This study is to determine if an oral drug called Ramipril can lower the chance of memory loss in patients with glioblastoma getting chemoradiation. Patients will take Ramipril during chemoradiation and continue until 4 months post-treatment. Memory loss will be assessed using several neurocognitive tests throughout the duration of the study.
This is a pilot study of an oral drug Ramipril to prevent cognitive decline in glioblastoma patients receiving partial brain radiation and concurrent and adjuvant temozolomide . Ramipril will be titrated to the highest tolerable dose during chemoradiation (2.5-5 mg). Once this dose is determined, the patient will continue at this dose for 4 months after the completion of chemoradiation. Patients will be followed until 5 months post chemoradiation for compliance, toxicity, cognitive decline and participant reported outcomes (PRO).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
SUPPORTIVE_CARE
Masking
NONE
Enrollment
75
2.5 - 5 mg oral, 1x daily for 22 weeks
Change from Baseline Neurocognitive Function at 10 weeks - Hopkins Verbal Learning Test-Revised (HVLT-R)
HVLT-R measures verbal learning and memory. It consists of a 12-item word list which is read to subjects on three successive learning trials. Free recall scores are recorded for each learning trial. Scores for immediate recall (total of three trials), delayed recall (total number of words recalled after 20 minutes), and recognition (total number of words correctly identified) will be the variables derived from the HVLT-R.
Time frame: Baseline,10 weeks
Change from Baseline Neurocognitive Function at 10 weeks - Trail Making Test Part A and B (TMT A & B)
Part A of the TMT measures attention and visual motor skills and processing speed and requires subjects to connect 25 numbered circles in the proper sequence (1-2-3-…) as quickly as possible. TMT-B is similar except subjects are required to connect dots in an alternating numerical and alphabetical sequence (1-A-2-B-…). TMT-B with its added complexity and set shifting requirements is a widely used measure of executive function. The score for TMT-A and TMT-B is the total time in seconds required to complete the task. Scores can also be generated for number of errors and number of circles correctly connected.
Time frame: Baseline,10 weeks
Change from Baseline Neurocognitive Function at 10 weeks - Controlled Oral Word Association Test (COWA)
The COWA measures speed of mental processing, verbal fluency, and executive function. Subjects are asked to name as many words as possible all beginning with a specified letter. A total of three trials are administered, each with a different letter (F-A-S). The score on the COWA is the total number of words named across the three trials minus repetitions.
Time frame: Baseline,10 weeks
Efficacy of Ramipril of Neurocognitive Function at Baseline - Shipley Institute of Living Scale-Version 2 Vocabulary
Provides an assessment of premorbid intellectual functioning comparable to a verbal IQ and thus is a proxy for cognitive reserve. This vocabulary test requires respondents to read a target word and select one of four words that most closely means the same thing. Score is total correct of 40 items and will be used in conjunction with the other neurocognitive results.
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Time frame: Baseline
Retention Rate at 10 weeks
Measured by the percent of patients who took 75% of the Ramipril doses and completed the neurocognitive battery of tests
Time frame: 10 weeks
Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20)
A 50-item questionnaire with a 20-item brain cancer specific section, used to assess the physical and psychosocial functioning and symptom experience. All of the scales and single-item measures range in score from 0 to 100 with standardization.
Time frame: Baseline, 6 weeks, 10 weeks, 22 weeks
Estimate Time of Neurocognitive Decline- HVLT-R
Measured by the first significant decline of the HVLT-R.
Time frame: Baseline - 22 weeks
Estimate Time of Neurocognitive Decline- TMT A & B
Measured by the first significant decline of the TMT A \& B
Time frame: Baseline - 22 weeks
Estimate Time of Neurocognitive Decline- COWA
Measured by the first significant decline of the COWA
Time frame: Baseline - 22 weeks
Determine Presence of Apolipoprotein Epsilon (ApoE)
Measured by quantitative polymerase chain reaction (PCR) using patient serum via a blood test
Time frame: Baseline
Efficacy of neurocognitive function in surviving patients- HVLT-R
Comparison of HVLT-R results between groups at study end.
Time frame: 22 weeks
Efficacy of neurocognitive function in surviving patients- TMT A & B
Comparison of TMT A \& B results between groups at study end.
Time frame: 22 weeks
Efficacy of neurocognitive function in surviving patients- COWA
Comparison of COWA results between groups at study end.
Time frame: 22 weeks
Efficacy of neurocognitive function in surviving patients- EORTCQLQ30/BN20
Comparison of EORTCQLQ30/BN20 results between groups at study end.
Time frame: 22 weeks