Cerebral EdemaPhase 1/2NCT02460874
Glyburide vs Placebo as Prophylaxis Against Cerebral Edema in Patients Receiving Radiosurgery for Brain Metastases (RAD 1502/UAB 1593)
A Phase 1/2 study testing Glyburide in people with Cerebral Edema and Brain Metastases, run by University of Alabama at Birmingham at 1 site in United States.
Trial summary
Primary Objectives: Pilot Portion: To determine the feasibility and safety of administering oral glyburide to non-diabetic patients receiving stereotactic radiosurgery (SRS) for newly diagnosed brain metastases. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cerebral Edema, Brain Metastases
- What is being tested?
- Glyburide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Aug 2017to 19 May 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with newly diagnosed brain metastases deemed to be eligible for radiosurgery.
- Subject must have cytologically or histologically confirmed malignancy (this is the original malignancy, not the brain metastases).
- A diagnostic contrast-enhanced MRI of the brain must be performed within 60 days prior to registration. The contrast-enhancing intraparenchymal brain tumor must be well visualized.
- History and physical with neurological examination, height, and weight within 14 days prior to registration
- No dexamethasone use (or any other corticosteroid use with the purpose of treating cerebral edema) starting 5 days prior to SRS. Patients may be tapered to meet this criterion if deemed safe by the treating physician.
- Women of child-bearing potential (e.g. not post-menopausal or permanently sterilized women) must have a negative pregnancy test obtained within 14 days prior to registration. This is to prevent potential harm to the fetus by glyburide and radiotherapy.
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- CBC with differential and CMP including Liver Function Tests (LFTs) obtained within 14 days prior to registration and meeting the following requirements:
- Creatinine Clearance ≥ 50 mL/min.
- Total Bilirubin < 1.5 x the upper limit of normal (ULN).
- ALT and AST ≤ 2.5 x ULN.
- Glucose ≥ 80 mg/dL.
- Hemoglobin ≥ 7 mg/dL.
- Absolute Neutrophil Count > 100 cells/mm3.
- For the Randomized Portion only: Subject must have at least 2 of the following risk factors: {For the Pilot Portion, it is not required that patients have the risk factors mentioned in Inclusion Criteria 9.}
- Pretreatment Edema/Tumor ratio (≥ 35:1) as contoured on a baseline MRI obtained at most 60 days prior to registration. Patients are allowed to have Whole Brain Radiotherapy (WBRT) or corticosteroid use between the time of pretreatment MRI and SRS (as long as the corticosteroids can be safely tapered at least 5 days prior to the treatment planning MRI and WBRT is at least 4 days prior to registration).
- Greater than 40 pack year history of smoking cigarettes.
- Whole Brain Radiotherapy at least 4 days and no more than 1 year prior to registration.
- RPA Class III.
Who cannot join
- Known sulfonylurea treatment within 7 days prior to registration. Sulfonylureas include glyburide/glibenclamide (Diabeta, Glynase); glyburide plus metformin (Glucovance); glimepiride (Amaryl); repaglinide (Prandin); nateglinide (Starlix); glipizide (Glucotrol, GlibeneseR, MinodiabR); gliclazide (DiamicronR); tolbutamide (Orinase, Tolinase); and glibornuride (Glutril).
- Diffuse Leptomeningeal metastases.
- Known allergy to sulfa or specific allergy to sulfonylurea drugs.
- Use of VEGF inhibitors within 10 days prior to registration.
- Allergy to gadolinium.
- Type 1 diabetes mellitus or Type 2 diabetes mellitus actively receiving treatment.
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- Cognitive impairment that precludes a patient from acting as his or her own agent to provide informed consent.
- Concurrent use of Bosentan.
- Any major medical illnesses or psychiatric impairments that in the treating physician's opinion will prevent administration or completion of protocol therapy ( which may include patients who are elderly, debilitated, or malnourished persons and/or those with renal, hepatic or adrenal insufficiency).
- Pregnant or breast feeding women due potential damage to the fetus
- Inability to undergo MRI or SRS (e.g. due to safety reasons such as presence of a pacemaker).
- Deemed by the treating physician to be unable to eat regular meals.
- Patients currently on beta blockers.
- Patients with a known diagnosis of ongoing alcoholism/alcohol abuse.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Alabama at Birmingham (UAB) Department of Radiation Oncology
Birmingham, Alabama, 35249
About this study
Official title: A Pilot Study and Phase II Double Blind Placebo Controlled Randomized Trial Examining the Safety and Efficacy of Glyburide as Prophylaxis Against Cerebral Edema in Patients Receiving Radiosurgery for Brain Metastases
Primary Objectives:
Pilot Portion: To determine the feasibility and safety of administering oral glyburide to non-diabetic patients receiving stereotactic radiosurgery (SRS) for newly diagnosed brain metastases.
Randomized Portion: To determine the number of patients with newly diagnosed brain metastases who have an increase in edema as measured on volumetric FLAIR imaging and the number of patients that require dexamethasone administration (or any corticosteroid administration with the purpose of treating cerebral edema) from the day of SRS to one month follow-up MRI in the group receiving glyburide versus placebo.
Read the detailed description
Many patients with cancer that has spread to the brain have side effects caused by swelling around the tumors. A common treatment for this swelling is a medicine called dexamethasone. Dexamethasone is a steroid. Long-term use of steroids has several known side effects.
Recent studies have shown that a drug commonly used in to control high blood sugar in diabetes, called glyburide, can decrease brain swelling in patients with brain damage or stroke. Animal studies have shown that this drug may also reduce swelling from tumors in the brain. Researchers are interested in whether glyburide could treat brain swelling as well as dexamethasone with fewer side effects.
This study is being done to see whether glyburide is safe to be used in patients without diabetes in combination with receiving SRS for brain metastases. This study will also find out if glyburide will decrease brain swelling in patients that get radiosurgery (SRS) for brain metastases. This study will also find out if taking glyburide will decrease the chance of needing steroids due to brain swelling that is causing symptoms. It is not yet known, but it is the investigators' hope that glyburide will both decrease brain swelling and lessen the chance of needing steroids.
- Conditions
- Cerebral Edema, Brain Metastases
- Being tested
- Glyburide, Placebo
- Keywords
- Brain Metastases, Stereotactic Radiosurgery, Glyburide
- Medical subject headings
- Brain Edema, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GlyburideDrug
1.25mg, twice a day
PlaceboOther
1.25mg, twice a day
| Study group | Role | What they receive |
|---|---|---|
| Pilot Portion | Experimental | Step 1: Patients with brain metastases requiring SRS and not taking corticosteroids 5 days prior to SRS. Treatment planning MRI may be done within 21 days prior to SRS treatment.
Step 2: Take Glyburide 1.25mg (twice a day by mouth) beginning 5 days prior to SRS. Receive glucose monitoring materials and blood glucose education- begin glucose monitoring (4 times a day).
Step 3: 1 week after SRS, return to clinic to review glucose logs- continue glyburide and blood glucose monitoring.
Step 4: 1 month after SRS, discontinue both glyburide and blood glucose monitoring, undergo MRI.
Step 5: 3 months after SRS, undergo MRI. Receives: Drug: Glyburide |
| Randomized Portion | Placebo comparator | Step 1: Patients with brain metastases requiring SRS and not taking corticosteroids 5 days prior to SRS.Treatment planning MRI may be done within 21 days prior to SRS treatment.
Step 2: Randomization (1:1)
* Group 1: take Glyburide (1.25mg, twice a day by mouth) beginning 5 days prior to SRS. Receive glucose monitoring materials and blood glucose education. Begin glucose monitoring (once a day) {This portion will be double blinded}.
* Group 2: Take Placebo (1 pill, twice a day by mouth) beginning 5 days prior to SRS. Receive glucose monitoring materials and blood glucose education. Begin glucose monitoring (once a day) {This portion will be double blinded}.
Step 3: 1 week after SRS, return to clinic to review glucose logs, continue investigation medication, but discontinue glucose monitoring.
Step 4: 1 month after SRS, discontinue investigation medication, undergo MRI.
Step 5: 3 months after SRS, undergo MRI. Receives: Drug: Glyburide; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose Limiting Toxicities (DLTs)
Assessed between the time of glyburide initiation and the time of the one month follow-up MRI.
Measured: 4 months
Randomized Portion: Occurrence of Edema Increase and Initiation of Dexamethasone (or Any Corticosteroid Administration With the Purpose of Treating Cerebral Edema)
Assessed between the time of SRS and the time of the one month follow-up MRI.
Measured: 4 months
Secondary outcomes (5)
Number of Participants Administered Dexamethasone (or Any Corticosteroid Administration With the Purpose of Treating Cerebral Edema)
Measured between the time of SRS and the time of the one and three month post SRS MRI scans.
Measured: 4 months
Number of Participants With CTCAE Version 4.0 Reportable Toxicities of Grades 2-5.
Incidence of CTCAE version 4.0 reportable toxicities of grades 2-5.
Measured: 4 months
Number of Participants With CTCAE Version 4.0 Reportable Toxicities of Grades 1-2 Cardiac Disorders or Hepatobiliary Disorders.
Incidence of CTCAE version 4.0 reportable toxicities of grades 1-2 Cardiac Disorders or Hepatobiliary Disorders.
Measured: Up to 4 months
Number of Participants With Cerebral Edema Increase as Measured on FLAIR Volumetric Imaging
Defined from MRI taken at the time of SRS and the time of the one and three month post SRS MRI scans.
Measured: 4 months
Number of Participants With Absolute Volume Change of Index Tumor(s)
Absolute volume change of index tumor(s) that received radiosurgery as manually contoured by the radiation oncologist defined from T1 post gadolinium sequences at the time of SRS and the time of the one and three month post SRS MRI scans.
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2015 (estimated)
- Study start16 Aug 2017
- Primary completion19 May 2021
- Study completion19 May 2021
Why it stopped: Slow accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cerebral EdemaStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Drexell Hunter Boggs, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02460874
- Sponsor's protocol ID
- IRB-16063003
- Status last verified
- Aug 2022
- First submitted
- 28 May 2015
- Last updated
- 21 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study and Phase II Double Blind Placebo Controlled Randomized Trial Examining the Safety and Efficacy of Glyburide as Prophylaxis Against Cerebral Edema in Patients Receiving Radiosurgery for Brain Metastases
- ClinicalTrials.gov ID
- NCT02460874
- Acronym / sponsor ID
- IRB-16063003
- Conditions
- Cerebral Edema, Brain Metastases
- Keywords
- Brain Metastases, Stereotactic Radiosurgery, Glyburide
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual
- Enrolment
- 1 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Study start
- 16 Aug 2017 (actual)
- Primary completion
- 19 May 2021 (actual)
- Study completion
- 19 May 2021 (actual)
- First posted
- 3 Jun 2015 (estimated)
- Results
- Posted 21 Sep 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary Objectives:
Pilot Portion: To determine the feasibility and safety of administering oral glyburide to non-diabetic patients receiving stereotactic radiosurgery (SRS) for newly diagnosed brain metastases.
Randomized Portion: To determine the number of patients with newly diagnosed brain metastases who have an increase in edema as measured on volumetric FLAIR imaging and the number of patients that require dexamethasone administration (or any corticosteroid administration with the purpose of treating cerebral edema) from the day of SRS to one month follow-up MRI in the group receiving glyburide versus placebo.
Detailed description
Many patients with cancer that has spread to the brain have side effects caused by swelling around the tumors. A common treatment for this swelling is a medicine called dexamethasone. Dexamethasone is a steroid. Long-term use of steroids has several known side effects.
Recent studies have shown that a drug commonly used in to control high blood sugar in diabetes, called glyburide, can decrease brain swelling in patients with brain damage or stroke. Animal studies have shown that this drug may also reduce swelling from tumors in the brain. Researchers are interested in whether glyburide could treat brain swelling as well as dexamethasone with fewer side effects.
This study is being done to see whether glyburide is safe to be used in patients without diabetes in combination with receiving SRS for brain metastases. This study will also find out if glyburide will decrease brain swelling in patients that get radiosurgery (SRS) for brain metastases. This study will also find out if taking glyburide will decrease the chance of needing steroids due to brain swelling that is causing symptoms. It is not yet known, but it is the investigators' hope that glyburide will both decrease brain swelling and lessen the chance of needing steroids.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pilot Portion | Experimental | Drug: GlyburideStep 1: Patients with brain metastases requiring SRS and not taking corticosteroids 5 days prior to SRS. Treatment planning MRI may be done within 21 days prior to SRS treatment. Step 2: Take Glyburide 1.25mg (twice a day by mouth) beginning 5 days prior to SRS. Receive glucose monitoring materials and blood glucose education- begin glucose monitoring (4 times a day). Step 3: 1 week after SRS, return to clinic to review glucose logs- continue glyburide and blood glucose monitoring. Step 4: 1 month after SRS, discontinue both glyburide and blood glucose monitoring, undergo MRI. Step 5: 3 months after SRS, undergo MRI. |
| Randomized Portion | Placebo comparator | Drug: Glyburide, Other: PlaceboStep 1: Patients with brain metastases requiring SRS and not taking corticosteroids 5 days prior to SRS.Treatment planning MRI may be done within 21 days prior to SRS treatment. Step 2: Randomization (1:1) * Group 1: take Glyburide (1.25mg, twice a day by mouth) beginning 5 days prior to SRS. Receive glucose monitoring materials and blood glucose education. Begin glucose monitoring (once a day) {This portion will be double blinded}. * Group 2: Take Placebo (1 pill, twice a day by mouth) beginning 5 days prior to SRS. Receive glucose monitoring materials and blood glucose education. Begin glucose monitoring (once a day) {This portion will be double blinded}. Step 3: 1 week after SRS, return to clinic to review glucose logs, continue investigation medication, but discontinue glucose monitoring. Step 4: 1 month after SRS, discontinue investigation medication, undergo MRI. Step 5: 3 months after SRS, undergo MRI. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Patients with newly diagnosed brain metastases deemed to be eligible for radiosurgery.
- Subject must have cytologically or histologically confirmed malignancy (this is the original malignancy, not the brain metastases).
- A diagnostic contrast-enhanced MRI of the brain must be performed within 60 days prior to registration. The contrast-enhancing intraparenchymal brain tumor must be well visualized.
- History and physical with neurological examination, height, and weight within 14 days prior to registration
- No dexamethasone use (or any other corticosteroid use with the purpose of treating cerebral edema) starting 5 days prior to SRS. Patients may be tapered to meet this criterion if deemed safe by the treating physician.
Key exclusion criteria (14 listed)
- Known sulfonylurea treatment within 7 days prior to registration. Sulfonylureas include glyburide/glibenclamide (Diabeta, Glynase); glyburide plus metformin (Glucovance); glimepiride (Amaryl); repaglinide (Prandin); nateglinide (Starlix); glipizide (Glucotrol, GlibeneseR, MinodiabR); gliclazide (DiamicronR); tolbutamide (Orinase, Tolinase); and glibornuride (Glutril).
- Diffuse Leptomeningeal metastases.
- Known allergy to sulfa or specific allergy to sulfonylurea drugs.
- Use of VEGF inhibitors within 10 days prior to registration.
- Allergy to gadolinium.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Glyburide1.25mg, twice a day | Drug | Pilot Portion, Randomized Portion |
| Placebo1.25mg, twice a day | Other | Randomized Portion |
Primary outcome
Number of Participants With Dose Limiting Toxicities (DLTs)
Time frame: 4 months
Assessed between the time of glyburide initiation and the time of the one month follow-up MRI.
Randomized Portion: Occurrence of Edema Increase and Initiation of Dexamethasone (or Any Corticosteroid Administration With the Purpose of Treating Cerebral Edema)
Time frame: 4 months
Assessed between the time of SRS and the time of the one month follow-up MRI.
5 secondary outcomes
Number of Participants Administered Dexamethasone (or Any Corticosteroid Administration With the Purpose of Treating Cerebral Edema)
Time frame: 4 months
Number of Participants With CTCAE Version 4.0 Reportable Toxicities of Grades 2-5.
Time frame: 4 months
Number of Participants With CTCAE Version 4.0 Reportable Toxicities of Grades 1-2 Cardiac Disorders or Hepatobiliary Disorders.
Time frame: Up to 4 months
Number of Participants With Cerebral Edema Increase as Measured on FLAIR Volumetric Imaging
Time frame: 4 months
Number of Participants With Absolute Volume Change of Index Tumor(s)
Time frame: 4 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Glyburide in people with Cerebral Edema and Brain Metastases, run by University of Alabama at Birmingham at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Sep 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose Limiting Toxicities (DLTs) (time frame: 4 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2022.