Escitalopram for Brain Tumor

Overseen By IIT Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Nebraska

Must be taking: SSRIs

Must not be taking: Antidepressants

Disqualifiers: Severe renal impairment, Depression, 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: 29

Duration: 12 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests escitalopram, an SSRI commonly used as an antidepressant, to determine its effectiveness in addressing cognitive issues in individuals with grade IV glioma. Many patients with this cancer experience problems with thinking and memory due to the tumor and treatments like radiation and chemotherapy. The trial aims to discover whether escitalopram can improve these cognitive issues and enhance overall quality of life. It seeks participants recently diagnosed with grade IV glioma who are about to begin chemotherapy or radiation. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that participants are not already taking an anti-depressant (SSRI or NSRI), so you may need to stop these medications before joining.

Is there any evidence suggesting that escitalopram is likely to be safe for humans?

Research shows that escitalopram, a type of antidepressant, is usually well-tolerated by patients. The FDA has approved it for treating depression and anxiety, indicating it has been tested and found safe for those conditions.

Regarding brain tumors, some studies suggest that escitalopram might offer potential benefits against cancer. However, other research presents mixed results. For example, escitalopram may help in certain lab settings but could also increase tumor growth in some animal studies.

Overall, escitalopram is considered safe for human use based on its approval for other conditions. However, its specific effects on brain tumor patients remain under study. Participants should discuss any concerns with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for brain tumors, which often involve surgery, radiation, and chemotherapy, escitalopram is a medication typically used for depression. Researchers are excited about escitalopram because it might offer a new way to help brain tumor patients by potentially affecting the brain's chemistry in a beneficial way. This treatment stands out because it is taken as a daily oral capsule, which could make it much easier and less invasive for patients compared to traditional options. Additionally, if escitalopram proves effective, it could provide a less toxic alternative or complement to existing therapies, focusing on quality of life.

What evidence suggests that escitalopram might be an effective treatment for cognitive impairment in glioma?

Research has shown that escitalopram, a common antidepressant, might help with aggressive brain tumors. Some studies suggest it can fight tumor cells and prevent their spread. It may also improve thinking and memory in patients with brain tumors, enhancing their quality of life. In this trial, all participants will receive escitalopram to further investigate its potential benefits. Although more research is needed, these findings offer hope that escitalopram could address cognitive problems in glioma patients. ^{1 5 6 7 8}

Who Is on the Research Team?

Nicole A Shonka, MD

Principal Investigator

University of Nebraska

Are You a Good Fit for This Trial?

This study is for adults over 19 with a specific brain tumor called Grade IV glioma, who are about to start or are currently receiving chemo and/or radiation. They should be able to perform daily activities (ECOG 0-2), have a life expectancy over 6 months, and not be pregnant. Those with severe kidney issues, depression or anxiety, visual field defects, or intolerance to similar medications cannot join.

Inclusion Criteria

Written informed consent to participate in the study

Life expectancy greater than 6 months

I am about to start chemotherapy or radiation for my newly diagnosed condition.

Exclusion Criteria

I am currently on an SSRI or SNRI antidepressant.

I am a woman who is postmenopausal, had no periods for 2+ years, am sterilized, or will use two forms of birth control.

I had side effects from SSRI or SNRI medications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive escitalopram 10 mg daily for 90 days to address cognitive dysfunction

12 weeks

Baseline, 12 weeks, and 17 weeks assessments

Follow-up

Participants are monitored for changes in cognition and psychosocial functions after treatment

5 weeks

17 weeks assessment

What Are the Treatments Tested in This Trial?

Interventions

• Escitalopram

Trial Overview

The trial tests Escitalopram Oral Capsules on patients with grade IV glioma over approximately 17 weeks. It aims to see how the drug affects cognition and psychosocial factors in these patients during their treatment period.

How Is the Trial Designed?

Group I: Escitalopram Experimental Treatment 1 Intervention

In this open-label study, Escitalopram will be administered to all participants as 10 mg capsules to be taken by mouth daily for 90 days.

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

Approved in United States as Lexapro for:

• Major depressive disorder
• Generalized anxiety disorder

Approved in European Union as Cipralex for:

• Major depressive episodes
• Generalized anxiety disorder
• Social anxiety disorder
• Panic disorder with or without agoraphobia
• Obsessive-compulsive disorder

Approved in Canada as Cipralex for:

• Major depressive disorder
• Generalized anxiety disorder
• Social anxiety disorder

Who Is Running the Clinical Trial?

University of Nebraska

Lead Sponsor

Trials

563

Recruited

1,147,000+

Nicole Shonka

Lead Sponsor

Trials

1

Recruited

20+

Published Research Related to This Trial

In a study of 497 glioblastoma patients, the use of selective serotonin reuptake inhibitors (SSRIs) did not show a significant association with improved overall survival, indicating that SSRIs may not enhance survival outcomes in these patients.

Despite the lack of survival benefit from SSRIs alone, further research is needed to explore their potential effects when combined with other treatments, such as immunotherapies, for glioblastoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective survival analysis of Glioblastoma patients treated with selective serotonin reuptake inhibitors. Otto-Meyer, S., DeFaccio, R., Dussold, C., et al.[2021]

Citalopram was well tolerated in a small open-label study of four pediatric oncology patients with depression, suggesting it may be a safe option for this vulnerable population.

Preliminary data indicate that citalopram could be effective as an antidepressant in pediatric oncology patients, offering potential advantages over fluoxetine, particularly in terms of drug interactions and half-life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Citalopram to treat depression in pediatric oncology. DeJong, M., Fombonne, E.[2022]

In a study of 32 pediatric cancer patients aged 2-21, both SSRIs and mirtazapine were found to be effective in improving psychiatric symptoms, with 84% of patients showing improvement after treatment.

The antidepressants were well tolerated, with only mild adverse events reported, suggesting they are safe options for managing depression and anxiety in children and adolescents with cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychopharmacology in the Pediatric Oncology and Bone Marrow Transplant Units: Antidepressant Treatment. Lavan, O., Peled, O., Avishai-Neumann, M., et al.[2022]

In a 12-week study involving 79 breast cancer outpatients, escitalopram significantly reduced depression symptoms and improved quality of life, with noticeable improvements starting as early as one week into treatment.

By the end of the study, 45.1% of participants showed a significant response to treatment (at least a 50% decrease in depression scores), and 30.6% achieved remission, indicating escitalopram's efficacy in managing depression in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid improvement of depression and quality of life with escitalopram treatment in outpatients with breast cancer: a 12-week, open-label prospective trial. Park, HY., Lee, BJ., Kim, JH., et al.[2013]

In a study of 283 patients with brain tumors, 15.4% of those treated with antiepileptic drugs (AEDs) experienced treatment emergent psychiatric adverse events (TE-PAEs), particularly associated with tumors in the frontal lobe and the use of levetiracetam.

The findings suggest that using an alternative AED to levetiracetam may help reduce the risk of developing psychiatric symptoms in patients with frontal lobe tumors, highlighting the importance of considering drug choice in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain tumor location influences the onset of acute psychiatric adverse events of levetiracetam therapy: an observational study. Belcastro, V., Pisani, LR., Bellocchi, S., et al.[2018]

Recent research has shown that certain psychiatric drugs, including valproic acid, fluoxetine, escitalopram, and aripiprazole, may have potential in treating malignant brain tumors, highlighting their anticancer properties through various laboratory and clinical studies.

The review emphasizes the need to address limitations in repurposing these medications for brain cancer treatment, particularly for vulnerable populations like children and pregnant women, while suggesting future research directions to improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surprising Anticancer Activities of Psychiatric Medications: Old Drugs Offer New Hope for Patients With Brain Cancer. Zhuo, C., Xun, Z., Hou, W., et al.[2020]

In a 24-week study involving 357 patients with moderate to severe major depressive disorder, escitalopram was found to be at least as effective as citalopram, with statistically significant superiority in improving overall severity of depression by Week 24.

Both medications were safe and well tolerated, but escitalopram had fewer patient withdrawals compared to citalopram, highlighting its potential for better long-term adherence in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, 24-week study of escitalopram (10 mg/day) versus citalopram (20 mg/day) in primary care patients with major depressive disorder. Colonna, L., Andersen, HF., Reines, EH.[2022]

In a pooled analysis of over 1700 glioblastoma patients, antidepressant use at baseline or the start of maintenance therapy did not significantly affect progression-free survival (PFS) or overall survival (OS), suggesting limited efficacy in improving survival outcomes.

However, patients using antidepressants at the start of maintenance cycle 4 experienced significantly worse overall survival, indicating a potential negative impact that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of antidepressant drug use with outcome of patients with glioblastoma. Seliger, C., Oppong, FB., Lefranc, F., et al.[2023]

Imipramine and citalopram, both used for treating depression, may offer potential benefits for patients with malignant glioma, suggesting a need for large epidemiological studies to explore their efficacy in this context.

Recent studies have shown that digoxin, a heart failure medication, can provide unexpected benefits in prostate cancer treatment, highlighting the importance of investigating the effects of existing drugs in new patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Voltage-dependent K+ channels as oncotargets in malignant gliomas. Lefranc, F., Pouleau, HB., Rynkowski, M., et al.[2021]

Psychotropic drugs, such as antipsychotics and antidepressants, can cross the blood-brain barrier and may inhibit the growth of glioma by affecting key signaling pathways involved in cell proliferation and apoptosis.

These drugs have shown potential as anticancer agents in preclinical and clinical studies, suggesting they can be repurposed for glioma treatment while maintaining their established safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug repositioning: Using psychotropic drugs for the treatment of glioma. You, F., Zhang, C., Liu, X., et al.[2022]

Valproate (VPA) shows promise in treating glioblastoma multiforme by inhibiting tumor growth through mechanisms such as histone deacetylase inhibition, which leads to gene transcription changes that promote cell differentiation and reduce invasion.

VPA may enhance the effectiveness of traditional treatments like chemotherapy and radiation by inhibiting DNA repair, suggesting that combining VPA with these therapies could be a beneficial strategy for glioblastoma patients, warranting further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Valproic acid for the treatment of malignant gliomas: review of the preclinical rationale and published clinical results. Berendsen, S., Broekman, M., Seute, T., et al.[2013]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5783874/

Escitalopram oxalate induces apoptosis in U‐87MG cells and ...

The experimental results revealed that escitalopram oxalate significantly inhibits the proliferation and invasive ability of U‐87MG cells.

2.

sciencedirect.com

sciencedirect.com/science/article/pii/S1476558625000612

Escitalopram facilitates tumor growth and metastasis in ...

By day 30, tumors in the escitalopram group had increased 22 % from baseline, whereas control tumors exhibited a 35 % reduction. (C) Representative BLI images ...

3.

braintumourresearch.org

braintumourresearch.org/blogs/latest-news/antidepressant-found-to-be-unexpectedly-effective-against-brain-tumours?srsltid=AfmBOop5fayedwgeitvQIOLIh0-gaY--l8Q_Nq5ZjoQgFiyNwNAN0LbU

Antidepressant found to be “unexpectedly effective” against ...

A cheap and widely available antidepressant has shown to be “unexpectedly effective” in treating aggressive brain tumours, a new study reveals.

4.

withpower.com

withpower.com/trial/phase-3-glioma-2-2019-c12f6

Escitalopram for Brain Tumor

Some research suggests that psychiatric drugs like escitalopram may have potential anticancer properties, showing promise in brain tumor treatment strategies.

5.

centerwatch.com

centerwatch.com/clinical-trials/listings/NCT03728673/a-study-utilizing-escitalopram-in-glioma-patients

A Study Utilizing Escitalopram in Glioma Patients

This pilot study will evaluate the effectiveness of the selective serotonin reuptake inhibitor (SSRI) escitalopram for treating cognitive ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12152346/

Escitalopram facilitates tumor growth and metastasis in ...

Escitalopram increased primary tumor growth 1.4-2.2-fold in multiple rodent models. Metastases were enhanced by 1.6-2.3-fold in mammary and colon cancers.

7.

sciencedirect.com

sciencedirect.com/science/article/pii/S2666354619300250

A retrospective survival analysis of Glioblastoma patients ...

SSRI use was not associated with improved overall survival in GBM patients. Analysis included fluoxetine, citalopram, escitalopram, sertraline, paroxetine, ...

8.

onlinelibrary.wiley.com

onlinelibrary.wiley.com/doi/full/10.1002/ijc.34344

Association of antidepressant drug use with outcome of ...

We found no significant association between the use of antidepressants at baseline or at the start of maintenance therapy and PFS or OS.