at Baseline (Day 1), Day 14 (end of intervention), and Day 28 (end of follow-up).

Von Frey Monofilament Test

Von Frey monofilaments (Semmes-Weinstein von Frey Aesthesiometer, Stoelting Co., Wood Dale, IL, USA):a set of 20 von Frey monofilaments with evaluator size/target forces ranging from 1.65/0.008 g to 6.65/300 g. Each monofilament was calibrated to a target force in grams (g) within a 5% standard deviation. Measurement sites included the sole, tip of the big toe, palm, and tip of the middle finger. All tests were performed by an independent assessor who was blinded to the allocation of randomization. All the procedures followed the operation manual provided by the filament manufacturer.

Time frame: Von Frey Monofilament Test will be assessed at Baseline (Day 1), Day 14 (end of intervention), Day 21, and Day 28 (end of study).

Functional Assessment of Cancer Therapy-General (FACT-G)

Change from baseline in health-related quality of life, as assessed by the 27-item FACT-G questionnaire. Scoring and proration for missing items will be performed according to the official FACIT scoring guidelines. The scale covers four primary domains: Physical Well-Being, Social/Family Well-Being, Emotional Well-Being, and Functional Well-Being. Each item is scored on a 5-point Likert scale ranging from 0 to 4, with higher total adjusted scores indicating better quality of life.

Time frame: FACT-G will be assessed at Baseline (Day 1), Day 14 (end of intervention), and Day 28 (end of follow-up).

Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT-Ntx) Subscale

Change from baseline in chemotherapy-induced peripheral neurotoxicity symptoms, as assessed by the 13-item FACT-Ntx subscale (part of the FACT/GOG-NTX-13 evaluation). Scoring and proration for missing items will be performed according to the official FACIT scoring guidelines. Each item is scored on a 5-point Likert scale ranging from 0 to 4, with higher total adjusted scores indicating fewer neurotoxicity symptoms and better neurological function.

Time frame: FACT-Ntx will be assessed at Baseline (Day 1), Day 14 (end of intervention), and Day 28 (end of follow-up).

Topical Herbal Medicine for Chemotherapy-Induced Peripheral Neuropathy

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes