StrokePhase 1NCT02178813
The Safety of High Dose Minocycline in the Patient Population Undergoing Carotid Revascularization
A Phase 1 study testing Administration of minocycline in people with Stroke, run by University of Pittsburgh at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the safety and tolerability of high-dose minocycline in the patient population undergoing carotid revascularization procedures, namely carotid endarterectomy (CEA) and carotid artery stenting (CAS). Establishment of safety will facilitate proceeding to a phase II trial. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Stroke
- What is being tested?
- Administration of minocycline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2014to Jul 2016
- Phase
- Phase 1
- 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 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with a clinical indication for carotid revascularization (CRV) as decided by the treating physicians (the clinical indications for CRV as well as the choice of the type of CRV, either CEA or CAS, will be entirely up to the treating physicians)
- Patients who can perform the neurocognitive tests in English
- Women of childbearing age who are non-lactating and have a negative pregnancy test
- Patients in the age range of 18 years - 90 years
- Patients able to undergo MRI imaging.
- Patients that are dependable and able to return for follow-up studies and exams.
- Patients that will be in the hospital (inpatients) the day prior to the procedure for clinical purposes (for evaluation of side effects from the first dose and for overnight infusion of minocycline before the procedure)
Who cannot join
- Known hypersensitivity to tetracyclines
- Significant neurological deficit including but not limited to dense aphasia, hemi- or mono-paresis (motor strength equal or less than 3/5) or neglect.
- Baseline abnormalities on the MRI of the brain which would preclude the detection of new DWI or FLAIR changes. (e.g large areas of acute stroke, large areas of previous encephalomalacia, existing hardware such as aneurysm clips or coil masses etc.)
- Patients who are pregnant, breast-feeding, or lactating.
- Patients with a contraindication to undergo MRI, including those with pacemakers, metal implants and metal fragments within their bodies.
- Patients with abnormal liver function tests at baseline defined as a 2-fold elevation in alanine-aminotransferase.
Show all 13Show fewer
- Patients with significantly affected renal function at baseline (Creatinine equal or above 2mg/dL).
- Patients on high dose isotretinoin, vitamin A, or methotrexate
- Patients undergoing emergency carotid revascularization procedures.
- Any clinically important known medical, surgical, psychiatric or psychological disease, which would preclude completion of the protocol (such as advanced cardiac, renal or pulmonary disease).We will screen for physical and mental capacity to undergo study procedures and will obtain proxy consent for subjects who appear decisionally impaired. The screening process will be performed by the physician co-investigator obtaining the informed consent.
- Patients with a Mini-Mental Status Exam score (MMSE) of less than 21 (as determined by one of the co-investigators). Patients with MMSE score of 21 will be included.
- Patients undergoing carotid revascularization in less than 36 hours from identification, or patients who are undecided about participation less than 36 hours prior to the procedure will not be eligible for the study.
- Patients with any other factor that would make follow-up studies difficult (e.g patient is from another country, or patient is a prisoner)
Trial locations and contacts
1 site in 1 country.
United States1 site
Presbyterian Hospital
Pittsburgh, Pennsylvania, 15206
About this study
Official title: The Safety of High Dose Minocycline in the Patient Population Undergoing Carotid Revascularization. A Phase I Study
The purpose of this study is to evaluate the safety and tolerability of high-dose minocycline in the patient population undergoing carotid revascularization procedures, namely carotid endarterectomy (CEA) and carotid artery stenting (CAS). Establishment of safety will facilitate proceeding to a phase II trial.
During this trial, patients undergoing carotid revascularization procedures will receive high doses of minocycline with the following schedule (based on previous trials):
Read more
- Day prior to procedure: 800mg orally (p.o), 700mg p.o.
- Day of procedure: 600mg intravenously( i.v.), 500mg p.o.
- Day after procedure: 400mg p.o., 400mg p.o.
The levels of the drug in the plasma, standard blood tests (complete blood count, creatinine, liver function tests) as well as markers of neuronal injury (Neuron specific enolase, protein- S100b) and inflammation (C-reactive protein) will also be monitored. The patients will be monitored closely for the development of side effects from minocycline.
MRI imaging will be used to follow the development of small strokes as a result of the revascularization procedures and their resolution. The patients of this study, all receiving peri-operative minocycline, will be compared with historical controls with regards to development of small strokes and persistent of these strokes on subsequent MRI imaging.
- Conditions
- Stroke
- Being tested
- Administration of minocycline
- Keywords
- Minocycline, Neuroprotection, Stroke
- Medical subject headings
- Stroke, cyclopia sequence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Administration of minocyclineDrug
Also called Minocycline (generic name)
Administration of minocycline with the following schedule:
- Day prior to procedure: 800mg p.o., 700mg p.o.
- Day of procedure: 600mg i.v., 500mg p.o.
- Day after procedure: 400mg p.o., 400mg p.o.
| Study group | Role | What they receive |
|---|---|---|
| Administration of minocycline | Experimental | All patients in the study will receive minocycline periprocedurally with the following schedule:
* Day prior to procedure: 800mg p.o., 700mg p.o.
* Day of procedure: 600mg i.v., 500mg p.o.
* Day after procedure: 400mg p.o., 400mg p.o. Receives: Drug: Administration of minocycline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Drug Safety/Tolerability (Number of patients that require discontinuation of drug because of side effects)
The primary aim of this phase I study is to establish the safety and tolerability of this drug in patient population undergoing carotid revascularization procedures by monitoring complete blood counts, liver enzymes, renal function tests, and clinical side effects
During the above time frame (one day prior to procedure until 1 day after the procedure) the number of patients that develop any side effects requiring discontinuation of the drug will be noted.
Side effects that will lead to discontinuation of the drug are the following:
- The patient reports a clinical side effect as intolerable (nausea /vomiting, dysphagia, rash, vertigo or other side effects attributable to the administration of minocycline)
- Change in liver function tests ( 2 times elevation of alanine-aminotransferase above the normal range)
- Change in renal function tests (creatinine more than 1.5 points from baseline)
Measured: One day prior to procedure to 1 days after procedure
Secondary outcomes (4)
Progression of procedural stroke on MRI imaging
Secondary Aim 1:To examine the effect of perioperative treatment with minocycline on the number and overall volume of new neurologic ischemic lesions detected by Diffusion Weighted Imaging (DWI) within 24 hours following carotid revascularization, and on the conversion of these acute lesions to persistent changes on Magnetic Resonance Imaging (MRI) fluid-attenuated inversion recovery (FLAIR) sequences. The findings in the study's cohort of patients will be compared to historical controls
Measured: 10 days before procedure, 1 day after procedure, 1 month after procedure
Neuropsychological test performance
To examine the effect of perioperative minocycline on neuropsychological test performance. The findings in the study's cohort of patients will be compared to historical controls
Measured: 10 days prior to procedure, 1 day after procedure, 1 month after procedure
Myocardial Infarction
To examine the effect of preoperative minocycline on the incidence of myocardial infarction during carotid revascularization procedures. The findings in the study's cohort of patients will be compared to historical controls. Myocardial infarction will be investigated based on clinical grounds, electrocardiographic findings, and elevation of troponins.
Measured: Days 1, 2(procedure day), 3
Markers of neuronal injury
To examine the effect of perioperative minocycline on markers of neuronal injury (Neuron Specific Enolase and S100b) as well as inflammation C- reactive protein). The findings in the study's cohort of patients will be compared to historical controls
Measured: 1 day prior to procedure, 1 day after the procedure, 1 month after the procedure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2014 (estimated)
- Study startJul 2014
- Primary completionJul 2016
- Study completionJul 2016
Why it stopped: Study stopped prematurely because of multiple logistic difficulties
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Georgios Zenonos, University of Pittsburgh
- Investigators
- Georgios A Zenonos, MD, Principal investigator, University of Pittsburgh Resident in Neurosurgery
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02178813
- Sponsor's protocol ID
- PRO13120002
- Status last verified
- Jun 2017
- First submitted
- 23 Jun 2014
- Last updated
- 9 Jun 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Casha S, Zygun D, McGowan MD, Bains I, Yong VW, Hurlbert RJ. Results of a phase II placebo-controlled randomized trial of minocycline in acute spinal cord injury. Brain. 2012 Apr;135(Pt 4):1224-36. doi: 10.1093/brain/aws072.
PubMed 22505632
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Safety of High Dose Minocycline in the Patient Population Undergoing Carotid Revascularization. A Phase I Study
- ClinicalTrials.gov ID
- NCT02178813
- Acronym / sponsor ID
- PRO13120002
- Conditions
- Stroke
- Keywords
- Minocycline, Neuroprotection, Stroke
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study stopped prematurely because of multiple logistic difficulties
- Enrolment
- 6 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Study start
- Jul 2014
- Primary completion
- Jul 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 1 Jul 2014 (estimated)
- 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.
The purpose of this study is to evaluate the safety and tolerability of high-dose minocycline in the patient population undergoing carotid revascularization procedures, namely carotid endarterectomy (CEA) and carotid artery stenting (CAS). Establishment of safety will facilitate proceeding to a phase II trial.
During this trial, patients undergoing carotid revascularization procedures will receive high doses of minocycline with the following schedule (based on previous trials):
- Day prior to procedure: 800mg orally (p.o), 700mg p.o.
- Day of procedure: 600mg intravenously( i.v.), 500mg p.o.
- Day after procedure: 400mg p.o., 400mg p.o.
The levels of the drug in the plasma, standard blood tests (complete blood count, creatinine, liver function tests) as well as markers of neuronal injury (Neuron specific enolase, protein- S100b) and inflammation (C-reactive protein) will also be monitored. The patients will be monitored closely for the development of side effects from minocycline.
MRI imaging will be used to follow the development of small strokes as a result of the revascularization procedures and their resolution. The patients of this study, all receiving peri-operative minocycline, will be compared with historical controls with regards to development of small strokes and persistent of these strokes on subsequent MRI imaging.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Administration of minocycline | Experimental | Drug: Administration of minocyclineAll patients in the study will receive minocycline periprocedurally with the following schedule: * Day prior to procedure: 800mg p.o., 700mg p.o. * Day of procedure: 600mg i.v., 500mg p.o. * Day after procedure: 400mg p.o., 400mg p.o. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients with a clinical indication for carotid revascularization (CRV) as decided by the treating physicians (the clinical indications for CRV as well as the choice of the type of CRV, either CEA or CAS, will be entirely up to the treating physicians)
- Patients who can perform the neurocognitive tests in English
- Women of childbearing age who are non-lactating and have a negative pregnancy test
- Patients in the age range of 18 years - 90 years
- Patients able to undergo MRI imaging.
Key exclusion criteria (13 listed)
- Known hypersensitivity to tetracyclines
- Significant neurological deficit including but not limited to dense aphasia, hemi- or mono-paresis (motor strength equal or less than 3/5) or neglect.
- Baseline abnormalities on the MRI of the brain which would preclude the detection of new DWI or FLAIR changes. (e.g large areas of acute stroke, large areas of previous encephalomalacia, existing hardware such as aneurysm clips or coil masses etc.)
- Patients who are pregnant, breast-feeding, or lactating.
- Patients with a contraindication to undergo MRI, including those with pacemakers, metal implants and metal fragments within their bodies.
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 |
|---|---|---|
| Administration of minocyclineAlso: Minocycline (generic name)Administration of minocycline with the following schedule: * Day prior to procedure: 800mg p.o., 700mg p.o. * Day of procedure: 600mg i.v., 500mg p.o. * Day after procedure: 400mg p.o., 400mg p.o. | Drug | Administration of minocycline |
Primary outcome
Drug Safety/Tolerability (Number of patients that require discontinuation of drug because of side effects)
Time frame: One day prior to procedure to 1 days after procedure
The primary aim of this phase I study is to establish the safety and tolerability of this drug in patient population undergoing carotid revascularization procedures by monitoring complete blood counts, liver enzymes, renal function tests, and clinical side effects During the above time frame (one day prior to procedure until 1 day after the procedure) the number of patients that develop any side effects requiring discontinuation of the drug will be noted. Side effects that will lead to discontinuation of the drug are the following: * The patient reports a clinical side effect as intolerable (nausea /vomiting, dysphagia, rash, vertigo or other side effects attributable to the administration of minocycline) * Change in liver function tests ( 2 times elevation of alanine-aminotransferase above the normal range) * Change in renal function tests (creatinine more than 1.5 points from baseline)
4 secondary outcomes
Progression of procedural stroke on MRI imaging
Time frame: 10 days before procedure, 1 day after procedure, 1 month after procedure
Neuropsychological test performance
Time frame: 10 days prior to procedure, 1 day after procedure, 1 month after procedure
Myocardial Infarction
Time frame: Days 1, 2(procedure day), 3
Markers of neuronal injury
Time frame: 1 day prior to procedure, 1 day after the procedure, 1 month after the procedure
Results and safety
The study was stopped early (reason given: Study stopped prematurely because of multiple logistic difficulties). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2017.
- Background: PubMed 22505632Casha S, Zygun D, McGowan MD, Bains I, Yong VW, Hurlbert RJ. Results of a phase II placebo-controlled randomized trial of minocycline in acute spinal cord injury. Brain. 2012 Apr;135(Pt 4):1224-36. doi: 10.1093/brain/aws072.
Related trials for Stroke
Not yet recruiting
Temporal Interference Stimulation for Upper-Limb Motor Recovery in Early Subacute Stroke
Acute Ischemic Stroke
RecruitingObservational study
ELATE Study: Evaluating Large-vessel Acute Thrombectomy in Extended Time Window
Acute Ichemic Stroke
Recruiting
Web-Based Tele-Rehabilitation Using Action Observation and Mirror Therapy for Subacute Stroke: A Randomized Controlled Trial
Stroke, Upper Extremity Paresis
Recruiting
Early Motor-Cognitive Integrative Training on Cognitive and Motor Performance in Patients With Aneurysmal Subarachnoid Hemorrhage
Subarachnoid Aneurysm Hemorrhage
Not yet recruiting
Selective Intra-Arterial Hypothermia After Endovascular Treatment for Acute Basilar Artery Occlusion
Acute Ischemic Stroke, Basilar Artery Occlusion
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.
Georgios A Zenonos, MD principal investigator
University of Pittsburgh Resident in Neurosurgery
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Administration of minocycline in people with Stroke, run by University of Pittsburgh 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 7 inclusion and 13 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 9 Jun 2017. 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 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.
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: Study stopped prematurely because of multiple logistic difficulties). 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?
Drug Safety/Tolerability (Number of patients that require discontinuation of drug because of side effects) (time frame: One day prior to procedure to 1 days after procedure). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02178813, which also lists 1 linked publication.
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 9 Jun 2017.