Duloxetine + Neurofeedback for Peripheral Neuropathy

Recruiting at 1 trial location

Overseen By Sarah Prinsloo

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Antipsychotics, Duloxetine

Disqualifiers: CNS disease, Bipolar, Schizophrenia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

Duration: 5 weeks

380 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining duloxetine, a medication for nerve pain, with neurofeedback training, a type of brainwave therapy, is more effective at treating chemotherapy-induced peripheral neuropathy than either treatment alone. The researchers aim to determine if this combination can better relieve pain and discomfort from nerve damage. It suits those who have experienced chemotherapy-induced nerve pain for at least three months and do not plan to change their pain medication soon. Participants should be ready to attend therapy sessions at a cancer center or participate from home if they live within a 45-minute drive of a main campus. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to benefit from a potentially effective new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot change your pain medication regimen during the study. You also cannot be taking antipsychotic medications or duloxetine for peripheral neuropathy.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that duloxetine is generally safe for people. In studies with patients experiencing nerve pain from diabetes, duloxetine proved more effective than a placebo. Serious side effects were rare, indicating that duloxetine is usually well-tolerated.

Studies indicate that neurofeedback training is a safe method to manage pain, including nerve pain from chemotherapy. Non-invasive techniques like neurofeedback have been found safe and practical for treating nerve damage caused by chemotherapy.

Overall, previous studies have shown that both treatments in this trial are safe and well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the potential of combining duloxetine with neurofeedback training for treating peripheral neuropathy. Unlike standard treatments that primarily focus on managing symptoms through medications like gabapentin or pregabalin, this approach offers a novel mechanism by integrating neurofeedback, which aims to retrain the brain's response to pain. Duloxetine, a serotonin-norepinephrine reuptake inhibitor (SNRI), is already known for its effectiveness in managing pain and mood symptoms, but when paired with neurofeedback, it could potentially enhance pain relief and improve quality of life more effectively. This combination treatment may provide a more holistic approach by addressing both the neurological and psychological aspects of peripheral neuropathy.

What evidence suggests that this trial's treatments could be effective for peripheral neuropathy?

Research has shown that duloxetine, which participants in this trial may receive, can significantly reduce pain in patients with nerve damage caused by chemotherapy, with 59% of patients experiencing relief. This medication increases certain chemicals in the brain that help manage pain. Neurofeedback training, another treatment option in this trial, teaches patients to control their brain activity and has shown promise in reducing pain and improving quality of life for those with chronic pain. This trial will test the combination of duloxetine with neurofeedback, as studies suggest that this combination might be more effective than using either treatment alone. Both treatments offer hope for better managing nerve pain in people affected by chemotherapy. ^{1 2 4 6 7}

Who Is on the Research Team?

Sarah Prinsloo

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients who have nerve damage (peripheral neuropathy) caused by chemotherapy. They must have had symptoms for at least 3 months, not be changing pain meds during the study, and can't already be taking duloxetine for neuropathy. Participants should understand English, consent to the study's requirements, and either visit a cancer center or agree to remote sessions if living within a 45-minute drive of one.

Inclusion Criteria

My pain level is 4 or higher, or I have nerve pain rated from mild to severe.

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

I have been diagnosed with bipolar disorder or schizophrenia.

I am currently taking antipsychotic medication.

I am aware of any reasons I shouldn't receive DL treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive neurofeedback training and/or duloxetine for 5 weeks

5 weeks

3-5 visits per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Follow-up at 6 and 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Duloxetine
• Neurofeedback Training

Trial Overview The trial tests whether combining duloxetine—a drug that helps with depression and nerve pain—with neurofeedback training improves peripheral neuropathy more than each treatment alone. Neurofeedback uses brain wave monitoring to potentially reduce neuropathy symptoms and improve life quality.

How Is the Trial Designed?

Group I: Group III (duloxetine) Experimental Treatment 3 Interventions

Patients receive duloxetine PO QD for 5 weeks in the absence of unacceptable toxicity.

Group II: Group II (neurofeedback training) Experimental Treatment 3 Interventions

Patients receive neurofeedback training over 1 hour 3-5 times weekly for up to 5 weeks.

Group III: Group I (neurofeedback training, duloxetine) Experimental Treatment 4 Interventions

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.

Duloxetine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Cymbalta for:

• Major Depressive Disorder
• Generalized Anxiety Disorder
• Fibromyalgia
• Neuropathic Pain
• Chronic Musculoskeletal Pain

Approved in European Union as Cymbalta / Yentreve for:

• Major Depressive Disorder
• Generalized Anxiety Disorder
• Diabetic Peripheral Neuropathic Pain
• Fibromyalgia
• Stress Urinary Incontinence

Approved in Canada as Cymbalta for:

• Major Depressive Disorder
• Generalized Anxiety Disorder
• Fibromyalgia
• Neuropathic Pain
• Chronic Musculoskeletal Pain

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Duloxetine hydrochloride, at a fixed dose of 60 mg twice daily, was found to be safe and well tolerated over a 52-week period for patients with diabetic peripheral neuropathic pain (DPNP), showing no significant adverse effects compared to routine care.

Patients receiving routine care experienced a higher rate of serious adverse events, while duloxetine did not negatively impact glycemic control, lipid profiles, or nerve function, indicating its potential as an effective long-term treatment option for DPNP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duloxetine versus routine care in the long-term management of diabetic peripheral neuropathic pain. Raskin, J., Smith, TR., Wong, K., et al.[2022]

In a study of 398 first-time duloxetine users, 78.9% reported experiencing at least one adverse drug reaction (ADR), indicating that while duloxetine is generally safe, side effects are common.

Three new potential safety signals were identified, including amenorrhea, shock-like paraesthesias, and micturition problems, suggesting the need for further evaluation of these effects in future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensive monitoring of duloxetine: results of a web-based intensive monitoring study. Härmark, L., van Puijenbroek, E., van Grootheest, K.[2022]

Duloxetine is effective in providing at least 50% pain relief for patients with painful diabetic neuropathy and fibromyalgia, with a number needed to treat (NNT) of approximately 6, based on a review of six trials involving 1,696 patients over 12 to 13 weeks.

While duloxetine showed fewer withdrawals due to lack of efficacy compared to placebo, it did lead to more withdrawals due to adverse events, such as nausea and somnolence, indicating that while it is effective, some patients may experience side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duloxetine for painful diabetic neuropathy and fibromyalgia pain: systematic review of randomised trials. Sultan, A., Gaskell, H., Derry, S., et al.[2022]

Duloxetine has been shown to be effective in managing painful diabetic neuropathy (PDN), demonstrating significant benefits over placebo and pregabalin based on a systematic review of 23 studies, 8 of which were of high quality.

While duloxetine was effective compared to placebo, its superiority over amitriptyline and pregabalin needs further investigation, as current evidence is limited to only one trial for each comparison.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duloxetine in Painful Diabetic Neuropathy: A Systematic Review. Hossain, SM., Hussain, SM., Ekram, AR.[2022]

Duloxetine is now FDA-approved for the treatment of diabetic peripheral neuropathic pain (DPNP), marking a significant advancement in managing this condition that affects some patients with diabetic peripheral neuropathy (DPN).

Duloxetine not only alleviates pain associated with DPNP but also helps address depression, functioning through its mechanism of inhibiting the reuptake of norepinephrine and serotonin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diabetic peripheral neuropathic pain: recognition and management. Cole, BE.[2015]

A systematic review of seven randomized controlled trials involving 645 patients found that duloxetine was not significantly more effective than placebo for both the treatment and prevention of chemotherapy-induced peripheral neuropathy (CIPN).

The safety profile of duloxetine was also similar to that of placebo, indicating that there is currently limited evidence to support its use in CIPN, highlighting the need for more rigorous studies in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duloxetine for prevention and treatment of chemotherapy-induced peripheral neuropathy (CIPN): systematic review and meta-analysis. Chow, R., Novosel, M., So, OW., et al.[2023]

Duloxetine at a fixed dose of 60 mg twice daily is safe for long-term use (up to 52 weeks) in managing diabetic peripheral neuropathic pain (DPNP), with no significant differences in serious adverse events compared to routine care.

Patients treated with duloxetine showed significant improvements in quality of life measures, including physical functioning and pain relief, while experiencing a higher incidence of asthenia, but no adverse effects on lipid profiles or nerve function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open-label 52-week clinical extension comparing duloxetine with routine care in patients with diabetic peripheral neuropathic pain. Wernicke, JF., Wang, F., Pritchett, YL., et al.[2022]

Duloxetine, administered at either 60 mg twice daily or 120 mg once daily, was found to be safe and well-tolerated in 449 patients with diabetic peripheral neuropathic pain over a 28-week period, with low rates of discontinuation due to adverse events.

Both dosages of duloxetine resulted in significant improvements in pain relief, as measured by the Brief Pain Inventory and Clinical Global Impression of Severity scales, indicating its efficacy in treating diabetic peripheral neuropathic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duloxetine for patients with diabetic peripheral neuropathic pain: a 6-month open-label safety study. Raskin, J., Wang, F., Pritchett, YL., et al.[2022]

Duloxetine hydrochloride has been shown to effectively reduce diabetic peripheral neuropathic pain at doses of 60 mg/day and 120 mg/day, with minimal to moderate side effects, making it a viable treatment option for patients.

The medication has minimal impact on glycemic control and does not adversely affect lipid or cardiovascular parameters, indicating it is safe for use in diabetic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintaining efficacy in the treatment of diabetic peripheral neuropathic pain: role of duloxetine. Zilliox, L., Russell, JW.[2021]

Duloxetine, a medication for diabetic peripheral neuropathic pain, showed significant pain reduction in Chinese patients at weeks 1, 2, and 4, although the overall primary endpoint was not statistically significant after 12 weeks.

The safety profile of duloxetine was consistent with previous studies, with common side effects including nausea and somnolence, indicating it is generally safe for use in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duloxetine versus placebo in the treatment of patients with diabetic neuropathic pain in China. Gao, Y., Ning, G., Jia, WP., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10711341/

Duloxetine for treating painful neuropathy, chronic pain or ... In diabetic peripheral neuropathic pain, a 50% or better improvement with duloxetine 60 mg per day was just over one and a half times more likely than with ...

2. cochranelibrary.com cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007115.pub2/abstract

Duloxetine for treating painful neuropathy or chronic pain In diabetic peripheral neuropathic pain the relative rate of 50% improvement with duloxetine 60 mg per day was just over one and a half times ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10031998/

Efficacy and safety of duloxetine in painful diabetic peripheral ... Furthermore, 45.6% and 64.5% of all patients experienced 50% and 30% pain reduction, respectively, which highlights the clinical efficacy of ...

4. onclive.com onclive.com/view/study-finds-cymbalta-reduces-peripheral-neuropathy-pain

Study Finds Cymbalta Reduces Peripheral Neuropathy Pain The antidepressant duloxetine (Cymbalta) relieved pain associated with chemotherapy-induced peripheral neuropathy for 59% of patients in a phase III study.

5. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2020.554899/full

A Systematic Review of Efficacy, Safety, and Tolerability ... Statistically significant results were obtained in seven studies, where duloxetine improved symptomatology, reducing the pain impact registered by BPI. In ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT00844194

Duloxetine in Patients With Diabetic in Peripheral ... To monitor safety and tolerability, treatment discontinuation rates, treatment emergent adverse events, change in vital signs, laboratory results and suicidal ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2017.35.31_suppl.236

Long-term efficacy and safety of duloxetine in the ... Twenty-five (92.5%) of the 27 patients showed decreased pain after the use of duloxetine. Mean duration of treatment was 29 weeks (range, 1~130 ...