Duloxetine and Neurofeedback Training for the Treatment of Chemotherapy Induced Peripheral Neuropathy

Study Overview
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Brief Summary
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This phase II trial investigates how well duloxetine and neurofeedback training work in treating patients with chemotherapy induced peripheral neuropathy. Duloxetine is a type of serotonin and norepinephrine reuptake inhibitor that increases the amount of certain chemicals in the brain that help relieve depression and peripheral neuropathy. Neurofeedback training is a type of therapy that uses an electroencephalograph (EEG) and a computer software program to measure brain wave activity and may help teach patients with peripheral neuropathy (nerve damage) how to change their own brain waves to lower their feelings of neuropathy and help improve their overall quality of life. Giving duloxetine and neurofeedback training may work better in treating peripheral neuropathy caused by chemotherapy compared to duloxetine or neurofeedback training alone.

Detailed Description
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PRIMARY OBJECTIVE: I. Determine if the combination of duloxetine (DL) and neurofeedback (NFB) is superior to DL or NFB alone in treating chemotherapy induced peripheral neuropathy (CIPN). SECONDARY OBJECTIVES: I. Determine the optimal number of neurofeedback sessions needed to result in long-term relief of CIPN in a large cohort of cancer survivors and across socioeconomic groups. II. Examine baseline brain signatures as a predictor of response to neurofeedback (NFB) and to duloxetine and determine who will require more sessions of NFB to achieve relief of symptoms. III. Examine if the combination of DL + NFB (than those getting DL or NFB alone) or a larger number of NFB sessions results in better improvements in cancer-related symptoms, physical functioning, and quality of life (QOL). OUTLINE: Patients are randomized to 1 of 3 groups. GROUP I: Patients receive neurofeedback training over 1 hour each 3-5 times weekly for up to 5 weeks. Patients also receive duloxetine orally (PO) once daily (QD) for 5 weeks in the absence of unacceptable toxicity. GROUP II: Patients receive neurofeedback training session over 1 hour 3-5 times weekly for up to 5 weeks. GROUP III: Patients receive duloxetine PO QD for 5 weeks in the absence of unacceptable toxicity. After completion of study, patients are followed up at 6 and 12 months.

Official Title
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Optimizing Neurofeedback to Treat Chemotherapy Induced Peripheral Neuropathy

Conditions
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Chemotherapy-Induced Peripheral Neuropathy, Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm

Intervention / Treatment
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* Drug: Duloxetine
* Behavioral: Neurofeedback
* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have the ability to understand and read English, sign a written informed consent, and be willing to follow protocol requirements Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 Pain score >= 4 on a 0-10 numeric pain scale and/or grade 1-4 neuropathic pain according to the National Cancer Institute's 4 point grading scale Neuropathic symptoms must be related to chemotherapy (in the opinion of the treating physician) Patients must have had neuropathic symptoms for a minimum of 3 months No plans to change pain medication regimen during the course of the study Off active chemotherapy treatment for minimum of 3 months Hormonal (e.g., tamoxifen or Arimidex, etc.) and targeted (Tarceva and Avastin, etc.) therapies allowed as long as they will be continued during the course of the study Willing to come to one of the participating cancer centers for the therapy sessions; or willing to participate in the therapy sessions at their homes and live within a 45 minute drive of the main campuses; or can participate in the therapy sessions from MD Anderson regional care centers If participants agree to the Remote Training Option, participants should be willing to receive equipment at their homes and to return the equipment to MDA in case of malfunction or completion of the study If participants agree to the Remote Training Option, participants should be willing to download necessary software to their home computer If participants agree to the Remote Training Option, participants should be willing to allow research staff remote access to their computer to run the neurofeedback program Exclusion Criteria: Patients who are taking any antipsychotic medications Patients with active central nervous system (CNS) disease, such as clinically-evident metastases or leptomeningeal disease, dementia, or encephalopathy Patients who have ever been diagnosed with bipolar disorder or schizophrenia Patients with known, previously diagnosed peripheral neuropathy from causes other than chemotherapy Patients who have a history of head injury or who have known seizure activity Patients for whom any contraindications of DL are known Patients with suicidal ideation Patients who are already taking duloxetine for peripheral neuropathy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group I (neurofeedback training, duloxetine)<br>Patients receive neurofeedback training over 1 hour 3-5 times weekly for up to 5 weeks. Patients also receive duloxetine PO QD for 5 weeks in the absence of unacceptable toxicity. | Drug: Duloxetine<br>* Given PO<br>Behavioral: Neurofeedback<br>* Receive neurofeedback training<br>* Other names: EEG biofeedback;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Experimental: Group II (neurofeedback training)<br>Patients receive neurofeedback training over 1 hour 3-5 times weekly for up to 5 weeks. | Behavioral: Neurofeedback<br>* Receive neurofeedback training<br>* Other names: EEG biofeedback;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Experimental: Group III (duloxetine)<br>Patients receive duloxetine PO QD for 5 weeks in the absence of unacceptable toxicity. | Drug: Duloxetine<br>* Given PO<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Pain Quality Assessment Scale (PQAS) unpleasantness score | The primary analysis will be a linear model comparing the mean difference in the change of the unpleasantness subscale of the (PQAS)Pain Quality Assessment Scale from baseline to the end of treatment (5 weeks) between the combination arm, the duloxetine (DL), and the neurofeedback (NFB) arm while adjusting for the stratification factor. Pain Quality Assessment Scale (0-10) 0-No pain-10 Most Intense Pain Imaginable. | Baseline 5 up to week 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in PQAS unpleasantness score | Will use analysis of covariance (ANCOVA) to evaluate whether chemotherapy induced peripheral neuropathy (CIPN) differs across the three subgroups with 0, 10 or 15 additional sessions of NFB, among the participants from the NFB + DL group who report at least 1-point clinical improvement in CIPN at week 5. The analysis will adjust for the baseline outcome (at week 5), time with CIPN symptoms (minimization factor), and other covariates such as age, sex, cancer stage, time since diagnosis, and cancer type, as appropriate. Pain Quality Assessment Scale (0-10) 0-No pain-10 Most Intense Pain Imaginable. | Baseline 5 up to week 10 | 
| Baseline brain signatures as predictors of response to NFB and to DL | Will perform ANCOVA with the change of the unpleasantness subscale from baseline to week 5 (i.e., end of the first 15 sessions of NFB) as the outcome, intervention (NFB, DL or combo), the brain signature (one at a time) and its interaction with intervention as the independent variables of interest. Pain Quality Assessment Scale (0-10) 0-No pain-10 Most Intense Pain Imaginable. | Up to week 5 | 
| Evaluation of patients who will require more sessions of NFB to achieve relief of symptoms | Linear mixed model (LMM) analyses will be performed using data measured at end of treatment, months 6 and 12 only on patients who report clinical improvement at week 5. | Up to 12 months post-treatment | 
| Change in cancer-related symptoms | ANCOVA and LMM analyses will be performed to evaluate the effect of the number of additional NFB sessions on cancer-related symptoms. | Baseline up to 12 months post-treatment | 
| Change in physical functioning | ANCOVA and LMM analyses will be performed to evaluate the effect of the number of additional NFB sessions on physical functioning. | Baseline up to 12 months post-treatment | 
| Change in quality of life | ANCOVA and LMM analyses will be performed to evaluate the effect of the number of additional NFB sessions on quality of life. | Baseline up to 12 months post-treatment |