Cognitive Training for Chemobrain

Overseen By Nicole T Nguyen, MA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Vanderbilt University Medical Center

Must not be taking: Investigational drugs

Disqualifiers: Neurologic, Psychiatric, Cognitive impairment, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a special brain training program can help individuals experiencing "chemobrain," a type of cognitive impairment caused by chemotherapy. Participants will either use a computer-based cognitive training program called Neuroplasticity-based Computerized Cognitive Remediation or engage with educational materials to compare results. The trial seeks individuals diagnosed with breast cancer who underwent chemotherapy 1 to 8 years ago and are experiencing ongoing cognitive issues. Participants should not have active neurological or psychiatric conditions and must be able to read and speak English.

As an unphased trial, this study offers a unique opportunity to contribute to understanding and potentially improving cognitive health after chemotherapy.

Do I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, you can continue using certain CNS active medications, like antidepressants, if your dosage has been stable for at least 3 months.

What prior data suggests that this neuroplasticity-based computerized cognitive remediation is safe for treating chemotherapy-related cognitive impairment?

Research shows that neuroplasticity-based computerized cognitive remediation (nCCR), a type of brain training, is generally safe for people. This training addresses thinking and memory problems, often referred to as "chemobrain," that can occur after chemotherapy. Studies have found that similar brain training methods are usually well-tolerated, with most people not experiencing major side effects. This suggests the treatment is safe for most participants. However, discussing any concerns with the trial team before deciding to join is always advisable. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Neuroplasticity-based Computerized Cognitive Remediation (nCCR) for tackling chemobrain because it takes a unique approach by focusing on improving brain function through neuroplasticity. Unlike traditional treatments that might involve medications to manage cognitive symptoms, this method uses a combination of "Bottom up" and "Top down" training programs to enhance sensory processing and cognitive control. The "Bottom up" training sharpens basic auditory and visual processing, while "Top down" training targets cognitive skills such as attention and verbal strategy. This dual approach aims to directly improve brain function, offering a potentially more effective way to address cognitive issues associated with chemotherapy.

What evidence suggests that Neuroplasticity-based Computerized Cognitive Remediation is effective for chemobrain?

Research has shown that neuroplasticity-based computerized cognitive remediation (nCCR), which participants in this trial may receive, can help with thinking and memory problems related to chemotherapy, often known as "chemobrain." Studies have found that nCCR improves skills like attention and memory through specific brain exercises. For instance, one study found that nCCR was as effective as medication in reducing certain symptoms, but it worked faster. Another study examined a similar program called Neuroflex, which helped cancer survivors improve their focus and clarity of thought. While more detailed information on nCCR's effectiveness for chemobrain is still being gathered, these findings suggest it could benefit cognitive function. Participants in this trial may also be assigned to an Education Comparison Control group, which uses a learning-based approach with DVDs on various topics. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults aged 35-80 who have had breast cancer and received chemotherapy within the last 1-8 years. They must speak English, report ongoing cognitive issues post-treatment, and be medically stable. Exclusions include significant cognitive impairment or dementia, recent investigational drug use, certain unstable conditions, color blindness, unstable psychiatric disorders, and substance abuse history.

Inclusion Criteria

I am between 35 and 80 years old.

I do not have any unstable health conditions.

I have been diagnosed with breast cancer.

Exclusion Criteria

I do not have any major illnesses that would prevent me from following the study's requirements.

My dose for CNS active medications like antidepressants has been stable for 3 months.

I have never had a severe head injury with lasting brain problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo neuroplasticity-based computerized cognitive remediation (nCCR) for chemotherapy-related cognitive impairment over 6 weeks

6 weeks

Follow-up

Participants are monitored for changes in cognitive performance and subjective cognitive complaints after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Education Control Condition
• Neuroplasticity-based Computerized Cognitive Remediation

Trial Overview The study tests a computer program designed to improve thinking skills affected by chemotherapy (nCCR) against an educational control condition. Participants will randomly receive either the nCCR treatment or education sessions to compare effectiveness in treating 'chemobrain'.

How Is the Trial Designed?

Group I: Neuroplasticity-based Computerized Cognitive Remediation Experimental Treatment 1 Intervention

Behavioral: Neuroplasticity-based Computerized Cognitive Remediation The nCCR has two major components: Bottom up and Top down training. * Bottom up" training: The training includes selected tasks from "Brain HQ", a program designed for older adults, that enhances basic processing of sensory stimuli with the goal to improve fidelity of auditory and visual encoding. * Top down training": We designed programs to target cognitive control functions associated with poor treatment response, i.e., initiation and use of verbal strategy and susceptibility to interference. These "Top Down" Programs include a visual attention program, either Catch the Ball or Neurogrow, and a semantic strategy program, Semantic Organization.

Group II: Education Comparison Control Active Control 1 Intervention

The education control condition is a learning-based approach that utilizes DVDs on history, art, science, etc. This active condition is comparable to nCCR in length of exposure, audio-visual presentation, computer use and contact with research staff.

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

University of Utah

Collaborator

Trials

1,169

Recruited

1,623,000+

Published Research Related to This Trial

A pilot study involving 21 breast and gynecologic cancer survivors showed that the Neuroflex cognitive enhancement program is feasible and well-accepted, with participants completing an average of 44.5 hours of training and achieving a 100% completion rate.

Participants reported significant improvements in cognitive function, including verbal learning and memory, as well as mood and disability assessments, suggesting that Neuroflex may effectively address chemotherapy-related cognitive impairment (CRCI).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of focused computerized cognitive training (Neuroflex) to improve symptoms in women with persistent chemotherapy-related cognitive impairment. Vega, JN., Newhouse, PA., Conley, AC., et al.[2023]

Chemotherapy-induced cognitive dysfunction, commonly referred to as 'chemobrain,' affects up to 78% of cancer patients, significantly impacting their quality of life and cognitive abilities such as memory and attention.

The underlying mechanisms of chemobrain are not fully understood, but increased proinflammatory cytokines and oxidative stress are believed to play key roles, alongside potential effects on neurotransmission and neurogenesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Four decades of chemotherapy-induced cognitive dysfunction: comprehensive review of clinical, animal and in vitro studies, and insights of key initiating events. Dias-Carvalho, A., Ferreira, M., Ferreira, R., et al.[2022]

In a study of 180 breast cancer patients, those undergoing chemotherapy (CT+) reported significantly worse perceived cognitive impairment (PCI) compared to those not receiving chemotherapy (CT−), indicating that chemotherapy negatively impacts cognitive function.

Objective measures showed that CT+ patients had decreased cerebral activity in the prefrontal cortex during verbal fluency tasks, supporting the link between chemotherapy and cognitive deficits, particularly in executive functioning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy-Related Cognitive Impairment in Patients with Breast Cancer Based on Functional Assessment and NIRS Analysis. Durán-Gómez, N., López-Jurado, CF., Nadal-Delgado, M., et al.[2023]

Neuroimaging techniques, such as MRI and PET, reveal that structural and functional changes in the brain are associated with cognitive impairments in patients undergoing treatment for non-CNS cancers, particularly those receiving chemotherapy.

There is a need for larger, multicenter studies and a standardized approach to better understand cognitive changes and develop targeted interventions, which could lead to personalized treatment strategies for cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroimaging biomarkers and cognitive function in non-CNS cancer and its treatment: current status and recommendations for future research. Saykin, AJ., de Ruiter, MB., McDonald, BC., et al.[2021]

Chemotherapy in cancer patients is associated with small to medium cognitive impairments, particularly affecting attention, processing speed, verbal memory, and executive control, as evidenced by a review of 14 studies involving adult patients.

Neuroimaging revealed significant structural changes in the brain, including reduced grey matter density and altered white matter integrity, which correlate with cognitive decline, highlighting the need for further research to understand the biological mechanisms behind these changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longitudinal assessment of chemotherapy-induced changes in brain and cognitive functioning: A systematic review. Li, M., Caeyenberghs, K.[2019]

In a study of 167 cancer patients undergoing chemotherapy, a 12-week computer-assisted cognitive rehabilitation program showed a significant improvement in perceived cognitive abilities and working memory compared to other control groups.

Patients in the computer-assisted rehabilitation group also reported better quality of life related to cognition and a reduction in depression symptoms, indicating its potential as a beneficial intervention for managing cancer-related cognitive impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive rehabilitation program to improve cognition of cancer patients treated with chemotherapy: A 3-arm randomized trial. Dos Santos, M., Hardy-Léger, I., Rigal, O., et al.[2021]

A novel computerized cognitive assessment battery, the Enformia Cogsuite, effectively identified significant cognitive deficits in breast cancer survivors (N=174) compared to age-matched controls (N=183), particularly in attention, executive function, and memory.

The Cogsuite's sensitivity to subtle cognitive dysfunctions allows for better initial diagnosis and monitoring of cognitive changes in cancer survivors, with the added benefit of remote administration to improve accessibility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel computerized neurocognitive test battery is sensitive to cancer-related cognitive deficits in survivors. Gaynor, AM., Ahsan, A., Jung, D., et al.[2022]

Breast cancer patients who underwent chemotherapy showed significant reductions in gray and white matter volume and density in key brain regions, particularly the frontal and temporal areas, compared to those who did not receive chemotherapy and healthy controls.

These structural brain changes are linked to both subjective and objective cognitive impairments, suggesting that chemotherapy may have lasting effects on brain health and cognitive function in cancer survivors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alterations in brain structure related to breast cancer and its treatment: chemotherapy and other considerations. McDonald, BC., Saykin, AJ.[2022]

A computerized cognitive training program significantly improved working memory, attention, and processing speed in 68 childhood cancer survivors, with a notable effect size indicating its efficacy.

Neuroimaging results showed that the training led to reduced activation in specific brain areas, suggesting that the cognitive improvements were associated with neuroplastic changes in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Computerized Cognitive Training for Amelioration of Cognitive Late Effects Among Childhood Cancer Survivors: A Randomized Controlled Trial. Conklin, HM., Ogg, RJ., Ashford, JM., et al.[2022]

A pilot study involving 31 off-therapy childhood cancer survivors showed that a cognitive remediation program (CRP) significantly improved attention and concentration in participants, with 21 completing the program and demonstrating better results than the comparison group.

While the CRP was effective in enhancing attentional measures, it did not lead to significant improvements in academic achievement, indicating that further research is needed to assess long-term benefits and applicability to other populations with cognitive impairments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Attentional processes and their remediation in children treated for cancer: a literature review and the development of a therapeutic approach. Butler, RW., Copeland, DR.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04230863

Neuroplasticity-Based Cognitive Remediation for ... The investigators propose to apply neuroplasticity-based computerized cognitive remediation (nCCR) to treat chemotherapy-related cognitive impairment (CRCI).

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10426301/

Use of focused computerized cognitive training (Neuroflex) to ... We proposed the use of a novel cognitive enhancement strategy called Neuroflex to target CRCI experienced by breast cancer survivors.

3. nature.com nature.com/articles/ncomms5579

Neuroplasticity-based computerized cognitive remediation ... nCCR-GD is equally as effective at reducing depressive symptoms as escitalopram but does so in 4 weeks instead of 12. In addition, nCCR-GD ...

4. journals.sagepub.com journals.sagepub.com/doi/abs/10.1177/20552076231192754

Use of focused computerized cognitive training (Neuroflex) ... Targeting cognitive control deficits with neuroplasticity-based computerized cognitive remediation in patients with geriatric major ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2950386825000231

Neural effects of a cognitive remediation intervention for ... Here we report results from a recently completed, double-blind, randomized pilot study using a digital therapeutic program, NeuroFlex, designed ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4139707/

Neuroplasticity-based computerized cognitive remediation ... Here we develop a neuroplasticity-based computerized cognitive remediation treatment (CCR-GD) to target ED in GD. Our assumption is that ...

7. withpower.com withpower.com/trial/phase-chemobrain-4-2022-1f14c

Cognitive Training for Chemobrain · Info for Participants The investigators propose to apply neuroplasticity-based computerized cognitive remediation (nCCR) to treat chemotherapy-related cognitive impairment (CRCI).