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

15 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a brain stimulation technique that uses magnetic pulses to improve brain function. It targets patients who have cognitive problems due to chemotherapy. The goal is to see if this treatment can help with higher-order thinking skills by changing brain activity. This noninvasive technique has been used in various therapeutic contexts.

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 data supports the effectiveness of the treatment Accelerated repetitive intermittent theta-burst transcranial stimulation (iTBS) for chemotherapy-induced cognitive impairment?

Research shows that iTBS, a type of brain stimulation, has been effective in reducing symptoms of depression and improving abstinence rates in smokers, suggesting it may help with cognitive issues by positively affecting brain function. ^{1 2 3 4 5}

Is intermittent theta-burst stimulation (iTBS) safe for humans?

Intermittent theta-burst stimulation (iTBS) has been studied in healthy volunteers and is generally considered safe, with no significant adverse effects reported in the studies. It has been used to influence brain activity related to emotion processing and working memory, suggesting it is well-tolerated in humans. ^{4 5 6 7 8}

How does the treatment for chemotherapy-induced cognitive impairment differ from other treatments?

Accelerated repetitive intermittent theta-burst transcranial stimulation (iTBS) is unique because it is a noninvasive brain stimulation technique that mimics the brain's natural firing patterns, potentially leading to greater cognitive improvements compared to standard methods. Unlike traditional treatments, iTBS is applied directly to the brain's prefrontal cortex, which may enhance cognitive performance more effectively. ^{2 3 5 7 9}

Research Team

Sneha Phadke, DO

Principal Investigator

University of Iowa Hospitals & Clinics

Eligibility Criteria

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

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

Treatment Details

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'.

Participant Groups

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+

Findings from Research

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Can intermittent theta burst stimulation as add-on to psychotherapy improve nicotine abstinence? Results from a pilot study. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

The Effects of Bilateral Theta-burst Stimulation on Executive Functions and Affective Symptoms in Major Depressive Disorder. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Accelerated intermittent theta burst stimulation in major depression induces decreases in modularity: A connectome analysis. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Intermittent theta burst stimulation over ipsilesional primary motor cortex of subacute ischemic stroke patients: a pilot study. [2022]

5. Ireland pubmed.ncbi.nlm.nih.gov

Reproducibility and sources of interindividual variability in the responsiveness to prefrontal continuous theta burst stimulation (cTBS). [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Influence of theta-burst transcranial magnetic stimulation over the dorsolateral prefrontal cortex on emotion processing in healthy volunteers. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Enhancement of Working Memory and Task-Related Oscillatory Activity Following Intermittent Theta Burst Stimulation in Healthy Controls. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Impact of different intensities of intermittent theta burst stimulation on the cortical properties during TMS-EEG and working memory performance. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Improved Cognitive Promotion through Accelerated Magnetic Stimulation. [2022]