Botulinum Toxin A for the Treatment of Chemotherapy Induced Peripheral Neuropathy

NCT03571334 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: ebeddows
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Chemotherapy induced peripheral neuropathy (CIPN) is a common side effect of taxanes and platinum derivative based chemotherapeutic agents, common in breast cancer treatment regimens. It can have a significant effect on both quality of life and treatment outcomes, often resulting in dose modifications and early treatment discontinuation. The use of IncobotulinumtoxinA (INA) ((Xeomin®, Merz) has recently been shown to be effective in the treatment of neuropathic pain via inhibiting the release of several neurotransmitters involved in pain signaling pathway. The purpose of this study is to examine the efficacy and safety of intradermal INA injections for treatment of CIPN in breast cancer patients. The study will recruit a total of 40 participants, randomly assigned to receive either INA (Experimental group, n=20) or saline placebo injections (Control group n=20). Potential participants who have received chemotherapy for breast cancer will be screened for the diagnosis of peripheral neuropathy. After obtaining informed consent, participants will be further screened with the DN4 questionnaire, a clinician administered questionnaire that has a high level of sensitivity and specificity in discriminating neuropathic pain. Those study participants who score ≥4 on this tool will undergo nerve conduction studies to confirm the presence of peripheral neuropathy. Recruited study participants will then be randomized to treatment or control groups; the treatment group will undergo intradermal injections of INA (100 Units INA, total volume 5ml), and the control groups will undergo placebo injection with preservative-free normal saline (equal volume, 5mL). Total injection volume will be divided evenly and injected intradermally into a total of 50 sites on either the feet or hands (25 sites per limb). The primary outcome will be the assessment of pain using the neuropathic pain scale (NPS) prior to intervention and at eight weeks post intervention. Secondary outcomes will include the change in NPS for each domain at additional time points: 2weeks, 4 weeks, 12 weeks, 6 months, the change in the Neuropathic Pain Impact on Quality of Life (NePIQoL) score at time points: 2 weeks, 4 weeks, 8 weeks, 12 weeks, 6 months, and the incidence of treatment related adverse events within each cohort. Statistical analysis will be utilized to determine whether the injection of intradermal INA is effective in improving pain as measured by the NPS scales vs placebo. We hypothesize that the study participants treated with INA will have lower NPS scores as compared to placebo.

Conditions

Peripheral Neuropathy Due to Chemotherapy

Outcome Measures

Primary Outcomes (1)

• Improvement in pain from baseline at eight weeks as measured by the change in Neuropathic Pain Scale (NPS)

  The primary outcome of this study will be the change pain as measured by the NPS at 8 weeks post intervention as compared to baseline NPS scores. The NPS is a validated scale that is used to classify patient's neuropathic pain. It includes assessment of global pain intensity and pain unpleasantness, two items addressing the location of the pain as deep or surface, and six items addressing the specific qualities of neuropathic such as sharp, hot, dull, cold, sensitivity, and itchy.

  baseline and 8 weeks

Secondary Outcomes (4)

• Improvement in pain from baseline as measured by the change in Neuropathic Pain Scale (NPS)

  baseline and 2 weeks, 4 weeks, 12 weeks, 6 months

• Change in pain characteristics as measured by the change in each individual domain of Neuropathic Pain Scale (NPS)

  baseline and 2 weeks, 4 weeks, 8 weeks, 12 weeks, 6 months

• Change in quality of life as measured by the Neuropathic Pain Impact on Quality of Life (NePIQoL) score

  2 weeks, 4 weeks, 8 weeks, 12 weeks, 6 months post intervention

• Safety as measured by self reporting of incidence of treatment related adverse events

  2 weeks, 4 weeks, 8 weeks, 12 weeks, 6 months post intervention

Study Arms (2)

IncobotulinumtoxinA

EXPERIMENTAL

IncobotulinumtoxinA (Xeomin®, Merz) (INA) will be reconstituted with preservative-free normal saline to a dilution of 5mL:100 units. Study participants in this arm will receive 50u INA (total volume 2.5mL) injected into each limb, max 2 limbs per subject (either bilateral hands or bilateral feet.) Hands: INA will be injected across the palmar surface of the digits in a grid like pattern covering a total of 25 sites per limb (0.1mL/site). Feet: INA will be injected across the dorsal surface of the feet also in a grid like pattern covering a total of 25 sites per limb (0.1mL/site).

Drug: IncobotulinumtoxinA (Xeomin®, Merz) (INA)

saline control

PLACEBO COMPARATOR

Study participants in this arm will 2.5mL normal saline injected into each limb, max 2 limbs per subject (either bilateral hands or bilateral feet.) Hands: saline will be injected across the palmar surface of the digits in a grid like pattern covering a total of 25 sites per limb (0.1mL/site). Feet: Saline will be injected across the dorsal surface of the feet also in a grid like pattern covering a total of 25 sites per limb (0.1mL/site).

Drug: Normal saline

Interventions

IncobotulinumtoxinA (Xeomin®, Merz) (INA) DRUG

IncobotulinumtoxinA (Xeomin®, Merz) (INA) will be reconstituted with preservative-free normal saline to a dilution of 5mL:100 units. Study participants will receive 50u INA (total volume 2.5mL) injected into each limb, max 2 limbs per subject (either bilateral hands or bilateral feet.) Study participants will receive one series of injections during the trial. In the hands, INA will be injected across the palmar surface of the digits in a grid like pattern covering a total of 25 sites per limb (0.1mL/site). In the feet, INA will be injected across the dorsal surface of the foot in a grid like pattern covering a total of 25 sites per limb (0.1mL/site). Injections will be performed intradermally using a 5/16-inch, 32-g needle

Also known as: Xeomin® (Brand name)

IncobotulinumtoxinA

Normal saline DRUG

Study participants will total volume 2.5mL of 0.9% Normal saline injected into each limb, max 2 limbs per subject (either bilateral hands or bilateral feet.) Study participants will receive one series of injections during the trial. In the hands, 0.9% Normal saline will be injected across the palmar surface of the digits in a grid like pattern covering a total of 25 sites per limb (0.1mL/site). In the feet, 0.9% Normal saline will be injected across the dorsal surface of the foot in a grid like pattern covering a total of 25 sites per limb (0.1mL/site). Injections will be performed intradermally using a 5/16-inch, 32-g needle

saline control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Been diagnosed with breast cancer and undergone treatment with taxane based chemotherapeutic agents. Patients with metastatic and non metastatic disease are eligible.
• Have neuropathic pain with onset within 6 months of chemotherapy
• Must score \>4 on DN4 scale, a scale with high specificity and sensitivity for differentiating neuropathic pain from somatic and nociceptive pain
• Age \>18 years, male and/or female
• Ability to understand a written informed consent document, and the willingness to sign it.

You may not qualify if:

• End Stage Renal Disease patients on Hemodialysis
• Female participants who are pregnant (positive urine pregnancy test), who have an infant they are breastfeeding, or intend to become pregnant within 6 months.
• History of peripheral neuropathy attributed to any cause other than chemotherapy
• Currently receiving chemotherapy, or having had received chemotherapy in the past 6 months
• Prior treatment with Botulinum Toxin A for any indication within the past 6 months
• Changes in neuropathic pain modulators within 1 month prior to enrollment or during the course of the trial. Participants who require rescue medications for breakthrough pain can be given so at the discretion of their provider.
• Hypersensitivity reaction to INA injection
• Distal muscle weakness and/or atrophy
• Active infection at injection site

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Related Publications (27)

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Related Links

• Botox® \[package insert\]. Irvine, CA: Allergan, Inc; 2011

MeSH Terms

Interventions

incobotulinumtoxinA; Saline Solution

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Central Study Contacts

Erin McGonigle, MD

CONTACT

414-955-1914; emcgonigle@mcw.edu

Meghann Sytsma, BS

CONTACT

414-955-1922; mesytsma@mcw.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: June 11, 2018
• First Posted: June 27, 2018
• Study Start: July 8, 2020
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2024
• Last Updated: December 23, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)