Drug Effects
Conditions
Keywords
PET Imaging, Efavirenz, Ritonavir, [11C] desmethyl-loperamide, Healthy volunteers
Brief summary
To determine the effects of ritonavir and efavirenz on the activity of P-glycoprotein in human brain.
Detailed description
Sequential crossover using tracer 11C-desmethylloperamide, a substrate for brain P-glycoprotein, and positron emission tomography (PET), administered after nothing (control), oral ritonavir (3d), and oral efavirenz (14d) with washout in between
Interventions
DRUG[11C] desmethyl-loperamide
IV administration of 10-14 mCi of \[11C\] desmethyl-loperamide with PET/CT imaging
OTHERControl - no pretreatment
Session 1: IV administration of 10-14 mCi \[11C\] desmethyl-loperamide (dLop) with PET/CT imaging and brain MRI
DRUGOral ritonavir
Session 2: Pretreatment with oral ritonavir for 3 days followed by IV administration of 10-14 mCi \[11C\]dLop with PET/CT imaging and brain MRI
DRUGOral efavirenz
Session 3: Pretreatment with oral efavirenz for 14 days followed by IV administration of 10-14 mCi \[11C\]dLop with PET/CT imaging and brain MRI
Sponsors
Washington University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or non-pregnant female, 18-40 yr old * Good general health with no remarkable medical conditions * BMI \< 33 * Provide informed consent
Exclusion criteria
* Known history of liver or kidney disease * History of major medical conditions * HIV seropositive * Fasting blood glucose \> 110 mg/dl * Family history of type 2 diabetes * Use of prescription or non prescription medications, herbals or foods known to be metabolized by or altering P-glycoprotein or CYP3A activity (hormonal birth control medications are acceptable if alternative means of contraception are used) * Females who are pregnant or nursing * Females taking hormonal contraceptives who are unwilling to use alternative means of contraception * Contraindications to MRI * Contraindications to PET scanning
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cerebral [11C]dLop Distribution Volume | 1 day |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Study Arm Session 1: Control (no pretreatment) - IV 10-14 mCi of \[11C\] desmethyl-loperamide (dLop) with PET/CT imaging Session 2: Pretreatment with oral ritonavir for 3 days followed by IV 10-14 mCi of \[11C\]dLop with PET/CT imaging Session 3: Pretreatment with oral efavirenz for 14 days followed by IV 10-14 mCi of \[11C\]dLop with PET/CT imaging
\[11C\] desmethyl-loperamide: IV administration of 10-14 mCi of \[11C\] desmethyl-loperamide with PET/CT imaging after control, ritonavir or efavirenz | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 6 |
Baseline characteristics
| Characteristic | Study Arm |
|---|---|
| Age, Continuous | 27 years STANDARD_DEVIATION 6 |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 13 | 0 / 13 |
| other Total, other adverse events | 0 / 13 | 2 / 13 | 4 / 13 |
| serious Total, serious adverse events | 0 / 13 | 0 / 13 | 0 / 13 |
Outcome results
Primary
Cerebral [11C]dLop Distribution Volume
Time frame: 1 day
Population: 0 Participants Analyzed/Assigned. The PI has left the institution. Sincere efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available.