Neural and Immune Correlates of CIPN and Possible Analgesic Effect of Non-invasive Motor Cortex Stimulation

NCT ID: NCT06522685

Last Updated: 2025-02-06

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-03-01
• Study Completion Date: 2029-06-30

Brief Summary

Over half of cancer patients receiving common chemotherapy treatments experience painful nerve damage called chemotherapy-induced peripheral neuropathy (CIPN). Non-Hispanic Black (NHB) patients are more likely to suffer from this condition and more often need to reduce their chemotherapy doses compared to Non-Hispanic White (NHW) patients.

Currently, only one medication, duloxetine, is approved for treating CIPN, but it doesn't work for everyone. A new approach, transcranial direct current stimulation (tDCS), shows promise as a safe and effective treatment. tDCS can be done at home and reduces the need for hospital visits.

Research indicates that tDCS can improve pain responses in the brain's pain control network. There are differences in pain sensitivity and brain activity related to pain between NHB and NHW individuals, which may influence the effectiveness of treatments.

This research aims to conduct a study to:

1. Test if tDCS is a helpful treatment for painful CIPN.

2. Investigate how CIPN affects brain function in NHB and NHW patients.

3. Examine the role of inflammation in CIPN and its connection to pain severity and brain function.

The investigators expect that NHB patients will benefit more from tDCS due to differences in their brain's pain response system. This project aims to address health disparities and improve outcomes for urban communities, particularly in Baltimore.

Detailed Description

More than half of patients treated with commonly used platinum- and taxane-based anti-cancer agents suffer painful chemotherapy-induced peripheral neuropathy (CIPN). Non-Hispanic Black (NHB) patients have a greater risk (risk ratio=1.6-2.4) of experiencing clinically relevant CIPN and consequent chemotherapy dose reductions compared to non-Hispanic Whites (NHWs). Despite the greater risk of painful CIPN in NHB cancer patients, clinical trials in patients suffering with CIPN have historically included homogeneous patient populations of NHWs. Only duloxetine is approved to treat painful CIPN and is not effective for or tolerated by all patients. Transcranial direct current stimulation (tDCS) of the motor cortex is emerging as a promising, safe, and effective intervention for the pain of neuropathy. An additional benefit of tDCS is that it can be administered at home and supervised remotely, minimizing stressful visits to a hospital venue for treatment. A recent randomized experimental study in healthy individuals completed by the PI showed that one 20-minute session of motor cortex tDCS reduced capsaicin-induced hyperalgesia. To understand the mechanism of pain ameliorating effects of motor cortex tDCS, the PI found enhanced neurophysiological responses of the descending pain modulatory network (DPMN), a group of brain structures activated in response to painful stimuli, after active compared to sham stimulation. Previous investigations have observed differences in opioid receptor binding and pain responses in the DPMN (notably the cingulate cortex and ventral striatum) between healthy NHBs and NHWs as well as differences in pain sensitivity. Likely relevant to the mechanism of CIPN, PET scanning of chemotherapy patients reveals neuroinflammation throughout the brain. The facts that 1) NHB individuals experience a greater rate of CIPN, but have not been represented in relevant clinical studies, 2) non-invasive tDCS is emerging as a safe and effective treatment for neuropathic pain and can be implemented in the home 3) the DPMN is implicated in central pain responses and is activity is enhanced after tDCS and 4) neuroinflammation likely plays a role in CIPN have led us to the present research plan. The overarching goal of this proposal to conduct an exploratory double-blind randomized controlled trial (RCT) addressing 3 specific aims: 1) determine the feasibility and efficacy of active tDCS targeting motor cortex as an analgesic and antihyperalgesic intervention in patients with painful CIPN, 2) determine structural and functional brain correlates of painful CIPN in the DPMN in NHBs and NHWs, and 3) determine inflammatory mediators in patients with painful CIPN and their relationship to the severity of painful CIPN and DPMN structure and function. The investigators expect NHB subjects will experience greater therapeutic effects of tDCS compared to NHW subjects, since NHBs have a dysregulated DPMN potentially affected by neuroinflammation. The goals of this project align with the mission of RCMI@Morgan to understand and combat urban health disparity issues in the City of Baltimore and elsewhere.

Conditions

Chemotherapy-induced Peripheral Neuropathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DEVICE_FEASIBILITY
• Blinding Strategy: TRIPLE

Study Groups

Left motor cortex targeted anodal transcranial direct current stimulation

Active left motor cortex targeted anodal transcranial direct current stimulation at 2 milliamperes applied for 20 minutes once daily on Monday through Friday for two consecutive weeks.

Group Type: EXPERIMENTAL

transcranial direct current stimulation Soterix REMOTE 1x1 miniCT

Intervention Type: DEVICE

Soterix Medical REMOTE Neuromodulation is the only system with device, accessories, and software designed for deployed use. Safe transcranial Electrical Stimulation requires advanced systems designed for consistency and control. REMOTE Neuromodulation is the only system designed from the ground up to allow translation of clinical tES, including tDCS protocols, to diverse deployed environments, while maintaining medical standards.

Left motor cortex targeted sham transcranial direct current stimulation

Active left motor cortex targeted anodal transcranial direct current stimulation at 0 milliamperes applied for 20 minutes once daily on Monday through Friday for two consecutive weeks. The sham consists of a ramp up to 2 mA and immediate ramp down to 0 mA at the beginning of the 20 minute period and a ramp up to 2 mA and immediate ramp down to 0 mA at the end of the 20 minute period.

Group Type: SHAM_COMPARATOR

transcranial direct current stimulation Soterix REMOTE 1x1 miniCT

Intervention Type: DEVICE

Soterix Medical REMOTE Neuromodulation is the only system with device, accessories, and software designed for deployed use. Safe transcranial Electrical Stimulation requires advanced systems designed for consistency and control. REMOTE Neuromodulation is the only system designed from the ground up to allow translation of clinical tES, including tDCS protocols, to diverse deployed environments, while maintaining medical standards.

Interventions

transcranial direct current stimulation Soterix REMOTE 1x1 miniCT

Soterix Medical REMOTE Neuromodulation is the only system with device, accessories, and software designed for deployed use. Safe transcranial Electrical Stimulation requires advanced systems designed for consistency and control. REMOTE Neuromodulation is the only system designed from the ground up to allow translation of clinical tES, including tDCS protocols, to diverse deployed environments, while maintaining medical standards.

Intervention Type: DEVICE

Other Intervention Names

tDCS; Soterix REMOTE 1x1 miniCT

Eligibility Criteria

Inclusion Criteria

• Able to read, write, and comprehend English
• Non-Hispanic White or Non-Hispanic Black
• Stable medication dosage over previous 4 weeks
• Completed primary surgery or chemotherapy for cancer at least 3 months prior to signing consent form
• Diagnosed with painful chemotherapy-induced neuropathy

Exclusion Criteria

• Chronic pain due to another painful condition (e.g., fibromyalgia, chronic low back pain, etc.)
• Any neurological deficits (e.g., lower extremity weakness or bowel/bladder dysfunction, etc.)
• Deficient folate levels (<7 nmol/ml serum)
• Deficient vitamin B12 levels (<200 pg/mL serum)
• Deficient Vitamin D levels (<50 nmol/L or <20 ng/ml)
• Comorbidities affecting sensorimotor function (e.g., multiple sclerosis, diabetes, etc.)
• Unstable mental health condition (acute medical management/hospitalization in the past 6 mo.)
• Elevated hemoglobin A1c levels indicative of uncontrolled diabetes (>6.5%)
• Self-reported Substance abuse (current)
• Drug test positive for illicit drugs except THC
• Excessive alcohol consumption defined as: 1) More than 3 glasses of wine a day; 2) More than 3 beers a day; 3) More than 60 mL of hard liquor a day
• Presence of cardiac pacemaker or automatic implantable cardioverter-defibrillator (AICD).
• Pregnancy, lactation (will be screened with urine pregnancy test)
• Non-removable metal or tattoos around head, excepting dental appliances and fillings
• Use of implantable copper birth control device
• History of frequent severe headaches
• Unstable coronary artery disease
• Uncontrolled Seizure disorder
• Uncontrolled hypertension
• Stage IV cancer

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Maryland, Baltimore

OTHER

Sponsor Role: collaborator

Morgan State University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Cynthia Renn

Baltimore, Maryland, United States

Morgan State University

Baltimore, Maryland, United States

Countries

United States

Central Contacts

Timothy J Meeker, PhD

Role: CONTACT

timothy.meeker@morgan.edu

443-885-4468

Cynthia Renn, PhD

Role: CONTACT

renn@umaryland.edu

410-706-5736

Facility Contacts

Cynthia Renn, PhD

Role: primary

renn@umaryland.edu

410-706-5736

Timothy J Meeker, PhD

Role: primary

timothy.meeker@morgan.edu

443-885-4468

Other Identifiers

HP-00111489

Identifier Type: -

Identifier Source: org_study_id