Trial Outcomes & Findings for Testing Ramipril to Prevent Memory Loss in People With Glioblastoma (NCT NCT03475186)

Last Updated: 2026-03-13

Results Overview

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. A raw score (0-36) for part A Total Recall is calculated as the total number of words correctly recalled amongst the three trials. Test scores are presented as standardized z scores (mean=0, sd=1) with infinite range. Higher standardized scores indicate better neurocognitive function. Change in standardized scores are compared with results from the control arm of RTOG0825 (NCT00884741).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

75 participants

Primary outcome timeframe

Baseline,10 weeks

Results posted on

2026-03-13

Participant Flow

Participant milestones

Participant milestones
Measure	Ramipril Ramipril will be taken once daily by mouth. It will be titrated during the first 3 weeks of chemoradiation to the highest tolerable dose (2.5-5 mg). This dose will be taken each day until 4 months post-chemoradiation treatment (22 weeks).
During Radiotherapy STARTED	75
During Radiotherapy COMPLETED	61
During Radiotherapy NOT COMPLETED	14
Primary Endpoint: 1-Month Post-RT STARTED	61
Primary Endpoint: 1-Month Post-RT COMPLETED	56
Primary Endpoint: 1-Month Post-RT NOT COMPLETED	5
4-Months Post-RT STARTED	56
4-Months Post-RT COMPLETED	46
4-Months Post-RT NOT COMPLETED	10
Follow-Up: 5-Months Post-RT STARTED	46
Follow-Up: 5-Months Post-RT COMPLETED	43
Follow-Up: 5-Months Post-RT NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Ramipril Ramipril will be taken once daily by mouth. It will be titrated during the first 3 weeks of chemoradiation to the highest tolerable dose (2.5-5 mg). This dose will be taken each day until 4 months post-chemoradiation treatment (22 weeks).
During Radiotherapy Physician Decision	3
During Radiotherapy Creatinine increased	2
During Radiotherapy Lost to Follow-up	1
During Radiotherapy Too sick or ill	1
During Radiotherapy Hospice	1
During Radiotherapy Did not like the study assessments/questionnaires	1
During Radiotherapy Did not like the intervention	1
During Radiotherapy Overwhelmed	1
During Radiotherapy Non-compliance	1
During Radiotherapy Other	2
Primary Endpoint: 1-Month Post-RT Hospice	3
Primary Endpoint: 1-Month Post-RT Disease progression	1
Primary Endpoint: 1-Month Post-RT Other	1
4-Months Post-RT Disease progression	3
4-Months Post-RT Too sick or ill	3
4-Months Post-RT Physician Decision	2
4-Months Post-RT Hospice	2
Follow-Up: 5-Months Post-RT Death	2
Follow-Up: 5-Months Post-RT Overwhelmed	1

Baseline Characteristics

Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ramipril n=75 Participants Ramipril will be taken once daily by mouth. It will be titrated during the first 3 weeks of chemoradiation to the highest tolerable dose (2.5-5 mg). This dose will be taken each day until 4 months post-chemoradiation treatment (22 weeks).
Age, Continuous	63 years n=75 Participants
Sex: Female, Male Female	26 Participants n=75 Participants
Sex: Female, Male Male	49 Participants n=75 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=75 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	72 Participants n=75 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=75 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=75 Participants
Race (NIH/OMB) Asian	0 Participants n=75 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=75 Participants
Race (NIH/OMB) Black or African American	5 Participants n=75 Participants
Race (NIH/OMB) White	67 Participants n=75 Participants
Race (NIH/OMB) More than one race	1 Participants n=75 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=75 Participants
Baseline Symptom Burden Normal, no complaints, no symptoms of disease	18 Participants n=73 Participants • Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures
Baseline Symptom Burden Able to carry on normal activity, minor symptoms of disease	15 Participants n=73 Participants • Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures
Baseline Symptom Burden Normal activity with effort, some symptoms of disease	14 Participants n=73 Participants • Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures
Baseline Symptom Burden Require occasional assistance but able to care for most of personal needs	13 Participants n=73 Participants • Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures
Baseline Symptom Burden Care for self, unable to carry on normal activity or to do active work	6 Participants n=73 Participants • Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures
Baseline Symptom Burden Require considerable assistance for personal care	4 Participants n=73 Participants • Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures
Baseline Symptom Burden Unknown/No information	3 Participants n=73 Participants • Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures
Number of times fallen in the last 6 months	0.76 count STANDARD_DEVIATION 1.67 • n=70 Participants • Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures. An additional 3 participants reported no information.
Medical history Hypertension requiring medication	27 Participants n=73 Participants • Measure Analysis Population Description: Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures.
Medical history Diabetes	15 Participants n=73 Participants • Measure Analysis Population Description: Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures.
Medical history Liver disease	2 Participants n=73 Participants • Measure Analysis Population Description: Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures.
Medical history Hemiplegia	2 Participants n=73 Participants • Measure Analysis Population Description: Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures.
Medical history Congestive heart failure	1 Participants n=73 Participants • Measure Analysis Population Description: Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures.
Medical history Cerebrovascular disease	1 Participants n=73 Participants • Measure Analysis Population Description: Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures.
Medical history Chronic pulmonary disease	1 Participants n=73 Participants • Measure Analysis Population Description: Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures.
Medical history Other cancer	9 Participants n=73 Participants • Measure Analysis Population Description: Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures.
Medical history Other medical conditions	38 Participants n=73 Participants • Measure Analysis Population Description: Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures.
Medical history None	17 Participants n=73 Participants • Measure Analysis Population Description: Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures.
Medical history Myocardial infarction	0 Participants n=73 Participants • Measure Analysis Population Description: Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures.
Medical history Peripheral vascular disease	0 Participants n=73 Participants • Measure Analysis Population Description: Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures.
Medical history Connective tissue disease	0 Participants n=73 Participants • Measure Analysis Population Description: Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures.
Medical history Peptic ulcer disease	0 Participants n=73 Participants • Measure Analysis Population Description: Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures.
Medical history HIV/AIDS	0 Participants n=73 Participants • Measure Analysis Population Description: Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures.
Site of Lesion Frontal	20 Participants n=73 Participants • Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures.
Site of Lesion Temporal	22 Participants n=73 Participants • Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures.
Site of Lesion Parietal	11 Participants n=73 Participants • Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures.
Site of Lesion Occipital	3 Participants n=73 Participants • Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures.
Site of Lesion Basal ganglia	2 Participants n=73 Participants • Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures.
Site of Lesion Multiple	10 Participants n=73 Participants • Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures.
Site of Lesion None	5 Participants n=73 Participants • Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures.
ECOG performance status 0	21 Participants n=73 Participants • Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures.
ECOG performance status 1	47 Participants n=73 Participants • Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures.
ECOG performance status 2	5 Participants n=73 Participants • Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures.
Tumor laterality Right	32 Participants n=73 Participants • Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures.
Tumor laterality Left	35 Participants n=73 Participants • Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures.
Tumor laterality Missing	6 Participants n=73 Participants • Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures.
IDH mutation status (IDH1) Wild type	42 Participants n=73 Participants • Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures.
IDH mutation status (IDH1) Unknown	31 Participants n=73 Participants • Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures.
IDH mutation status (IDH2) Wild type	30 Participants n=73 Participants • Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures.
IDH mutation status (IDH2) Unknown	43 Participants n=73 Participants • Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures.
No measurable disease	37 Participants n=73 Participants • Total number of participants consented was 75, but 2 participants withdrew before completing all baseline measures.

PRIMARY outcome

Timeframe: Baseline,10 weeks

Population: Analyses for the Ramipril arm were conducted as intent to treat. Analyses for both arms include patients with available data for the neurocognitive tests at both timepoints.

Outcome measures

Outcome measures
Measure	Ramipril n=61 Participants Ramipril will be taken once daily by mouth. It will be titrated during the first 3 weeks of chemoradiation to the highest tolerable dose (2.5-5 mg). This dose will be taken each day until 4 months post-chemoradiation treatment (22 weeks).	RTOG 0825 Control Arm n=160 Participants RTOG 0825 was a prospective, randomized phase III trial in newly diagnosed patients with glioblastoma comparing standard radiation and temozolomide therapy with and without bevacizumab. This arm consists of patients with GBM receiving radiation with concurrent and adjuvant temozolomide per the RTOG 0825 standard arm.
Change From Baseline Neurocognitive Function at 10 Weeks - Hopkins Verbal Learning Test-Revised (HVLT-R) Total Recall Standardized Score	0.09 Change in standardized score Interval -0.73 to 0.47	-0.40 Change in standardized score Interval -1.1 to 0.5

PRIMARY outcome

Timeframe: Baseline,10 weeks

Population: Analyses for the Ramipril arm were conducted as intent to treat. Analyses for both arms include patients with available data for the neurocognitive tests at both timepoints.

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. A raw score (0-12) for part B Delayed Recall is calculated as the number of words correctly recalled. Test scores are presented as standardized z scores (mean=0, sd=1) with infinite range. Higher standardized scores indicate better neurocognitive function. Change in standardized scores are compared with results from the control arm of RTOG0825 (NCT00884741).

Outcome measures

Outcome measures
Measure	Ramipril n=61 Participants Ramipril will be taken once daily by mouth. It will be titrated during the first 3 weeks of chemoradiation to the highest tolerable dose (2.5-5 mg). This dose will be taken each day until 4 months post-chemoradiation treatment (22 weeks).	RTOG 0825 Control Arm n=160 Participants RTOG 0825 was a prospective, randomized phase III trial in newly diagnosed patients with glioblastoma comparing standard radiation and temozolomide therapy with and without bevacizumab. This arm consists of patients with GBM receiving radiation with concurrent and adjuvant temozolomide per the RTOG 0825 standard arm.
Change From Baseline Neurocognitive Function at 10 Weeks - Hopkins Verbal Learning Test-Revised (HVLT-R) Delayed Recall Standardized Score	0.00 Change in standardized score Interval -0.71 to 0.59	-0.60 Change in standardized score Interval -1.6 to 0.0

PRIMARY outcome

Timeframe: Baseline,10 weeks

Population: Analyses for the Ramipril arm were conducted as intent to treat. Analyses for both arms include patients with available data for the neurocognitive tests at both timepoints.

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. A raw score (-12-12) for part C Delayed Recognition is calculated as the number of incorrectly identified words subtracted from the number of correctly identified words. Test scores are presented as standardized z scores (mean=0, sd=1) with infinite range. Higher standardized scores indicate better neurocognitive function. Change in standardized scores are compared with results from the control arm of RTOG0825 (NCT00884741).

Outcome measures

Outcome measures
Measure	Ramipril n=61 Participants Ramipril will be taken once daily by mouth. It will be titrated during the first 3 weeks of chemoradiation to the highest tolerable dose (2.5-5 mg). This dose will be taken each day until 4 months post-chemoradiation treatment (22 weeks).	RTOG 0825 Control Arm n=160 Participants RTOG 0825 was a prospective, randomized phase III trial in newly diagnosed patients with glioblastoma comparing standard radiation and temozolomide therapy with and without bevacizumab. This arm consists of patients with GBM receiving radiation with concurrent and adjuvant temozolomide per the RTOG 0825 standard arm.
Change From Baseline Neurocognitive Function at 10 Weeks - Hopkins Verbal Learning Test-Revised (HVLT-R) Delayed Recognition Standardized Score	-0.23 Change in standardized score Interval -1.13 to 0.59	0.00 Change in standardized score Interval -0.9 to 0.9

PRIMARY outcome

Timeframe: Baseline,10 weeks

Population: Analyses for the Ramipril arm were conducted as intent to treat. Analyses for both arms include patients with available data for the neurocognitive tests at both timepoints.

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. The raw score for TMT-A 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. If the assessment was not completed in the allotted time, a prorated score was calculated based on the last completed correct circle. Final prorated raw scores of total time were at least 0 seconds with no maximum limit. Test scores are presented as standardized z scores (mean=0, sd=1) with infinite range. Higher standardized scores indicate better neurocognitive function. Change in standardized scores are compared with results from the control arm of RTOG0825 (NCT00884741).

Outcome measures

Outcome measures
Measure	Ramipril n=61 Participants Ramipril will be taken once daily by mouth. It will be titrated during the first 3 weeks of chemoradiation to the highest tolerable dose (2.5-5 mg). This dose will be taken each day until 4 months post-chemoradiation treatment (22 weeks).	RTOG 0825 Control Arm n=160 Participants RTOG 0825 was a prospective, randomized phase III trial in newly diagnosed patients with glioblastoma comparing standard radiation and temozolomide therapy with and without bevacizumab. This arm consists of patients with GBM receiving radiation with concurrent and adjuvant temozolomide per the RTOG 0825 standard arm.
Change From Baseline Neurocognitive Function at 10 Weeks - Trail Making Test Part A (TMT A) Standardized Score	0.35 Change in standardized score Interval -1.38 to 1.15	0.30 Change in standardized score Interval -0.4 to 1.4

PRIMARY outcome

Timeframe: Baseline,10 weeks

Population: Analyses for the Ramipril arm were conducted as intent to treat. Analyses for both arms include patients with available data for the neurocognitive tests at both timepoints.

TMT-B requires subjects to connect 25 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 raw score TMT-B is the total time in seconds required to complete the task. If the assessment was not completed in the allotted time, a prorated score was calculated based on the last completed correct circle. Final prorated raw scores of total time were at least 0 seconds with no maximum limit. Test scores are presented as standardized z scores (mean=0, sd=1) with infinite range. Higher standardized scores indicate better neurocognitive function. Change in standardized scores are compared with results from the control arm of RTOG0825 (NCT00884741).

Outcome measures

Outcome measures
Measure	Ramipril n=61 Participants Ramipril will be taken once daily by mouth. It will be titrated during the first 3 weeks of chemoradiation to the highest tolerable dose (2.5-5 mg). This dose will be taken each day until 4 months post-chemoradiation treatment (22 weeks).	RTOG 0825 Control Arm n=160 Participants RTOG 0825 was a prospective, randomized phase III trial in newly diagnosed patients with glioblastoma comparing standard radiation and temozolomide therapy with and without bevacizumab. This arm consists of patients with GBM receiving radiation with concurrent and adjuvant temozolomide per the RTOG 0825 standard arm.
Change From Baseline Neurocognitive Function at 10 Weeks - Trail Making Test Part B (TMT B) Standardized Score	0.33 Change in standardized score Interval -2.58 to 1.32	0.00 Change in standardized score Interval -1.4 to 1.3

PRIMARY outcome

Timeframe: Baseline,10 weeks

Population: Analyses for the Ramipril arm were conducted as intent to treat. Analyses for both arms include patients with available data for the neurocognitive tests at both timepoints.

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. The raw score on the COWA (0-87) is the total number of words named across the three trials minus repetitions. Test scores are presented as standardized z scores (mean=0, sd=1) with infinite range. Higher standardized scores indicate better neurocognitive function. Change in standardized scores are compared with results from the control arm of RTOG0825 (NCT00884741).

Outcome measures

Outcome measures
Measure	Ramipril n=61 Participants Ramipril will be taken once daily by mouth. It will be titrated during the first 3 weeks of chemoradiation to the highest tolerable dose (2.5-5 mg). This dose will be taken each day until 4 months post-chemoradiation treatment (22 weeks).	RTOG 0825 Control Arm n=160 Participants RTOG 0825 was a prospective, randomized phase III trial in newly diagnosed patients with glioblastoma comparing standard radiation and temozolomide therapy with and without bevacizumab. This arm consists of patients with GBM receiving radiation with concurrent and adjuvant temozolomide per the RTOG 0825 standard arm.
Change From Baseline Neurocognitive Function at 10 Weeks - Controlled Oral Word Association Test (COWA) Standardized Scores	0.20 Change in standardized score Interval -0.31 to 0.71	0.00 Change in standardized score Interval -0.6 to 0.7

PRIMARY outcome

Timeframe: Baseline

Population: Analyses for the Ramipril arm were conducted as intent to treat. Analyses include patients with available data for the neurocognitive tests at baseline.

Shipley Institute of Living Scale 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. The score is total correct of 40 items (0-40). Higher scores indicate a better outcome.

Outcome measures

Outcome measures
Measure	Ramipril n=73 Participants Ramipril will be taken once daily by mouth. It will be titrated during the first 3 weeks of chemoradiation to the highest tolerable dose (2.5-5 mg). This dose will be taken each day until 4 months post-chemoradiation treatment (22 weeks).	RTOG 0825 Control Arm RTOG 0825 was a prospective, randomized phase III trial in newly diagnosed patients with glioblastoma comparing standard radiation and temozolomide therapy with and without bevacizumab. This arm consists of patients with GBM receiving radiation with concurrent and adjuvant temozolomide per the RTOG 0825 standard arm.
Efficacy of Ramipril of Neurocognitive Function at Baseline - Shipley Institute of Living Scale-Version 2 Vocabulary	31.0 score on a scale Interval 28.0 to 34.0	—

PRIMARY outcome

Timeframe: 10 weeks

Population: Analyses for the Ramipril arm were conducted as intent to treat.

Measured by the percent of patients who took 75% of the Ramipril doses and completed the neurocognitive battery of tests

Outcome measures

Outcome measures
Measure	Ramipril n=75 Participants Ramipril will be taken once daily by mouth. It will be titrated during the first 3 weeks of chemoradiation to the highest tolerable dose (2.5-5 mg). This dose will be taken each day until 4 months post-chemoradiation treatment (22 weeks).	RTOG 0825 Control Arm RTOG 0825 was a prospective, randomized phase III trial in newly diagnosed patients with glioblastoma comparing standard radiation and temozolomide therapy with and without bevacizumab. This arm consists of patients with GBM receiving radiation with concurrent and adjuvant temozolomide per the RTOG 0825 standard arm.
Retention Rate at 10 Weeks	48 Percentage of participants Interval 38.0 to 100.0	—

SECONDARY outcome

Timeframe: Baseline, 6 weeks, 10 weeks, 22 weeks

Population: The analysis population includes patients treated with Ramipril with assessments evaluable at each timepoint.

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. Higher scores indicate higher levels of functioning and health status/QoL.

Outcome measures

Outcome measures
Measure	Ramipril n=75 Participants Ramipril will be taken once daily by mouth. It will be titrated during the first 3 weeks of chemoradiation to the highest tolerable dose (2.5-5 mg). This dose will be taken each day until 4 months post-chemoradiation treatment (22 weeks).	RTOG 0825 Control Arm RTOG 0825 was a prospective, randomized phase III trial in newly diagnosed patients with glioblastoma comparing standard radiation and temozolomide therapy with and without bevacizumab. This arm consists of patients with GBM receiving radiation with concurrent and adjuvant temozolomide per the RTOG 0825 standard arm.
Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) - Global HRQOL Scale Baseline	66.67 score on a scale Interval 50.0 to 83.33	—
Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) - Global HRQOL Scale 6 Weeks	66.67 score on a scale Interval 50.0 to 83.33	—
Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) - Global HRQOL Scale 10 Weeks	75.00 score on a scale Interval 50.0 to 83.33	—
Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) - Global HRQOL Scale 22 Weeks	75.00 score on a scale Interval 54.17 to 83.33	—

SECONDARY outcome

Timeframe: Baseline, 6 weeks, 10 weeks, 22 weeks

Population: The analysis population includes patients treated with Ramipril with assessments evaluable at each timepoint.

Outcome measures

Outcome measures
Measure	Ramipril n=75 Participants Ramipril will be taken once daily by mouth. It will be titrated during the first 3 weeks of chemoradiation to the highest tolerable dose (2.5-5 mg). This dose will be taken each day until 4 months post-chemoradiation treatment (22 weeks).	RTOG 0825 Control Arm RTOG 0825 was a prospective, randomized phase III trial in newly diagnosed patients with glioblastoma comparing standard radiation and temozolomide therapy with and without bevacizumab. This arm consists of patients with GBM receiving radiation with concurrent and adjuvant temozolomide per the RTOG 0825 standard arm.
Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) - Physical Functioning Scale Baseline	93.33 score on a scale Interval 80.0 to 100.0	—
Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) - Physical Functioning Scale 6 Weeks	80.00 score on a scale Interval 66.67 to 93.33	—
Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) - Physical Functioning Scale 10 Weeks	86.67 score on a scale Interval 73.33 to 93.33	—
Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) - Physical Functioning Scale 22 Weeks	86.67 score on a scale Interval 80.0 to 100.0	—

SECONDARY outcome

Timeframe: Baseline, 6 weeks, 10 weeks, 22 weeks

Population: The analysis population includes patients treated with Ramipril with assessments evaluable at each timepoint.

Outcome measures

Outcome measures
Measure	Ramipril n=75 Participants Ramipril will be taken once daily by mouth. It will be titrated during the first 3 weeks of chemoradiation to the highest tolerable dose (2.5-5 mg). This dose will be taken each day until 4 months post-chemoradiation treatment (22 weeks).	RTOG 0825 Control Arm RTOG 0825 was a prospective, randomized phase III trial in newly diagnosed patients with glioblastoma comparing standard radiation and temozolomide therapy with and without bevacizumab. This arm consists of patients with GBM receiving radiation with concurrent and adjuvant temozolomide per the RTOG 0825 standard arm.
Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) - Cognitive Functioning Scale Baseline	66.67 score on a scale Interval 50.0 to 100.0	—
Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) - Cognitive Functioning Scale 6 Weeks	83.33 score on a scale Interval 66.67 to 100.0	—
Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) - Cognitive Functioning Scale 10 Weeks	83.33 score on a scale Interval 66.67 to 100.0	—
Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) - Cognitive Functioning Scale 22 Weeks	75.00 score on a scale Interval 66.67 to 100.0	—

SECONDARY outcome

Timeframe: Baseline, 6 weeks, 10 weeks, 22 weeks

Population: The analysis population includes patients treated with Ramipril with assessments evaluable at each timepoint.

Outcome measures

Outcome measures
Measure	Ramipril n=75 Participants Ramipril will be taken once daily by mouth. It will be titrated during the first 3 weeks of chemoradiation to the highest tolerable dose (2.5-5 mg). This dose will be taken each day until 4 months post-chemoradiation treatment (22 weeks).	RTOG 0825 Control Arm RTOG 0825 was a prospective, randomized phase III trial in newly diagnosed patients with glioblastoma comparing standard radiation and temozolomide therapy with and without bevacizumab. This arm consists of patients with GBM receiving radiation with concurrent and adjuvant temozolomide per the RTOG 0825 standard arm.
Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) - Social Functioning Scale 6 Weeks	66.67 score on a scale Interval 50.0 to 83.33	—
Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) - Social Functioning Scale 10 Weeks	83.33 score on a scale Interval 50.0 to 100.0	—
Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) - Social Functioning Scale 22 Weeks	66.67 score on a scale Interval 66.67 to 100.0	—
Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) - Social Functioning Scale Baseline	66.67 score on a scale Interval 50.0 to 100.0	—

SECONDARY outcome

Timeframe: Baseline, 6 weeks, 10 weeks, 22 weeks

Population: The analysis population includes patients treated with Ramipril with assessments evaluable at each timepoint.

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. Higher scores on a symptom scale represent more pronounced symptoms.

Outcome measures

Outcome measures
Measure	Ramipril n=75 Participants Ramipril will be taken once daily by mouth. It will be titrated during the first 3 weeks of chemoradiation to the highest tolerable dose (2.5-5 mg). This dose will be taken each day until 4 months post-chemoradiation treatment (22 weeks).	RTOG 0825 Control Arm RTOG 0825 was a prospective, randomized phase III trial in newly diagnosed patients with glioblastoma comparing standard radiation and temozolomide therapy with and without bevacizumab. This arm consists of patients with GBM receiving radiation with concurrent and adjuvant temozolomide per the RTOG 0825 standard arm.
Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) - Motor Dysfunction Baseline	11.11 score on a scale Interval 0.0 to 33.33	—
Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) - Motor Dysfunction 6 Weeks	11.11 score on a scale Interval 0.0 to 33.33	—
Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) - Motor Dysfunction 10 Weeks	11.11 score on a scale Interval 0.0 to 33.33	—
Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) - Motor Dysfunction 22 Weeks	11.11 score on a scale Interval 0.0 to 27.78	—

SECONDARY outcome

Timeframe: Baseline, 6 weeks, 10 weeks, 22 weeks

Population: The analysis population includes patients treated with Ramipril with assessments evaluable at each timepoint.

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. Higher scores on a symptom scale represent more pronounced symptoms.

Outcome measures

Outcome measures
Measure	Ramipril n=75 Participants Ramipril will be taken once daily by mouth. It will be titrated during the first 3 weeks of chemoradiation to the highest tolerable dose (2.5-5 mg). This dose will be taken each day until 4 months post-chemoradiation treatment (22 weeks).	RTOG 0825 Control Arm RTOG 0825 was a prospective, randomized phase III trial in newly diagnosed patients with glioblastoma comparing standard radiation and temozolomide therapy with and without bevacizumab. This arm consists of patients with GBM receiving radiation with concurrent and adjuvant temozolomide per the RTOG 0825 standard arm.
Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) - Communication Deficit Baseline	11.11 score on a scale Interval 0.0 to 38.89	—
Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) - Communication Deficit 6 Weeks	11.11 score on a scale Interval 0.0 to 33.33	—
Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) - Communication Deficit 10 Weeks	11.11 score on a scale Interval 0.0 to 33.33	—
Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) - Communication Deficit 22 Weeks	16.67 score on a scale Interval 0.0 to 33.33	—

SECONDARY outcome

Timeframe: Baseline - 22 weeks

Population: Patients with available data at baseline and each follow-up timepoint

Measured by presence of a decline of the HVLT-R Total Recall standardized score at each timepoint of cognitive assessment. Decline will be defined as a change greater than the reliable change index (RCI) for any of the individual cognitive tests is experienced for a particular patient. Clinical trial battery scores were standardized on normative data.

Outcome measures

Outcome measures
Measure	Ramipril n=75 Participants Ramipril will be taken once daily by mouth. It will be titrated during the first 3 weeks of chemoradiation to the highest tolerable dose (2.5-5 mg). This dose will be taken each day until 4 months post-chemoradiation treatment (22 weeks).	RTOG 0825 Control Arm RTOG 0825 was a prospective, randomized phase III trial in newly diagnosed patients with glioblastoma comparing standard radiation and temozolomide therapy with and without bevacizumab. This arm consists of patients with GBM receiving radiation with concurrent and adjuvant temozolomide per the RTOG 0825 standard arm.
Number of Participants With Neurocognitive Decline- Hopkins Verbal Learning Test-Revised (HVLT-R) - Total Recall Week 6	9 Participants	—
Number of Participants With Neurocognitive Decline- Hopkins Verbal Learning Test-Revised (HVLT-R) - Total Recall Week 10	10 Participants	—
Number of Participants With Neurocognitive Decline- Hopkins Verbal Learning Test-Revised (HVLT-R) - Total Recall Week 22	11 Participants	—

SECONDARY outcome

Timeframe: Baseline - 22 weeks

Population: Patients with available data at baseline and each follow-up timepoint

Measured by presence of a decline of the HVLT-R Delayed Recall standardized score at each timepoint of cognitive assessment. Decline will be defined as a change greater than the reliable change index (RCI) for any of the individual cognitive tests is experienced for a particular patient. Clinical trial battery scores were standardized on normative data.

Outcome measures

Outcome measures
Measure	Ramipril n=75 Participants Ramipril will be taken once daily by mouth. It will be titrated during the first 3 weeks of chemoradiation to the highest tolerable dose (2.5-5 mg). This dose will be taken each day until 4 months post-chemoradiation treatment (22 weeks).	RTOG 0825 Control Arm RTOG 0825 was a prospective, randomized phase III trial in newly diagnosed patients with glioblastoma comparing standard radiation and temozolomide therapy with and without bevacizumab. This arm consists of patients with GBM receiving radiation with concurrent and adjuvant temozolomide per the RTOG 0825 standard arm.
Number of Participants With Neurocognitive Decline- Hopkins Verbal Learning Test-Revised (HVLT-R) - Delayed Recall Week 6	14 Participants	—
Number of Participants With Neurocognitive Decline- Hopkins Verbal Learning Test-Revised (HVLT-R) - Delayed Recall Week 10	8 Participants	—
Number of Participants With Neurocognitive Decline- Hopkins Verbal Learning Test-Revised (HVLT-R) - Delayed Recall Week 22	6 Participants	—

SECONDARY outcome

Timeframe: Baseline - 22 weeks

Population: Patients with available data at baseline and each follow-up timepoint

Measured by presence of a decline of the HVLT-R Recognition standardized score at each timepoint of cognitive assessment. Decline will be defined as a change greater than the reliable change index (RCI) for any of the individual cognitive tests is experienced for a particular patient. Clinical trial battery scores were standardized on normative data.

Outcome measures

Outcome measures
Measure	Ramipril n=75 Participants Ramipril will be taken once daily by mouth. It will be titrated during the first 3 weeks of chemoradiation to the highest tolerable dose (2.5-5 mg). This dose will be taken each day until 4 months post-chemoradiation treatment (22 weeks).	RTOG 0825 Control Arm RTOG 0825 was a prospective, randomized phase III trial in newly diagnosed patients with glioblastoma comparing standard radiation and temozolomide therapy with and without bevacizumab. This arm consists of patients with GBM receiving radiation with concurrent and adjuvant temozolomide per the RTOG 0825 standard arm.
Number of Participants With Neurocognitive Decline- Hopkins Verbal Learning Test-Revised (HVLT-R) - Recognition Week 6	21 Participants	—
Number of Participants With Neurocognitive Decline- Hopkins Verbal Learning Test-Revised (HVLT-R) - Recognition Week 10	13 Participants	—
Number of Participants With Neurocognitive Decline- Hopkins Verbal Learning Test-Revised (HVLT-R) - Recognition Week 22	13 Participants	—

SECONDARY outcome

Timeframe: Baseline - 22 weeks

Population: Patients with available data at baseline and each follow-up timepoint.

Measured by presence of a decline of the TMT-A standardized score at each timepoint of cognitive assessment. Decline will be defined as a change greater than the reliable change index (RCI) for any of the individual cognitive tests is experienced for a particular patient. Clinical trial battery scores were standardized on normative data.

Outcome measures

Outcome measures
Measure	Ramipril n=75 Participants Ramipril will be taken once daily by mouth. It will be titrated during the first 3 weeks of chemoradiation to the highest tolerable dose (2.5-5 mg). This dose will be taken each day until 4 months post-chemoradiation treatment (22 weeks).	RTOG 0825 Control Arm RTOG 0825 was a prospective, randomized phase III trial in newly diagnosed patients with glioblastoma comparing standard radiation and temozolomide therapy with and without bevacizumab. This arm consists of patients with GBM receiving radiation with concurrent and adjuvant temozolomide per the RTOG 0825 standard arm.
Number of Participants With Neurocognitive Decline- Trail Making Test Part A (TMT A) Week 6	10 Participants	—
Number of Participants With Neurocognitive Decline- Trail Making Test Part A (TMT A) Week 10	12 Participants	—
Number of Participants With Neurocognitive Decline- Trail Making Test Part A (TMT A) Week 22	8 Participants	—

SECONDARY outcome

Timeframe: Baseline - 22 weeks

Population: Patients with available data at baseline and each follow-up timepoint.

Measured by presence of a decline of the TMT-B standardized score at each timepoint of cognitive assessment. Decline will be defined as a change greater than the reliable change index (RCI) for any of the individual cognitive tests is experienced for a particular patient. Clinical trial battery scores were standardized on normative data.

Outcome measures

Outcome measures
Measure	Ramipril n=75 Participants Ramipril will be taken once daily by mouth. It will be titrated during the first 3 weeks of chemoradiation to the highest tolerable dose (2.5-5 mg). This dose will be taken each day until 4 months post-chemoradiation treatment (22 weeks).	RTOG 0825 Control Arm RTOG 0825 was a prospective, randomized phase III trial in newly diagnosed patients with glioblastoma comparing standard radiation and temozolomide therapy with and without bevacizumab. This arm consists of patients with GBM receiving radiation with concurrent and adjuvant temozolomide per the RTOG 0825 standard arm.
Number of Participants With Neurocognitive Decline- Trail Making Test Part B (TMT B) Week 6	13 Participants	—
Number of Participants With Neurocognitive Decline- Trail Making Test Part B (TMT B) Week 10	14 Participants	—
Number of Participants With Neurocognitive Decline- Trail Making Test Part B (TMT B) Week 22	9 Participants	—

SECONDARY outcome

Timeframe: Baseline - 22 weeks

Population: Patients with available data at baseline and each follow-up timepoint.

Measured by presence of a decline of the COWA standardized score at each timepoint of cognitive assessment. Decline will be defined as a change greater than the reliable change index (RCI) for any of the individual cognitive tests is experienced for a particular patient. Clinical trial battery scores were standardized on normative data.

Outcome measures

Outcome measures
Measure	Ramipril n=75 Participants Ramipril will be taken once daily by mouth. It will be titrated during the first 3 weeks of chemoradiation to the highest tolerable dose (2.5-5 mg). This dose will be taken each day until 4 months post-chemoradiation treatment (22 weeks).	RTOG 0825 Control Arm RTOG 0825 was a prospective, randomized phase III trial in newly diagnosed patients with glioblastoma comparing standard radiation and temozolomide therapy with and without bevacizumab. This arm consists of patients with GBM receiving radiation with concurrent and adjuvant temozolomide per the RTOG 0825 standard arm.
Number of Participants With Neurocognitive Decline- Controlled Oral Word Association Test (COWA) Week 6	3 Participants	—
Number of Participants With Neurocognitive Decline- Controlled Oral Word Association Test (COWA) Week 10	3 Participants	—
Number of Participants With Neurocognitive Decline- Controlled Oral Word Association Test (COWA) Week 22	3 Participants	—

SECONDARY outcome

Timeframe: Baseline

Population: APOE samples are in storage and have not been analyzed. Due to funding constraints, the data will not be collected and the results will not be reported.

Measured by quantitative polymerase chain reaction (PCR) using patient serum via a blood test