Neuromodulation for Chemotherapy-Induced Cognitive Impairment

Overseen By Kanchna Ramchandran, MS, PHD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Sneha Phadke

Must not be taking: Benzodiazepines

Disqualifiers: Metastatic cancer, Brain tumor, Seizures, others

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

Compensation: Varies

Number of Visits: 8

Duration: 1.5 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for "chemo-brain," which includes memory loss and difficulty concentrating after chemotherapy. The treatment uses a special brain stimulation called accelerated repetitive intermittent theta-burst transcranial stimulation (iTBS). Participants may receive either the actual treatment or a placebo. This trial suits individuals who have completed cancer treatment, experienced "chemo-brain" symptoms, and can attend study visits. As an unphased trial, it offers a unique opportunity to contribute to groundbreaking research that could enhance cognitive recovery after chemotherapy.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, if you are receiving maintenance systemic therapy for cancer, other than endocrine therapy, you may not be eligible to participate.

What prior data suggests that this neuro-modulation technique is safe for alleviating chemotherapy-induced cognitive deficits?

Research has shown that accelerated repetitive intermittent theta-burst transcranial stimulation (iTBS) is generally safe. One study found that brain stimulation levels were safe and effective for all participants, indicating the treatment was well-tolerated without harmful effects at the tested levels. Another study confirmed iTBS as a safe and practical method for non-invasive brain stimulation, further supporting its safety. Overall, iTBS appears to be a promising option with a good safety record in studies so far. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for chemotherapy-induced cognitive impairment focus on managing symptoms through medications or cognitive rehabilitation strategies. However, the accelerated repetitive intermittent theta-burst transcranial stimulation (iTBS) is unique because it uses a non-invasive brain stimulation technique that can potentially enhance cognitive function by directly modulating neural activity. Researchers are excited about iTBS because it targets specific brain areas associated with cognitive processes, offering a more precise approach compared to general cognitive symptom management. Additionally, iTBS could provide faster results and be more convenient, with fewer side effects than traditional medication-based therapies.

What evidence suggests that accelerated repetitive intermittent theta-burst transcranial stimulation (iTBS) is effective for chemotherapy-induced cognitive impairment?

Research has shown that accelerated repetitive intermittent theta-burst transcranial stimulation (iTBS) might improve thinking and memory. One study found that people who received iTBS had better cognitive function after six weeks. Other research suggests that this treatment could enhance brain connectivity, potentially boosting thinking and memory skills. Additional studies have demonstrated that iTBS can aid those with mild cognitive impairment, similar to the cognitive issues some face after chemotherapy. In this trial, participants will receive either iTBS or a sham version to evaluate its effectiveness for chemotherapy-induced cognitive impairment. Overall, promising evidence suggests that iTBS could help with the cognitive challenges experienced after chemotherapy. ^{6 7 8 9 10}

Who Is on the Research Team?

Sneha Phadke, DO

Principal Investigator

University of Iowa Hospitals & Clinics

Are You a Good Fit for This Trial?

This trial is for adults who've had non-metastatic cancer, finished curative therapy including chemotherapy at least a month ago, and are experiencing 'chemo-brain' symptoms like memory issues or trouble concentrating. They must be able to consent and follow study procedures but can't join if they're pregnant, over 250 lbs., need benzodiazepines for MRI anxiety, have metal implants incompatible with MRI/TMS, history of seizures/epilepsy/concussions, active substance use (except tobacco), brain metastasis/tumor history or ongoing metastatic disease.

Inclusion Criteria

Ability to sign informed consent and comply with study procedures

I had cancer that did not spread and have completed all treatments aimed at curing it.

I was 18 or older when diagnosed with cancer and received chemotherapy.

Exclusion Criteria

Patients with chest wall tissue expanders or other retained 7 Tesla MRI-incompatible metal. Any other specific contraindication to TMS or MRI not already listed above, including: (a) any implanted device in the head, neck or upper body (e.g. cochlear implant, cranial or other electrodes, pacemaker or defibrillator, medication pump, stent, aneurysm clip, etc.) (b) personal history of seizures or epilepsy, personal history of multiple concussions or unexplained loss of consciousness. This will be determined by physician judgement

Patients who cannot produce or request adequate medical record documentation to ensure they meet inclusion and exclusion criteria

Women who are currently pregnant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive accelerated repetitive intermittent theta-burst transcranial stimulation (iTBS) or sham stimulation over 8 visits

1.5 months

8 visits (in-person)

Follow-up

Participants are monitored for changes in brain metabolite concentrations and executive cognitive function

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Accelerated repetitive intermittent theta-burst transcranial stimulation (iTBS)

Trial Overview The trial tests accelerated repetitive intermittent theta-burst transcranial stimulation (iTBS) as a potential treatment to improve cognitive functions affected by chemotherapy. It focuses on executive functions such as decision-making and problem-solving in those reporting 'chemo-brain'.

How Is the Trial Designed?

Group I: Accelerated repetitive intermittent theta-burst transcranial stimulation (iTBS) or sham Experimental Treatment 1 Intervention

Patients will participate in the prospective longitudinal research protocol over a period of 1.5 months. Treatment will include 8 visits of either accelerated repetitive intermittent theta-burst transcranial stimulation (iTBS) or iTBS sham stimulation. Patients will be informed that iTBS sham stimulations will be part of the protocol (but will be blind to when treatment/sham will be administered).

Who Is Running the Clinical Trial?

Sneha Phadke

Lead Sponsor

Trials

1

Recruited

20+

Kanchna Ramchandran

Lead Sponsor

Trials

1

Recruited

20+

American Cancer Society-Holden Comprehensive Cancer Society

Collaborator

Trials

1

Recruited

20+

Fraternal Order of Eagles (Iowa)

Collaborator

Trials

1

Recruited

20+

Published Research Related to This Trial

In a study involving 12 subacute stroke patients, prolonged transcranial magnetic stimulation (iTBS1200) was found to be safe and well-tolerated, with no significant adverse effects reported.

Patients receiving iTBS1200 showed measurable improvements in stroke severity and upper extremity function shortly after treatment and at 60 days post-stroke, suggesting potential benefits that warrant further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent theta burst stimulation over ipsilesional primary motor cortex of subacute ischemic stroke patients: a pilot study. Hsu, YF., Huang, YZ., Lin, YY., et al.[2022]

In a study involving 19 healthy participants, intermittent theta burst stimulation (iTBS) to the left dorsolateral prefrontal cortex significantly improved working memory performance for up to 40 minutes compared to sham stimulation.

The cognitive improvements were linked to increased synchronization of theta waves and enhanced gamma band power in the brain, suggesting that specialized stimulation techniques may offer more effective neuromodulation for cognitive enhancement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancement of Working Memory and Task-Related Oscillatory Activity Following Intermittent Theta Burst Stimulation in Healthy Controls. Hoy, KE., Bailey, N., Michael, M., et al.[2018]

In a study involving 50 patients with treatment-resistant depression (TRD), accelerated intermittent theta burst stimulation (aiTBS) significantly reduced depression symptoms over time, indicating its potential efficacy as a noninvasive treatment option.

The treatment was associated with changes in brain network organization, specifically a reduction in modularity of structural networks, suggesting that aiTBS may promote beneficial neuroplasticity effects in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated intermittent theta burst stimulation in major depression induces decreases in modularity: A connectome analysis. Caeyenberghs, K., Duprat, R., Leemans, A., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12465570/

Effects of intermittent theta-burst stimulation on cognition ... Significant cognitive improvements were observed at week 6 in the iTBS group, indicating delayed cognitive enhancement, though no immediate ...

2. jnnp.bmj.com jnnp.bmj.com/content/95/11/1036

A phase I trial of accelerated intermittent theta burst rTMS for ... Results Retention was high (95%) and there were no adverse neuroradiological, neuropsychiatric, or neurocognitive effects of treatment. Participants reported ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X25000932

Accelerated iTBS-Induced changes in resting-state ... Cognitive improvement following a-iTBS in MCI may be attributable to local and network-level reconfigurations in functional connectivity.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11483208/

A phase I trial of accelerated intermittent theta burst rTMS ... Background: Emerging evidence suggests that repetitive transcranial magnetic stimulation (rTMS) enhances cognition in mild cognitive impairment (MCI).

5. trialsjournal.biomedcentral.com trialsjournal.biomedcentral.com/articles/10.1186/s13063-024-08606-8

The cerebral and cognitive changes after intermittent theta ... We expect that patients who received iTBS treatment will display significantly larger changes in functional BOLD response, with significantly ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40658276/

Effects of accelerated intermittent theta-burst stimulation ... These findings suggest that the combined intervention can effectively promote cognitive performance and brain function in aMCI patients.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38719432/

A phase I trial of accelerated intermittent theta burst rTMS for ... Electric field modeling data suggest that all participants received safe and therapeutic cortical stimulation intensities. We observed a ...

8. withpower.com withpower.com/trial/phase-cognitive-dysfunction-8-2023-cc0ad

Accelerated iTBS for Mild Cognitive Impairment The goal of this phase II study is to establish the dose-response curves of a safe and clinically feasible non-invasive brain stimulation technique ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT01315587

Repetitive Transcranial Magnetic Stimulation and ... The aim of this study is to investigate the effect of repetitive TMS and theta burst in reduction of negative symptoms and remission of cognitive functioning in ...

10. mdpi.com mdpi.com/1424-8220/23/19/8017

Transcranial Magnetic Stimulation for the Treatment of ... This pilot feasibility study aimed to evaluate the effects of transcranial magnetic stimulation (TMS) on chemotherapy-related cognitive impairment (CRCI).