A Study Utilizing Escitalopram in Glioma Patients

Study Overview
=================
Brief Summary
-----------------
This pilot study will include grade IV glioma patients treated with SSRIs during approximately a 17 week study period. Changes in cognition and evaluation of psychosocial factors from baseline to after 17 weeks of treatment with SSRI study drug will be calculated.

Detailed Description
-----------------
As many as 85% of glioma patients experience cognitive impairment. This is not only from direct tumor involvement, but also worsens with therapy such as cranial radiation and chemotherapy, which further degrade neuronal function. Commonly, impairments in visuospatial skills and executive function are seen. There is evidence that serotonin selective reuptake inhibitors (SSRIs) such as escitalopram improve modulation and function of resting state networks, contribute to neuroplastic changes in brain regions subserving these abilities, and provide general functional support to neuronal cells. In addition to either improving cognition or preventing cognitive decline, treatment with an SSRI may also improve outcomes critical to overall survival in this vulnerable population, including functional independence, psychosocial stability, and quality of life. We hypothesize that following treatment with escitalopram patients will experience improved cognitive and mood function over time. We will also correlate changes in mood structural MRI and electrophysiological correlates of visual pathway function. The addition of escitalopram has the potential to enhance cognitive function and hence functional independence thereby improving quality of life in these patients.

Official Title
-----------------
A Pilot Study Utilizing Escitalopram to Address Cognitive Dysfunction in Glioma Patients

Conditions
-----------------
Glioma of Brain, Glioma

Intervention / Treatment
-----------------
* Drug: Escitalopram Oral Capsules


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient with pathologically proven diagnosis of Grade IV glioma Patients planning to receive chemotherapy and/or radiation for newly diagnosed disease Performance status ECOG 0-2 or equivalent Patients must be age ≥19 years Life expectancy greater than 6 months Written informed consent to participate in the study. Exclusion Criteria: Hemifield defects (as this obscures visual field necessary to participate in all tests) Inability to undergo MRI Severe renal impairment defined as GFR<30 mL/minute Screen positive for depression or anxiety Already taking an anti-depressant (SSRI or NSRI) Have problems tolerating past treatment with SSRI or NSRIs Females of childbearing potential must have a negative urine pregnancy test at the study enrollment. Female patients must be either postmenopausal, free from menses for ≥2 years, surgically sterilized, or willing to use two adequate barrier forms of contraception

Ages Eligible for Study
-----------------
Minimum Age: 19 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: grade IV glioma patients treated with SSRIs during a 17 week study period
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Escitalopram<br>This is an open-label study. Escitalopram will be administered to all participants as 10 mg capsules to be taken by mouth daily for 90 days. | Drug: Escitalopram Oral Capsules<br>* Active capsules will contain 10 mg escitalopram oxalate.<br>* Other names: Lexapro;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterize the degree of change in cognition | Changes in cognition will be measured using the NIH Toolbox neurocognitive assessments. The NIH Toolbox has excellent test / re-test reliability across composite domain scores r = .86 - .9263. It has also shown strong convergent (r = .78 - .9) and discriminant (r = .19 - .39) validities. It has been validated on groups of patients with Spinal Cord Injuries, Traumatic Brain Injury and Stroke. More recently a small group of patients diagnosed with diffuse glioma completed the NIH Toolkit Cognitive and Emotional batteries pre- and post-surgery. Results suggested good tolerance on the part of the patients and benefits of having a standardized battery that can be employed across sites. Paired t-test will be used to determine if the changes from baseline to the 17 week visit are significant. If assumptions for the paired t-test are not met, the non-parametric Wilcoxon sign rank test will be used instead. | 17 weeks | 
| Characterize the degree of change in cognition and brain function | Changes in cognition and brain function will be measured via Patient-Reported Outcome Measurement Information System (PROMIS) Neuro-QoL Item Bank v2.0 - Cognitive Function assessment completed at baseline, 12 weeks, and 17 weeks. A higher score on this measure indicate higher cognitive function. The change from baseline will be compared with the Wilcoxon sign rank test. | 17 weeks | 
| Determine the degree of change in psychosocial functions | The degree of change in psychosocial functions will be assessed via patient-reported ratings in mood and quality of life. The following assessments will be completed: PROMIS Neuro-QoL Item Bank v1.0 - Depression; PROMIS Neuro-QoL Item Bank v1.0 - Anxiety; PROMIS Neuro-QoL Item Bank v1.0 - Fatigue. Higher scores on these assessments indicate higher levels of the concept being assessed. The changes from baseline will be compared with the Wilcoxon sign rank test. | 17 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
serotonin selective reuptake inhibitor, cognition, escitalopram