Topical Cannabidiol for the Treatment of Chemotherapy-Induced Peripheral Neuropathy

Topical Cannabidiol (CBD) for the Treatment of Chemotherapy-Induced Peripheral Neuropathy: A Randomized Placebo-Controlled Pilot Trial

This clinical trial compares topical cannabidiol to placebo in improving chemotherapy-induced peripheral neuropathy, or painful sensations in your hands or feet due to chemotherapy. Peripheral neuropathy is a nerve problem that causes pain, numbness, tingling, swelling, or muscle weakness in different parts of the body. It usually begins in the hands or feet and gets worse over time. Peripheral neuropathy caused by chemotherapy is called chemotherapy-induced peripheral neuropathy (CIPN). CIPN is commonly seen in patients receiving certain chemotherapy medications and is hard to treat. Medications commonly used to treat CIPN have limited benefits and may cause significant side effects. A small report showed that topical cannabidiol may help treat neuropathy in patients with diabetes. This study is being done to determine if cannabidiol cream can help improve the symptoms of CIPN.

Study Overview

• Status: Completed
• Conditions: Malignant Solid Neoplasm; Chemotherapy-Induced Peripheral Neuropathy
• Intervention / Treatment: Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Cannabidiol; Drug: Placebo Administration

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate whether topical cannabidiol (CBD) improves CIPN, compared to placebo.

II. To evaluate side effects from topical CBD cream use, compared to placebo.

SECONDARY OBJECTIVES:

I. Other measures of neuropathy as measured by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) CIPN20 motor subscale, the EORTC QLQ CIPN20 autonomic scale, and the total Common Terminology Criteria for Adverse Events (CTCAE) neuropathy scale.

II. Adverse event profiles will also be assessed using symptom questionnaires and CTCAE version (v)5.0.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients apply cannabidiol cream topically to affected areas twice daily (BID) for 14 days. Patients then apply placebo cream topically to affected areas BID for 14 days.

ARM II: Patients apply placebo cream topically to affected areas BID for 14 days. Patients then apply cannabidiol cream topically to affected areas BID for 14 days.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Albert Lea, Minnesota, United States, 56007
      • Mayo Clinic Health System Albert Lea
    • Grand Rapids, Minnesota, United States, 55744
      • Fairview Grand Itasca Clinic and Hospital
    • Hibbing, Minnesota, United States, 55746
      • Fairview Range Medical Center
    • Mankato, Minnesota, United States, 56001
      • Mayo Clinic Health System Mankato
    • Monticello, Minnesota, United States, 55362
      • Monticello Cancer Center
    • Princeton, Minnesota, United States, 55371
      • Fairview Northland Medical Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester
    • Thief River Falls, Minnesota, United States, 56701
      • Sanford Thief River Falls
    • Worthington, Minnesota, United States, 56187
      • Sanford Worthington

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age >= 18 years
• English speaking
• Cancer diagnosis of any tumor type with chemotherapy-induced neuropathy
• At least 4 out of 10 severity of neuropathy pain and/or tingling
• Stable for at least 7 days prior to registration on medications for neuropathy, if any are being used
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2

• Negative pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only

  • NOTE: If a urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Able to provide written informed consent
• Ability to complete questionnaire(s) by themselves or with assistance
• No evidence of residual cancer
• Platelet count > 100,000/mm^3 (following completion of chemotherapy)
• Absolute neutrophil count (ANC) >= 1,000/mm^3 (following completion of chemotherapy)
• Hemoglobin > 11 g/dL (following completion of chemotherapy)
• Serum transaminase (alanine aminotransferase [ALT] or aspartate aminotransferase [AST]) =< 1.2 x upper limit of normal (ULN) (following completion of chemotherapy)
• Alkaline phosphatase =< 1.2 x ULN (following completion of chemotherapy)
• Serum creatinine =< 1.2 x ULN (following completion of chemotherapy)

Exclusion Criteria:

• Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:

  • Pregnant persons
  • Nursing persons
  • Persons of childbearing potential who are unwilling to employ adequate contraception
• Any medical condition that would prohibit use of a topical cream (skin infection or open wound in the area of the neuropathy)
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• Pre-existing neuropathy prior to chemotherapy that would confuse the issue of CIPN
• Currently on chemotherapy or received chemotherapy treatment within the prior 3 months
• Use of other cannabis products within 30 days prior to registration
• History of allergy to cannabis products

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (cannabidiol, placebo); Patients apply cannabidiol cream topically to affected areas BID for 14 days. Patients then apply placebo cream topically to affected areas BID for 14 days.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Drug: Cannabidiol; Applied topically; Other Names: CBD; Epidiolex; CBD Oil; GWP42003-P; Drug: Placebo Administration; Applied topically
Experimental: Arm II (placebo, cannabidiol); Patients apply placebo cream topically to affected areas BID for 14 days. Patients then apply cannabidiol cream topically to affected areas BID for 14 days.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Drug: Cannabidiol; Applied topically; Other Names: CBD; Epidiolex; CBD Oil; GWP42003-P; Drug: Placebo Administration; Applied topically

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Chemotherapy-induced Peripheral Neuropathy (CIPN) From Baseline	CIPN will be measured by the sensory subscale of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-CIPN20 which is composed of 9 individual items. Each item is scored on a 1-to-4 scale, where 1 means "not at all" and 4 means "very much." Higher scores indicate greater severity of symptoms.	Week 1, week 2, week 3, and week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in EORTC QLQ CIPN20 Motor Subscale From Baseline	Motor symptoms of CIPN will be measured by the motor subscale of the EEORTC QLQ-CIPN20 which is composed of 8 individual items. Each item is scored on a 1-to-4 scale, where 1 means "not at all" and 4 means "very much." Higher scores indicate greater severity of symptoms. Will be compared between arms using two-sample, two-sided t-tests. The cannabidiol arm will be compared to the placebo arm. Will construct 95% confidence intervals for the mean difference in sensory neuropathy score between arms. Repeated measures mixed models will be applied to the sensory scores over all time points to determine longitudinal effects and to adjust for confounding factors. Graphical results will include profile plots over time, stream plots of individual changes over time, and forest plots of the 95% confidence intervals by arm.	Week 1, week 2, week 3, and week 4
Change in EORTC QLQ CIPN20 Autonomic Scale From Baseline	Autonomic nervous system symptoms related to CIPN will be measured by the autonomic subscale of the EEORTC QLQ-CIPN20 which is composed of 3 individual items answered on a 4-point scale ranging from "not at all' to "very much." . Higher scores indicate more severe symptoms. Will be compared between arms using two-sample, two-sided t-tests. The cannabidiol arm will be compared to the placebo arm. Will construct 95% confidence intervals for the mean difference in sensory neuropathy score between arms. Repeated measures mixed models will be applied to the sensory scores over all time points to determine longitudinal effects and to adjust for confounding factors. Graphical results will include profile plots over time, stream plots of individual changes over time, and forest plots of the 95% confidence intervals by arm.	Week 1, week 2, week 3, and week 4
Incidence of Adverse Events (AEs)	Incidence of AEs will be reported per arm, assessed using Common Terminology Criteria (CTCAE) version 5.0.	Up to 14 days for each part of a sequence
Incidence of Grade 3 or Higher Adverse Events	Will be assessed using symptom questionnaires and CTCAE version 5.0. Will compare the maximum (worst) values between arms. Fisher's exact tests will be used to compare incidence rates and Wilcoxon rank-sum tests will be used to compare maximum values between arms.	Up to 28 days

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Stacy D. D'Andre, M.D., Mayo Clinic in Rochester

Publications and helpful links

General Publications

• D'Andre S, Novotny P, Walters C, Lewis-Peters S, Thome S, Tofthagen CS, Giridhar KV, Loprinzi C. Topical Cannabidiol for Established Chemotherapy-Induced Neuropathy: A Pilot Randomized Placebo-Controlled Trial. Cannabis Cannabinoid Res. 2024 Dec;9(6):e1556-e1564. doi: 10.1089/can.2023.0253. Epub 2024 Jul 17.

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2022
• Primary Completion (Actual): July 14, 2023
• Study Completion (Actual): July 28, 2023

Study Registration Dates

• First Submitted: May 19, 2022
• First Submitted That Met QC Criteria: May 19, 2022
• First Posted (Actual): May 24, 2022

Study Record Updates

• Last Update Posted (Estimated): January 16, 2026
• Last Update Submitted That Met QC Criteria: December 29, 2025
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Organic Chemicals; Hydrocarbons; Terpenes; Cannabinoids; Cannabidiol
• Other Study ID Numbers: MC211003 (Mayo Clinic in Rochester); NCI-2022-02479 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 21-011969 (Other Identifier: Mayo Clinic Institutional Review Board)

Drug and device information, study documents

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