NCT03475186|CompletedPhase 2ResultsDMCFDA Drug

Testing Ramipril to Prevent Memory Loss in People With Glioblastoma

A Single Arm, Pilot Study of Ramipril for Preventing Radiation-Induced Cognitive Decline in Glioblastoma (GBM) Patients Receiving Brain Radiotherapy

Wake Forest University Health Sciences ClinicalTrials.gov

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4 other identifiers

IRB000535313UG1CA189824-04S1NCI-2018-01807WF-1801

Study Type

interventional

Target

Locations

2 countries

Sites

423

Timeline

RegisteredMar 2018

StartedMar 2019

CompletionMar 2025

Brief Summary

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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P50-P75 for phase_2

Timeline

Completed

Started Mar 2019

Longer than P75 for phase_2

Geographic Reach

2 countries

423 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

6 years study duration

First Submitted

Initial submission to the registry

March 2, 2018

Completed

21 days until next milestone

First Posted

Study publicly available on registry

March 23, 2018

Completed

1 year until next milestone

Study Start

First participant enrolled

March 25, 2019

Completed

6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 25, 2025

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 25, 2025

Completed

12 months until next milestone

Results Posted

Study results publicly available

March 13, 2026

Completed

Last Updated

March 13, 2026

Status Verified

February 1, 2026

Enrollment Period

6 years

First QC Date

March 2, 2018

Results QC Date

November 20, 2025

Last Update Submit

February 20, 2026

Conditions

Glioblastoma Radiotherapy; Complications Cognitive Decline Chemoradiation

Keywords

MemoryBrain CancerRamipril

Outcome Measures

Primary Outcomes (8)

Change From Baseline Neurocognitive Function at 10 Weeks - Hopkins Verbal Learning Test-Revised (HVLT-R) Total Recall Standardized Score
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).
Baseline,10 weeks
Change From Baseline Neurocognitive Function at 10 Weeks - Hopkins Verbal Learning Test-Revised (HVLT-R) Delayed Recall Standardized Score
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).
Baseline,10 weeks
Change From Baseline Neurocognitive Function at 10 Weeks - Hopkins Verbal Learning Test-Revised (HVLT-R) Delayed Recognition Standardized Score
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).
Baseline,10 weeks
Change From Baseline Neurocognitive Function at 10 Weeks - Trail Making Test Part A (TMT A) Standardized Score
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).
Baseline,10 weeks
Change From Baseline Neurocognitive Function at 10 Weeks - Trail Making Test Part B (TMT B) Standardized Score
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).
Baseline,10 weeks
Change From Baseline Neurocognitive Function at 10 Weeks - Controlled Oral Word Association Test (COWA) Standardized Scores
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).
Baseline,10 weeks
Efficacy of Ramipril of Neurocognitive Function at Baseline - Shipley Institute of Living Scale-Version 2 Vocabulary
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.
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
10 weeks

Secondary Outcomes (25)

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, 6 weeks, 10 weeks, 22 weeks
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, 6 weeks, 10 weeks, 22 weeks
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, 6 weeks, 10 weeks, 22 weeks
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, 6 weeks, 10 weeks, 22 weeks
Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) - Motor Dysfunction
Baseline, 6 weeks, 10 weeks, 22 weeks
+20 more secondary outcomes

Study Arms (1)

Ramipril

EXPERIMENTAL

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).

Drug: Ramipril

Interventions

RamiprilDRUG

2.5 - 5 mg oral, 1x daily for 22 weeks

Also known as: Altace, Tritace

Ramipril

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Histologically proven diagnosis of glioblastoma or gliosarcoma (World Health Organization \[WHO\] grade IV) obtained at the time of a partial or gross total resection of the tumor. Patients who undergo a stereotactic needle biopsy alone are not eligible.
The tumor must have a supratentorial component.
History/physical examination within 14 days prior to enrollment.
The patient must have recovered from the effects of surgery, postoperative infection, and other complications before enrollment
Patient planning to receive brain RT, and concurrent and adjuvant temozolomide chemotherapy for six weeks as per standard of care therapy. Use of the Optune® (also known as Tumor Treating Fields or TTFields) device is allowed at provider discretion, but must begin after the Month 1 Post RT (10 week \[wk\]) Neurocognitive-PRO assessment.
Study drug (Ramipril) must be given \>= 21 days and ≤ 42 days after surgery.
All available brain magnetic resonance imaging (MRI) or computed tomography (CT) imaging reports from surgery to study completion must be submitted. This includes any post-operative or pre-radiation scan reports.
Eastern Cooperative Oncology Group (ECOG) 0, 1 or 2
Absolute neutrophil count (ANC) \>= 1,500 cells/mm\^3 (obtained within 14 days prior to enrollment)
Platelets \>= 100,000 cells/mm\^3 (obtained within 14 days prior to enrollment)
Hemoglobin \>= 10.0 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin \[Hgb\] \>= 10.0 g/dl is acceptable) (obtained within 14 days prior to enrollment)
Blood urea nitrogen (BUN) =\< 30 mg/dl within 14 days prior to enrollment
Creatinine =\< 1.7 mg/dl within 14 days prior to enrollment
Total bilirubin =\< 2.0 mg/dl within 14 days prior to enrollment
Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =\< 3 x normal range within 14 days prior to enrollment
+9 more criteria

You may not qualify if:

Prior allergic reaction or intolerance to angiotensin-converting-enzyme (ACE) inhibitor
Hypotension (\< 110 mg Hg systolic) at the time of enrollment
Renal insufficiency with creatinine clearance of \< 40 ml/min (at time of enrollment)
Solitary kidney or known renal artery stenosis
Current ACE inhibitor or angiotensin receptor blocker use. Patients can come off ACE inhibitors or angiotensin receptor blockers for 1 week to be eligible for this study.
Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for ≥ 2 years. (For example, carcinoma in situ of the breast, oral cavity, and cervix are all permissible).
Recurrent or multifocal malignant gliomas
Metastases detected below the tentorium or beyond the cranial vault
Prior chemotherapy or radiosensitizers for cancers of the head and neck region; note that prior chemotherapy for a different cancer is allowable, except prior temozolomide. Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment are not permitted.
Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields.
Severe active co-morbidity, defined as follows:
Acute bacterial or fungal infection requiring intravenous antibiotics at the time of enrollment
Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of enrollment.
Known HIV positivity or acquired immune deficiency syndrome (AIDS) based upon current CDC definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity.
+7 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

National Cancer Institute (NCI)collaborator
Wake Forest University Health Scienceslead

Study Sites (423)

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, 98508, United States

Location

Anchorage Radiation Therapy Center

Anchorage, Alaska, 99504, United States

Location

Alaska Breast Care and Surgery LLC