Cerebral Cavernous MalformationsPhase 2NCT03474614
Effect of Oral Propranolol on mRNA Expresssion in Symptomatic Cavernous Malformation
A Phase 2 study testing Propranolol and DNA and RNA Analysis in people with Cerebral Cavernous Malformations, run by St. Joseph's Hospital and Medical Center, Phoenix at 1 site in United States.
Trial summary
This is a single center, randomized, trial that will enroll twenty (n=20) patients with a diagnosis of symptomatic cavernous malformations who are planned candidates for surgical resection by one of the investigators, and who meet all of the inclusion and exclusion criteria. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cerebral Cavernous Malformations
- What is being tested?
- Propranolol and DNA and RNA Analysis
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Jan 2018to 11 Feb 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Subject is at least 18-years of age.
- Clinical and imaging diagnosis of a symptomatic Isolated cavernous malformation or Familial cavernous malformation
- MRI Imaging Grade Type I or Type II (see Table 1)
- Patient is considered a candidate for surgical resection of their cavernous malformation
- Written and informed consent obtained prior to the study enrollment.
- Negative pregnancy test at time of enrollment for women of child-bearing potential.
- Heart rate greater than 50 beats per minute
- Systolic blood pressure > 90 mmHg
Who cannot join
- Subject is less than 18-years of age.
- History of allergy to propranolol or other beta blockers.
- Patient is already taking another beta blocker for cardiac indications.
- History of asthma presently requiring any active treatment (oral medications or inhalers).
- History of cardiac dysfunction (as defined by the New York Heart Association Functional Classification grade II, III or IV).
- Heart rate < 50 beats per minute
Show all 9Show fewer
- Systolic blood pressure < 90 mmHg
- History of diabetes and currently on any anti-hyperglycemic medication.
- Pregnant and lactating women.
Trial locations and contacts
1 site in 1 country.
United States1 site
Barrow Neurological Institute
Phoenix, Arizona, 85013
About this study
Official title: Effect of Oral Propranolol on mRNA Expression in Symptomatice Caavernous Malformation
This is a single center, randomized, trial that will enroll twenty (n=20) patients with a diagnosis of symptomatic cavernous malformations who are planned candidates for surgical resection by one of the investigators, and who meet all of the inclusion and exclusion criteria. Patients will be randomized into two groups: A Treatment group of ten (n=10) patients that will receive oral propranolol at a dose of 60mg per day (one 60mg ER capsule per day) for 7- to 10-days prior to surgery plus their usual medications, and a Control group of 10 (n=10) patients will receive only their routine medications. Currently, the only active treatment alternative for symptomatic cerebral cavernous malformations is surgery.
A control group is required to allow for a semi-quantitative comparison with mRNA and miRNA levels in the treatment group.
Read the detailed description
This is a single center, randomized, trial that will enroll twenty (n=20) patients with a diagnosis of symptomatic cavernous malformations who are planned candidates for surgical resection by one of the investigators, and who meet all of the inclusion and exclusion criteria. Patients will be randomized into two groups: A Treatment group of ten (n=10) patients that will receive oral propranolol at a dose of 60mg per day (one 60mg ER capsule per day) for 7- to 10-days prior to surgery plus their usual medications, and a Control group of 10 (n=10) patients will receive only their routine medications. Currently, the only active treatment alternative for symptomatic cerebral cavernous malformations is surgery.
A control group is required to allow for a semi-quantitative comparison with mRNA and miRNA levels in the treatment group.
- Conditions
- Cerebral Cavernous Malformations
- Being tested
- Propranolol, DNA and RNA Analysis
- Medical subject headings
- Hemangioma, Cavernous, Central Nervous System
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PropranololDrug
The medication will be administered so that patient receives a minimum of 7- days and maximum of 10-days of treatment with propranolol prior to planned surgical resection of CCM (routine care)
DNA and RNA AnalysisGenetic
During the operative procedure, a small sample of the patient's blood will be obtained and small (1 to 2cc) tissue sample from the resected cavernous malformation will be collected. The blood and tissue samples will be labeled and stored for subsequent DNA and RNA analysis
| Study group | Role | What they receive |
|---|---|---|
| treatment group | Experimental | A Treatment group of ten (n=10) patients that will receive oral propranolol at a dose of 60mg per day (one 60mg ER capsule per day) for 7- to 10-days prior to surgery plus their usual medications. Receives: Drug: Propranolol; Genetic: DNA and RNA Analysis |
| Control Group | Other | A control group of 10 (n=10) patients will receive only their routine medications (no propranolol) during the (-7 to -10 days) preoperative period. A control group (n=10) is required to allow for a semi-quantitative comparison with mRNA and miRNA levels in the treatment group. Receives: Genetic: DNA and RNA Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
To measure effects of low-dose oral propranolol on global messenger RNA (mRNA) and microRNA (miRNA) expression in the blood and tissue of patients with CCM
compare changes noted in mRNA and miRNA in blood and CCM tissue samples of patients who do and do not receive propranolol preoperatively for CCM
Measured: -7 to -10 days until surgery
Secondary outcomes (2)
To correlate treatment response to propranolol with the underlying established mutations in cerebral cavernous malformation (CCM) genes.
correlate and compare genetic mutations seen in CCM genes in tissue of patients who receive propranolol preoperatively
Measured: -7 to -10 days until surgery
Record adverse event (tolerance to) related to low-dose oral propranolol (60mg ER once daily)
Number of reported adverse events in patients taking propranolol
Measured: -7 to -10 days until surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2018
- Study start24 Jan 2018
- Primary completion11 Feb 2021
- Study completion11 Feb 2021
Why it stopped: lack of accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cerebral Cavernous MalformationsStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Two groups, intervention and control
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Joseph's Hospital and Medical Center, Phoenix
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lori Wood, St. Joseph's Hospital and Medical Center, Phoenix
- Investigators
- Joseph Zabramski, MD, Principal investigator, Barrow Brain and Spine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03474614
- Sponsor's protocol ID
- 17-0173-30-12
- Status last verified
- Apr 2024
- First submitted
- 5 Mar 2018
- Last updated
- 19 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Oral Propranolol on mRNA Expression in Symptomatice Caavernous Malformation
- ClinicalTrials.gov ID
- NCT03474614
- Acronym / sponsor ID
- 17-0173-30-12
- Conditions
- Cerebral Cavernous Malformations
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: lack of accrual
- Enrolment
- 4 participants (actual)
- Lead sponsor
- St. Joseph's Hospital and Medical Center, PhoenixUniversity, hospital or other
- Study start
- 24 Jan 2018 (actual)
- Primary completion
- 11 Feb 2021 (actual)
- Study completion
- 11 Feb 2021 (actual)
- First posted
- 22 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single center, randomized, trial that will enroll twenty (n=20) patients with a diagnosis of symptomatic cavernous malformations who are planned candidates for surgical resection by one of the investigators, and who meet all of the inclusion and exclusion criteria. Patients will be randomized into two groups: A Treatment group of ten (n=10) patients that will receive oral propranolol at a dose of 60mg per day (one 60mg ER capsule per day) for 7- to 10-days prior to surgery plus their usual medications, and a Control group of 10 (n=10) patients will receive only their routine medications. Currently, the only active treatment alternative for symptomatic cerebral cavernous malformations is surgery.
A control group is required to allow for a semi-quantitative comparison with mRNA and miRNA levels in the treatment group.
Detailed description
This is a single center, randomized, trial that will enroll twenty (n=20) patients with a diagnosis of symptomatic cavernous malformations who are planned candidates for surgical resection by one of the investigators, and who meet all of the inclusion and exclusion criteria. Patients will be randomized into two groups: A Treatment group of ten (n=10) patients that will receive oral propranolol at a dose of 60mg per day (one 60mg ER capsule per day) for 7- to 10-days prior to surgery plus their usual medications, and a Control group of 10 (n=10) patients will receive only their routine medications. Currently, the only active treatment alternative for symptomatic cerebral cavernous malformations is surgery.
A control group is required to allow for a semi-quantitative comparison with mRNA and miRNA levels in the treatment group.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Two groups, intervention and control
| Arm | Type | Receives |
|---|---|---|
| treatment group | Experimental | Drug: Propranolol, Genetic: DNA and RNA AnalysisA Treatment group of ten (n=10) patients that will receive oral propranolol at a dose of 60mg per day (one 60mg ER capsule per day) for 7- to 10-days prior to surgery plus their usual medications. |
| Control Group | Other | Genetic: DNA and RNA AnalysisA control group of 10 (n=10) patients will receive only their routine medications (no propranolol) during the (-7 to -10 days) preoperative period. A control group (n=10) is required to allow for a semi-quantitative comparison with mRNA and miRNA levels in the treatment group. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Subject is at least 18-years of age.
- Clinical and imaging diagnosis of a symptomatic Isolated cavernous malformation or Familial cavernous malformation
- MRI Imaging Grade Type I or Type II (see Table 1)
- Patient is considered a candidate for surgical resection of their cavernous malformation
- Written and informed consent obtained prior to the study enrollment.
Key exclusion criteria (9 listed)
- Subject is less than 18-years of age.
- History of allergy to propranolol or other beta blockers.
- Patient is already taking another beta blocker for cardiac indications.
- History of asthma presently requiring any active treatment (oral medications or inhalers).
- History of cardiac dysfunction (as defined by the New York Heart Association Functional Classification grade II, III or IV).
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 |
|---|---|---|
| PropranololThe medication will be administered so that patient receives a minimum of 7- days and maximum of 10-days of treatment with propranolol prior to planned surgical resection of CCM (routine care) | Drug | treatment group |
| DNA and RNA AnalysisDuring the operative procedure, a small sample of the patient's blood will be obtained and small (1 to 2cc) tissue sample from the resected cavernous malformation will be collected. The blood and tissue samples will be labeled and stored for subsequent DNA and RNA analysis | Genetic | Control Group, treatment group |
Primary outcome
To measure effects of low-dose oral propranolol on global messenger RNA (mRNA) and microRNA (miRNA) expression in the blood and tissue of patients with CCM
Time frame: -7 to -10 days until surgery
compare changes noted in mRNA and miRNA in blood and CCM tissue samples of patients who do and do not receive propranolol preoperatively for CCM
2 secondary outcomes
To correlate treatment response to propranolol with the underlying established mutations in cerebral cavernous malformation (CCM) genes.
Time frame: -7 to -10 days until surgery
Record adverse event (tolerance to) related to low-dose oral propranolol (60mg ER once daily)
Time frame: -7 to -10 days until surgery
Results and safety
The study was stopped early (reason given: lack of accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2024.
- Individual participant dataSharing planned: No
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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.
Joseph Zabramski, MD principal investigator
Barrow Brain and Spine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Propranolol and DNA and RNA Analysis in people with Cerebral Cavernous Malformations, run by St. Joseph's Hospital and Medical Center, Phoenix 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 8 inclusion and 9 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 19 Apr 2024. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
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?
The study was stopped early (reason given: lack of accrual). Results are not available in the source record.
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?
To measure effects of low-dose oral propranolol on global messenger RNA (mRNA) and microRNA (miRNA) expression in the blood and tissue of patients with CCM (time frame: -7 to -10 days until surgery). 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 19 Apr 2024.