Trial record 9 of 31 for:    " February 15, 2012":" March 16, 2012"[FIRST-RECEIVED-DATE]AND HIV[CONDITION]

Mild Neurocognitive Disorder in HIV Infection of the Brain

This study has been terminated.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01547754
First received: March 6, 2012
Last updated: August 26, 2014
Last verified: August 2014
  Purpose

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.

Condition
HIV-Associated Cognitive Motor Complex

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Inflammation and Function of P-gp in HIV Infection of Brain

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Brain uptake of [11C]dLop after pharmacological challenge with the P-gp inhibitor tariquidar.

Secondary Outcome Measures:
  • Cerebrospinal fluid concentrations of antiretroviral drugs and inflammatory markers.

Enrollment: 8
Study Start Date: January 2012
Estimated Study Completion Date: August 2014
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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

    1. Subjects must be between 18 and 60 years of age.
    2. Capable of providing informed consent.
    3. Ambulatory at initial visit.
    4. Speak English fluently
    5. For HIV seropositive subjects:

      1. Confirmation of HIV antibody status by ELISA and Western Blot
      2. Documented HIV-infection for at least one year
      3. On a stable antiretroviral regimen that includes a protease inhibitor for at least 3 months and have a viral load < 400 copies/mL.
      4. Have a primary care physician.

Specific inclusion criteria for mild neurocognitive disorder are as follows:

  1. 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.
  2. The cognitive impairment interferes, at least mildly, with activities of daily living, as determined by neuropsychological interview.
  3. The impairment does not meet DSM-IV criteria for delirium or dementia.
  4. The impairment is not fully explained by co-morbid conditions.

EXCLUSION CRITERIA:

  1. 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.
  2. Current alcohol use greater than 14 drinks per week for men and 7 drinks per week for women.
  3. 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.
  4. EKG finding consistent with ischemic heart disease unless there is documentation of normal cardiac function (e.g., normal stress test or echocardiogram results).
  5. Previous research radiation exposure (X-rays, PET scans etc.) that, with the study PET scans, would exceed annual research limits.
  6. Pregnancy or breast feeding.
  7. Evidence of brain disease such as stroke, tumor, epilepsy, traumatic brain injury, or any neurodegenerative disease on history or on screening MRI.
  8. Inability to lay on his/her back for long periods, severe claustrophobia, pacemaker, or other contraindication for MRI.
  9. More than moderate hypertension, defined as blood pressure greater than or equal to 160/95 at the time of screening.
  10. Current use of illicit drugs based on positive result on urine screen for illicit drugs at the time of screening.
  11. 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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01547754

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Robert B Innis, M.D. National Institute of Mental Health (NIMH)
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT01547754     History of Changes
Other Study ID Numbers: 120059, 12-M-0059
Study First Received: March 6, 2012
Last Updated: August 26, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Neuroinflammation
HIV
Positron Emission Tomograhy (PET)
Mild Neurocognitive Disorder
P-Glycoprotein
Mild Cognitive Disorder
Healthy Volunteer
HV

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
AIDS Dementia Complex
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on September 16, 2014