HIV-Associated Cognitive Motor ComplexNCT01547754
Mild Neurocognitive Disorder in HIV Infection of the Brain
An observational study of HIV-Associated Cognitive Motor Complex, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
Background: Some people with human immunodeficiency virus (HIV) develop problems with thinking and concentration when the virus affects the brain. This is known as mild neurocognitive disorder (MND). Research has shown that some HIV medications do not get through the blood brain barrier very well. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- HIV-Associated Cognitive Motor Complex
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Jan 2012to 25 Aug 2014
- Phase
- Observational
- 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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subjects must be between 18 and 60 years of age.
- Capable of providing informed consent.
- Ambulatory at initial visit.
- Speak English fluently
- For HIV seropositive subjects:
- Confirmation of HIV antibody status by ELISA and Western Blot
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- Documented HIV-infection for at least one year
- On a stable antiretroviral regimen that includes a protease inhibitor for at least 3 months and have a viral load < 400 copies/mL.
- Have a primary care physician.
- Specific inclusion criteria for mild neurocognitive disorder are as follows:
- Subject has an acquired mild-to-moderate impairment in cognitive function documented by a score of at least 1 SD below demographically corrected norms on testing of at least two different cognitive domains.
- The cognitive impairment interferes, at least mildly, with activities of daily living, as determined by neuropsychological interview.
- The impairment does not meet DSM-IV criteria for delirium or dementia.
- The impairment is not fully explained by co-morbid conditions.
Who cannot join
- Current Axis I psychiatric illness or severe systemic disease (other than HIV and MND) based on history and physical exam that would make study participation unsafe in the opinion of the investigators.
- Current alcohol use greater than 14 drinks per week for men and 7 drinks per week for women.
- Laboratory tests with clinically significant abnormalities. Normal organ and marrow function are defined as: total leukocyte count greater than or equal to 3000 cells/ul, ANC greater than or equal to 1500 cells/ul, platelet count greater than or equal to 100,000 cells/ul, serum creatinine less than or equal to 2.0 times upper limit of normal, hemoglobin greater than or equal to 9.0 g/dL, serum calcium <12.0 mg/dL, AST/ALT less than or equal to 1.5 times the upper limit of normal, PT 1.5 upper limit of normal.
- EKG finding consistent with ischemic heart disease unless there is documentation of normal cardiac function (e.g., normal stress test or echocardiogram results).
- Previous research radiation exposure (X-rays, PET scans etc.) that, with the study PET scans, would exceed annual research limits.
- Pregnancy or breast feeding.
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- Evidence of brain disease such as stroke, tumor, epilepsy, traumatic brain injury, or any neurodegenerative disease on history or on screening MRI.
- Inability to lay on his/her back for long periods, severe claustrophobia, pacemaker, or other contraindication for MRI.
- More than moderate hypertension, defined as blood pressure greater than or equal to 160/95 at the time of screening.
- Current use of illicit drugs based on positive result on urine screen for illicit drugs at the time of screening.
- Subjects taking medications, other than anti-retroviral drugs, that are known substrates of P-gp that cannot be safely discontinued for this study. Anti-retroviral drugs, particularly protease inhibitors such as ritonavir, that are P-gp substrates are allowed.
- Note: The rationale for the exclusion criteria for alcohol use is to avoid alcohol-related cognitive impairment as a confounding factor.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Inflammation and Function of P-gp in HIV Infection of Brain
Background:
- Some people with human immunodeficiency virus (HIV) develop problems with thinking and concentration when the virus affects the brain. This is known as mild neurocognitive disorder (MND). Research has shown that some HIV medications do not get through the blood brain barrier very well. P-glycoprotein (P-gp) is a brain protein that is part of the blood brain barrier. Differences in the activity of P-gp may help explain why some people with HIV develop MND. It is also possible that MND is partly due to inflammation in the brain. Researchers want to study P-gp and its effect on MND and HIV infection.
Read more
Objectives:
- To study P-gp and brain inflammation related to HIV infection.
Eligibility:
- Individuals between 18 and 60 years of age who have HIV and either do or do not have MND.
- Healthy volunteers between 18 and 60 years of age.
Design:
- Participants will be screened with a medical history and physical exam. Blood and urine samples will be collected.
- Participants will have one outpatient visit and one 3-day inpatient stay.
- At the outpatient visit, participants will provide blood samples and have a lumbar puncture (spinal tap). The spinal tap will collect cerebrospinal fluid for study.
- At the inpatient visit, participants will have two positron emission tomography (PET) scans of the brain. These scans will study brain activity and possible inflammation. One scan will involve a study drug called tariquidar, which blocks the activity of P-gp. A second lumbar puncture will be done before the first PET scan. Blood and urine samples will be collected daily.
Read the detailed description
Objective:
To determine the relationship among neuroinflammation, Permeability-glycoprotein (P-gp) function and mild neurocognitive disorder (MND), a cognitive disorder associated with HIV infection.
Study Population:
HIV seropositive subjects with MND, HIV seropositive subjects with normal cognitive function, and HIV seronegative control subjects.
Design:
Subjects will undergo history and physical exam, screening laboratory tests, EKG, brain MRI and neuropsychological evaluation. HIV-seropositive subjects will be stratified based on results of neuropsychological evaluation into HIV-seropositive controls (i.e., cognitively normal) and HIV-seropositive with MND. All subjects will receive brain PET imaging with [11C]dLop after P-gp blockade to measure the function of P-gp at the blood-brain barrier. P-gp will be blocked prior to the PET scan with tariquidar. HIV-seropositive subjects will receive one lumbar puncture at baseline and one lumbar puncture after P-gp blockade with tariquidar to measure CSF concentrations of anti-retroviral medications and to measure biomarkers of blood-brain barrier integrity and inflammation in the CSF. HIV-seronegative subjects will receive one lumbar puncture at baseline to measure biomarkers of blood-brain barrier integrity and inflammation in the CSF.
Outcome Measures:
The main outcome measures of the study is brain uptake of [11C]dLop in response to P-gp blockade with tariquidar. We will correct for individual metabolism of tariquidar by measuring the plasma concentration of tariquidar during the P-gp blocked scan.
As a secondary outcome measure, concentrations of anti-retroviral medications in CSF will be measured in HIV seropositive subjects with and without MND. CSF concentrations will be used as a surrogate marker for CNS delivery of anti-retroviral drugs.
- Conditions
- HIV-Associated Cognitive Motor Complex
- Keywords
- Neuroinflammation, HIV, Positron Emission Tomograhy (PET), Mild Neurocognitive Disorder, P-Glycoprotein, Mild Cognitive Disorder, Healthy Volunteer, HV
- Medical subject headings
- AIDS Dementia Complex, Neuroinflammatory Diseases, Neurocognitive Disorders
What is being measured
The primary outcome is the main question the study is designed to answer.
Brain uptake of [11C]dLop after pharmacological challenge with the P-gp inhibitor tariquidar.
Secondary outcomes (1)
Cerebrospinal fluid concentrations of antiretroviral drugs and inflammatory markers.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2012 (estimated)
- Study start9 Jan 2012
- Study completion25 Aug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HIV-Associated Cognitive Motor ComplexStudies of the same condition, open and under way.
- More trials run by National Institute of Mental Health (NIMH)The 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
- Observational
- Time perspective
- Prospective
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Investigators
- Robert B Innis, M.D., Principal investigator, National Institute of Mental Health (NIMH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01547754
- Sponsor's protocol ID
- 120059
- Other IDs
- 12-M-0059
- Status last verified
- 25 Aug 2014
- First submitted
- 6 Mar 2012
- Last updated
- 16 Dec 2019
- Results posted
- No
Publications
Kaddoumi A, Choi SU, Kinman L, Whittington D, Tsai CC, Ho RJ, Anderson BD, Unadkat JD. Inhibition of P-glycoprotein activity at the primate blood-brain barrier increases the distribution of nelfinavir into the brain but not into the cerebrospinal fluid. Drug Metab Dispos. 2007 Sep;35(9):1459-62. doi: 10.1124/dmd.107.016220. Epub 2007 Jun 25.
PubMed 17591677Langford D, Grigorian A, Hurford R, Adame A, Ellis RJ, Hansen L, Masliah E. Altered P-glycoprotein expression in AIDS patients with HIV encephalitis. J Neuropathol Exp Neurol. 2004 Oct;63(10):1038-47. doi: 10.1093/jnen/63.10.1038.
PubMed 15535131Loscher W, Potschka H. Drug resistance in brain diseases and the role of drug efflux transporters. Nat Rev Neurosci. 2005 Aug;6(8):591-602. doi: 10.1038/nrn1728.
PubMed 16025095
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inflammation and Function of P-gp in HIV Infection of Brain
- ClinicalTrials.gov ID
- NCT01547754
- Acronym / sponsor ID
- 120059
- Conditions
- HIV-Associated Cognitive Motor Complex
- Keywords
- Neuroinflammation, HIV, Positron Emission Tomograhy (PET), Mild Neurocognitive Disorder, P-Glycoprotein, Mild Cognitive Disorder, Healthy Volunteer, HV
- Study type
- Observational
- Recruitment status
- Terminated
- Enrolment
- 8 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 9 Jan 2012
- Study completion
- 25 Aug 2014
- First posted
- 8 Mar 2012 (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.
Background:
- Some people with human immunodeficiency virus (HIV) develop problems with thinking and concentration when the virus affects the brain. This is known as mild neurocognitive disorder (MND). Research has shown that some HIV medications do not get through the blood brain barrier very well. P-glycoprotein (P-gp) is a brain protein that is part of the blood brain barrier. Differences in the activity of P-gp may help explain why some people with HIV develop MND. It is also possible that MND is partly due to inflammation in the brain. Researchers want to study P-gp and its effect on MND and HIV infection.
Objectives:
- To study P-gp and brain inflammation related to HIV infection.
Eligibility:
- Individuals between 18 and 60 years of age who have HIV and either do or do not have MND.
- Healthy volunteers between 18 and 60 years of age.
Design:
- Participants will be screened with a medical history and physical exam. Blood and urine samples will be collected.
- Participants will have one outpatient visit and one 3-day inpatient stay.
- At the outpatient visit, participants will provide blood samples and have a lumbar puncture (spinal tap). The spinal tap will collect cerebrospinal fluid for study.
- At the inpatient visit, participants will have two positron emission tomography (PET) scans of the brain. These scans will study brain activity and possible inflammation. One scan will involve a study drug called tariquidar, which blocks the activity of P-gp. A second lumbar puncture will be done before the first PET scan. Blood and urine samples will be collected daily.
Detailed description
Objective:
To determine the relationship among neuroinflammation, Permeability-glycoprotein (P-gp) function and mild neurocognitive disorder (MND), a cognitive disorder associated with HIV infection.
Study Population:
HIV seropositive subjects with MND, HIV seropositive subjects with normal cognitive function, and HIV seronegative control subjects.
Design:
Subjects will undergo history and physical exam, screening laboratory tests, EKG, brain MRI and neuropsychological evaluation. HIV-seropositive subjects will be stratified based on results of neuropsychological evaluation into HIV-seropositive controls (i.e., cognitively normal) and HIV-seropositive with MND. All subjects will receive brain PET imaging with [11C]dLop after P-gp blockade to measure the function of P-gp at the blood-brain barrier. P-gp will be blocked prior to the PET scan with tariquidar. HIV-seropositive subjects will receive one lumbar puncture at baseline and one lumbar puncture after P-gp blockade with tariquidar to measure CSF concentrations of anti-retroviral medications and to measure biomarkers of blood-brain barrier integrity and inflammation in the CSF. HIV-seronegative subjects will receive one lumbar puncture at baseline to measure biomarkers of blood-brain barrier integrity and inflammation in the CSF.
Outcome Measures:
The main outcome measures of the study is brain uptake of [11C]dLop in response to P-gp blockade with tariquidar. We will correct for individual metabolism of tariquidar by measuring the plasma concentration of tariquidar during the P-gp blocked scan.
As a secondary outcome measure, concentrations of anti-retroviral medications in CSF will be measured in HIV seropositive subjects with and without MND. CSF concentrations will be used as a surrogate marker for CNS delivery of anti-retroviral drugs.
Study design
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (14 listed)
- Subject has an acquired mild-to-moderate impairment in cognitive function documented by a score of at least 1 SD below demographically corrected norms on testing of at least two different cognitive domains.
- The cognitive impairment interferes, at least mildly, with activities of daily living, as determined by neuropsychological interview.
- The impairment does not meet DSM-IV criteria for delirium or dementia.
- The impairment is not fully explained by co-morbid conditions.
Key exclusion criteria (12 listed)
- Current Axis I psychiatric illness or severe systemic disease (other than HIV and MND) based on history and physical exam that would make study participation unsafe in the opinion of the investigators.
- Current alcohol use greater than 14 drinks per week for men and 7 drinks per week for women.
- Laboratory tests with clinically significant abnormalities. Normal organ and marrow function are defined as: total leukocyte count greater than or equal to 3000 cells/ul, ANC greater than or equal to 1500 cells/ul, platelet count greater than or equal to 100,000 cells/ul, serum creatinine less than or equal to 2.0 times upper limit of normal, hemoglobin greater than or equal to 9.0 g/dL, serum calcium <12.0 mg/dL, AST/ALT less than or equal to 1.5 times the upper limit of normal, PT 1.5 upper limit of normal.
- EKG finding consistent with ischemic heart disease unless there is documentation of normal cardiac function (e.g., normal stress test or echocardiogram results).
- Previous research radiation exposure (X-rays, PET scans etc.) that, with the study PET scans, would exceed annual research limits.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Brain uptake of [11C]dLop after pharmacological challenge with the P-gp inhibitor tariquidar.
1 secondary outcome
Cerebrospinal fluid concentrations of antiretroviral drugs and inflammatory markers.
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2019.
- Background: PubMed 17591677Kaddoumi A, Choi SU, Kinman L, Whittington D, Tsai CC, Ho RJ, Anderson BD, Unadkat JD. Inhibition of P-glycoprotein activity at the primate blood-brain barrier increases the distribution of nelfinavir into the brain but not into the cerebrospinal fluid. Drug Metab Dispos. 2007 Sep;35(9):1459-62. doi: 10.1124/dmd.107.016220. Epub 2007 Jun 25.
- Background: PubMed 15535131Langford D, Grigorian A, Hurford R, Adame A, Ellis RJ, Hansen L, Masliah E. Altered P-glycoprotein expression in AIDS patients with HIV encephalitis. J Neuropathol Exp Neurol. 2004 Oct;63(10):1038-47. doi: 10.1093/jnen/63.10.1038.
- Background: PubMed 16025095Loscher W, Potschka H. Drug resistance in brain diseases and the role of drug efflux transporters. Nat Rev Neurosci. 2005 Aug;6(8):591-602. doi: 10.1038/nrn1728.
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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.
Robert B Innis, M.D. principal investigator
National Institute of Mental Health (NIMH)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of HIV-Associated Cognitive Motor Complex, run by National Institute of Mental Health (NIMH) 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 14 inclusion and 12 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 16 Dec 2019. 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.
Are results available for this study?
The study was stopped early. 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?
Brain uptake of [11C]dLop after pharmacological challenge with the P-gp inhibitor tariquidar.. 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 NCT01547754, which also lists 3 linked publications.
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 16 Dec 2019.