Integrative Medicine for Chemotherapy-Induced Peripheral Neuropathy

Impact of Integrative Medicine on Chemotherapy-Induced Peripheral Neuropathy: A Multi-centered, Randomized Controlled Trial

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and often debilitating complication of cancer treatments. There is presently no known treatment which can prevent the onset of CIPN, with treatment of existing symptoms limited to reducing the dose intensity of the offending agent. Clinical research has shown that complementary/integrative medicine (CIM) modalities such as acupuncture and reflexology may be effective in relieving CIPN-related symptoms. The present study will included 120 patients suffering from CIPN-related symptoms, and will take place at 3 medical centers in Israel which provide CIM treatments to oncology and hemato-oncology patients. Participants will be allocated to either the control arm (standard conventional supportive care; n=40) or to the intervention arm of the study (standard care with CIM treatments; n=80), based on their preference. Patients in the treatment arm of the study will be randomly allocated to either twice-weekly, single modality acupuncture treatments (n=40), or to a multi-modality treatment program (n=40), which will include acupuncture and additional CIM modalities (i.e., manual-movement and mind-body therapies), for a 6-week period.

The effect of CIM treatments in reducing the severity of CIPN-related symptoms will be assessed at baseline and at 6- and 9-week follow-up visits, using the Functional Assessment of Cancer Therapy -Taxane (FACT-Tax) tool; the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - C30 (EORTC QLQ-C30); and the Measure Yourself Concerns and Well-being (MYCAW) questionnaire. Interim assessment of symptom severity will be conducted by the study nurse throughout the study period, through either telephone or e-mail. Additional study outcomes will include the safety of the CIM treatments; QOL-related concerns which may affect CIPN-related symptoms (e.g., anxiety, depression, sleep disturbances, etc.), as well as issues related to body image and coping with CIPN; physiological assessment of CIPN using a von Frey test (with hairs of varying diameters to assess the threshold for touch evoked sensations); and adherence to the planned oncology treatment regimen, as measured by the Relative Dose Intensity (RDI) calculation.

Study Overview

• Status: Recruiting
• Conditions: Chemotherapy-induced Peripheral Neuropathy
• Intervention / Treatment: Other: Acupuncture; Other: Multi-modality (Acupuncture "plus")

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Noah Samuels, MD; Phone Number: 972-3-5307327; Email: noah.samuels@sheba.health.gov.il

Study Locations

• Israel
  • Ramat Gan, Israel, 52621
    • Recruiting
    • Chaim Sheba Medical Center
    • Contact: Noah Samuels, MD; Phone Number: 972-3-5307327; Email: noah.samuels@sheba.health.gov.il

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:

• Female patients with breast or gynecological cancers who are undergoing a treatment regimen which includes taxane-based chemotherapy (e.g., Paclitaxel, Docetaxel); or
• Patients of either gender with hematological malignancies who are undergoing a treatment regimen which includes neuropathy-inducing agents (e.g., bortezumab for multiple myeloma, etc.).
• Eligible patients will report altered sensations and/or pain in the areas of the feet and or hands, with a score of ≥ 2 (moderate-to-severe) for chemotherapy-induced peripheral neuropathy on the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events - version 4.0 (CTC-AE.v-4.0)
• The onset of CIPN-related symptoms must be recent, following a recently-administered course of chemotherapy and with symptoms appearing no more than a month prior to study recruitment.

Patients must be able to comply with the study protocol, which includes weekly follow-up visits, either in person or by phone; completion of the study questionnaires, in accordance with the study protocol; and, for patients in the treatment arm of the study, attending twice-weekly CIM treatment sessions.

Exclusion Criteria:

- Patients not fulfilling the inclusion criteria, or those with a history of chronic medical conditions which predispose to the development of CIPN (e.g., diabetes mellitus, alcohol abuse), will be ineligible for participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control Group; The control group will consist of patients who choose not to undergo CIM treatments for their CIPN-related symptoms. Participants in this arm of the study will receive standard conventional supportive care, as provided by their oncology health care professionals (HCPs), and closely monitored for any changes in the severity of their CIPN-related symptoms.
Active Comparator: Intervention Group A: Single Modality (acupuncture); Patients choosing to undergo CIM treatments, in addition to standard conventional care: Acupuncture x2/week, for 6 weeks.	Other: Acupuncture; Acupuncture treatments will be patient-tailored, with the acupuncture points (acu-points) to be selected by the acupuncturist at each treatment session, in accordance with the dynamic of the patient's symptoms, concerns and expectations. At the same time, acupuncturists will be required to choose at least 5 of the following 11 acupoints, which are to be incorporated into their treatment regimen: Lower limb points: Liver (LIV) 3, Spleen (SP) 4, SP6, Stomach (ST) 36, Gallbladder (GB) 34, Kidney (KID) 3, LIV8, Web (Bafeng) points Upper limb points: Large Intestine (LI) 4, LI 11, LI10, Pericardium (PC) 6, Triple Warmer (TW) 3/4/5
Active Comparator: Intervention Group B: Multi-modality (acupuncture "plus"); Patients choosing to undergo CIM treatments, in addition to standard conventional care: Acupuncture with additional CIM treatment modalities, x2/week, for 6 weeks.	Other: Acupuncture; Acupuncture treatments will be patient-tailored, with the acupuncture points (acu-points) to be selected by the acupuncturist at each treatment session, in accordance with the dynamic of the patient's symptoms, concerns and expectations. At the same time, acupuncturists will be required to choose at least 5 of the following 11 acupoints, which are to be incorporated into their treatment regimen: Lower limb points: Liver (LIV) 3, Spleen (SP) 4, SP6, Stomach (ST) 36, Gallbladder (GB) 34, Kidney (KID) 3, LIV8, Web (Bafeng) points Upper limb points: Large Intestine (LI) 4, LI 11, LI10, Pericardium (PC) 6, Triple Warmer (TW) 3/4/5; Other: Multi-modality (Acupuncture "plus"); A number of additional CIM treatment modalities will be added to the acupuncture treatment in this arm of the study, in accordance with the practitioners available at each of the participating study centers. These will include one of more of the following: Manual-movement therapies - e.g. acupressure/reflexology, self- and caregiver-practiced acupressure; Mind-body therapies - e.g. relaxation/imagery method, Anthroposophic music therapy The multimodal CIM treatment regimen will be re-evaluated at each session, and adapted according to the concerns and expectations of the patients, as well as the recommendation of the treating CIM practitioner.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptom Severity(neuropathy): Functional Assessment of Cancer Therapy -Taxane (FACT-Tax) tool	CIPN-related symptoms	Up to 9 weeks
Symptom Severity(neuropathy): European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)	CIPN-related symptoms	Up to 9 weeks
Symptom Severity(neuropathy): Measure Yourself Concerns and Well-being (MYCAW) questionnaire:	CIPN-related symptoms	Up to 9 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptom Severity(additional concerns): Functional Assessment of Cancer Therapy -Taxane (FACT-Tax) tool	Additional QOL-related concerns	Up to 9 weeks
Symptom Severity(additional concerns): European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)	Additional QOL-related concerns	Up to 9 weeks
Symptom Severity(additional concerns): Measure Yourself Concerns and Well-being (MYCAW) questionnaire:	Additional QOL-related concerns	Up to 9 weeks
Symptom Severity(neuropathy): Physiological Assessment of CIPN Severity	The von Frey test (Semmes Weinstein Monofilament Set, Bioseb In Vivo Research Instruments, France/USA).	Up to 9 weeks
Adherence to Chemotherapy Regimen: Relative Dose Intensity (RDI)	RDI = Dose Administered (mg) / Interval between treatments (days) ÷ Planned Dose (mg) / Planned Interval between treatments (days)	After 9 weeks
Adverse Effects Associated with CIM treatments	Registering of any adverse events believed to be related to the study intervention treatments	After 9 weeks

Collaborators and Investigators

• Sponsor: The Chaim Sheba Medical Center
• Collaborators: Bnai Zion Medical Center; Carmel Medical Center; Lin Medical Center, Haifa
• Investigators: Principal Investigator: Elad Schiff, MD, Bnai Zion Medical Center, Haifa; Principal Investigator: Eran Ben-Arye, MD, Lin Medical Center, Haifa

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2018
• Primary Completion (Anticipated): March 31, 2022
• Study Completion (Anticipated): March 31, 2022

Study Registration Dates

• First Submitted: September 13, 2017
• First Submitted That Met QC Criteria: September 19, 2017
• First Posted (Actual): September 25, 2017

Study Record Updates

• Last Update Posted (Actual): August 3, 2021
• Last Update Submitted That Met QC Criteria: August 2, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases
• Other Study ID Numbers: 4462-17-SMC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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