|First Submitted Date ICMJE||July 30, 2012|
|First Posted Date ICMJE||August 17, 2012|
|Last Update Posted Date||November 1, 2016|
|Start Date ICMJE||August 2012|
|Primary Completion Date||June 2016 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||cerebral [11C]dLop distribution volume [ Time Frame: approximately 3 months ]
blood tests and PET data analysis and interpretation.
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT01668147 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Efavirenz and Ritonavir on Human Brian P-Glycoprotein|
|Official Title ICMJE||Influence of Efavirenz and Ritonavir on Human Brain P-Glycoprotein Activity Using PET Imaging|
The purpose of this research study is to determine the effects of ritonavir and efavirenz on the activity of P-glycoprotein in human brain.
Health self-assessment and undergo a medical history and physical examination, including a structured interview to screen for history of medical conditions, fasting blood glucose and HIV blood tests, urine HCG pregnancy test for women of childbearing potential will be performed within 24hr of study drug administration
Study visits Subjects will be studied on three occasions, with a washout between sessions. Sessions 1: Control (no pretreatment) - intravenous administration of 10 - 14 mCi of [11C] desmethyl-loperamide (dLop) with PET/CT imaging Session 2: Pretreatment with oral ritonavir for 3 days followed by intravenous administration of 10 - 14 mCi of [11C]dLOP with PET/CT imaging Session3: Pretreatment with oral efavirenz for 14 days followed by intravenous administration of 10 - 14 mCi of [11C]dLOP with PET/CT imaging
PreStudy Period Subjects who are potential candidates for the study will be educated as to the study procedures, benefits, and potential risks. They will fill out a health self-assessment and undergo a medical history and physical examination, including a structured interview to screen for history of medical conditions. Each subject who qualifies for entry into the study on the basis of inclusion/exclusion criteria, prestudy evaluations and completion of an informed consent will be assigned the next available patient number. This indicates enrollment in the study. Weight will be recorded. All enrolled subjects will undergo screening fasting blood glucose and HIV blood tests. Subjects are excluded if fasting glucose >110mg/dl (because ritonavir and efavirenz can cause glucose intolerance) or if they are HIV seropositive (since monotherapy can cause HIV resistance). Blood will be obtained for CYP3A and P-gp genotyping.
Study Period Subjects will be studied in Washington University's Center for Clinical Imaging Research (CCIR) following admission to the Clinical Research Unit for arterial (blood sampling) and peripheral venous catheter ([11C] dLop injection) insertion. Each study day will consist of an approximately 4-5 hr stay at WU Medical Center scanning, drug dosing, blood sampling and observation. Female subjects of childbearing potential will be asked to provide a urine sample for pregnancy testing on the morning of study visits. Subjects will have standard monitoring while in the scanner.
Subjects will be required to refrain from: 1) alcohol and caffeine for 24 hr prior to and during study days, 2) food/liquids after midnight the day prior to each drug administration, 3) any non-study medications (including over the counter and/or herbal) for 3 days prior to any study visit, without prior approval from the study doctor.
A blood sample is obtained once to isolate DNA and determine CYP3A and P-gp genotype. Subjects are not informed of the results of genotype tests because they are experimental, and because there are no conclusive links between genotypes and the risk of disease or adverse events from drug therapy.
Before the study sessions start, a small intravenous (IV) catheter (small plastic tube) will be placed in the patients arm or hand. This catheter will be used to inject the [11C]dLOP. IV fluids will be given throughout the study days. A second catheter will be inserted into the wrist artery for drawing periodic blood samples during the study days.
We will use Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI), two sophisticated imaging technologies to take pictures of the amount and location of [11C]dLOP in the brain at all three study visits.
The MRI will be conducted on the same day as the first PET. The MRI scanner will take pictures of the brain. An MRI scanner uses simple radio waves to create these pictures. The participant will be positioned on their back on the scanner bed and made to feel as comfortable as possible. The scanner bed will be moved inside a large tube so that the participants head and chest are inside, but they will be able to see out into the room by their feet. During the scan, participants will hear loud, rhythmic knocking sounds. Participants ears will be covered to keep the noise to a minimum. It may also be possible to listen to music through headphones during the scan. There is a speaker and a microphone in the scanner so that participants can talk to the MRI technician if there is something they need. Once the scan is begun, participants will need to lie still since movement will ruin the images of their brain. No intravenous contrast will be given to participants during the MRI scan. This procedure will take up to 30 minutes.
The PET/CT scanner uses a special radiation detection camera to produce pictures of the amount of [11C]dLOP in participants brain using a small amount of radioactive [11C]dLop. For each PET/CT scan, participants will be asked to lie still with their head in a padded holder inside the scanner. A warm, plastic mask with large eyeholes will be placed across the top of the participants face. The mask hardens as it cools and will help participants remember to keep their head still while in the scanner. The PET scan procedure will take approximately two hours from start to finish this includes set-up and approximately 60 minutes for scanning).
At all 3 study visits [11C]dLop in tracer doses up to 5.8 ug is administered intravenously in the PET scanning suite, and a series of PET images will be taken. Blood samples will be obtained from the arterial catheter during the exam to evaluate plasma concentrations of the [11C]dLop. Approximately 30 samples will be collected. Each sample will be 1ml. The total amount of blood collected during this scan is approximately 2 tablespoons.
Visit 1 is a control visit and will not include pretreatment. Patients will receive [11C] dLop intravenously, a PET/CT scan, MRI and blood sampling as described above.
Visit 2 will occur 3-30 days after Visit 1. Participants will take Ritonavir by mouth for 2 days before the PET/CT session listed above. On the study day participants will take Ritonavir 400 mg in the morning before the scan. Participants will then receive [11c] dLop, a PET/CT scan and blood sampling as described above.
Visit 3 will occur 2-4 weeks after Visit 2. Participants will take Efavirenz 600 mg by mouth every night for 14 days prior to the study day. On the study day participants will have receive [11c] dLop, a PET/CT scan and blood sampling as described above.
Participants will be monitored by a member of the research team during your scans.
|Study Type ICMJE||Interventional|
|Study Phase||Not Provided|
|Study Design ICMJE||Intervention Model: Single Group Assignment
Masking: None (Open Label)
|Condition ICMJE||Drug Effects|
|Study Arms||Experimental: study arm
Sessions 1: Control (no pretreatment) - intravenous administration of 10-14 mCi of [11C] desmethyl-loperamide (dLop) with PET/CT imaging Session 2: Pretreatment with oral ritonavir for 3 days followed by intravenous administration of 10-14 mCi of [11C]dLop with PET/CT imaging Session3: Pretreatment with oral efavirenz for 14 days followed by intravenous administration of 10-14 mCi of [11C]dLop with PET/CT imaging
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||August 2016|
|Primary Completion Date||June 2016 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages||18 Years to 40 Years (Adult)|
|Accepts Healthy Volunteers||Yes|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT01668147|
|Other Study ID Numbers ICMJE||201205135|
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||Washington University School of Medicine|
|Study Sponsor ICMJE||Washington University School of Medicine|
|Collaborators ICMJE||Not Provided|
|PRS Account||Washington University School of Medicine|
|Verification Date||October 2016|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP