The Safety of High Dose Minocycline in the Patient Population Undergoing Carotid Revascularization
| Status: | Not yet recruiting |
|---|---|
| Conditions: | Neurology |
| Therapuetic Areas: | Neurology |
| Healthy: | No |
| Age Range: | 18 - 90 |
| Updated: | 7/11/2015 |
| Start Date: | July 2014 |
| End Date: | July 2016 |
| Contact: | Georgios A Zenonos, MD |
| Email: | zenonosg@upmc.edu |
| Phone: | 617 817 0991 |
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):
- 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.
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.
Inclusion Criteria:
1. 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)
2. Patients who can perform the neurocognitive tests in English
3. Women of childbearing age who are non-lactating and have a negative pregnancy test
4. Patients in the age range of 18 years - 90 years
5. Patients able to undergo MRI imaging.
6. Patients that are dependable and able to return for follow-up studies and exams.
7. 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)
Exclusion Criteria:
1. Known hypersensitivity to tetracyclines
2. Significant neurological deficit including but not limited to dense aphasia, hemi- or
mono-paresis (motor strength equal or less than 3/5) or neglect.
3. 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.)
4. Patients who are pregnant, breast-feeding, or lactating.
5. Patients with a contraindication to undergo MRI, including those with pacemakers,
metal implants and metal fragments within their bodies.
6. Patients with abnormal liver function tests at baseline defined as a 2-fold elevation
in alanine-aminotransferase.
7. Patients with significantly affected renal function at baseline (Creatinine equal or
above 2mg/dL).
8. Patients on high dose isotretinoin, vitamin A, or methotrexate
9. Patients undergoing emergency carotid revascularization procedures.
10. 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.
11. 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.
12. 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.
13. Patients with any other factor that would make follow-up studies difficult (e.g
patient is from another country, or patient is a prisoner)
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