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Protocol Details

Screening and Recruitment for HIV-associated Neurocognitive Disorders (HAND) Studies and an Evaluation of HIV-associated Neurocognitive Disorders in Virologically Controlled Patients

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

13-N-0149

Sponsoring Institute

National Institute of Neurological Disorders and Stroke (NINDS)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18
Max Age: N/A

Referral Letter Required

No

Population Exclusion(s)

Children;
Non-English Speaking

Special Instructions

Currently Not Provided

Keywords

Healthy Controls;
HIV-positive;
Neurophyschological Testing;
Thinking and Memory;
Lumbar Drain/Puncture

Recruitment Keyword(s)

None

Condition(s)

HIV Positive

Investigational Drug(s)

None

Investigational Device(s)

None

Intervention(s)

None

Supporting Site

National Institute of Neurological Disorders and Stroke

Background:

- People with human immunodeficiency virus (HIV) can sometimes develop thinking and memory problems. These problems can vary widely, from few symptoms to severe problems with memory and concentration. It initially was thought that good HIV treatment could prevent almost all HIV-related memory problems. However, even people with low HIV viral loads can have these problems. It may be caused by HIV affecting the brain and spinal fluid. It is not yet clear why HIV causes these problems and why they may be worse in some people than others. Researchers want to study people with HIV and healthy volunteers to see how HIV may affect people with only small amounts of the virus in their blood.

Objectives:

- To study thinking and memory problems in individuals with HIV that is otherwise controlled with medications.

Eligibility:

- Individuals between 18 of age or older whose HIV has been controlled with medications for at least 1 year.

- Healthy volunteers between 18 of age or older.

Design:

- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. A neurological test will also be given. Participants will have a baseline imaging study of the brain.

- Within 12 weeks of the first visit, participants will have a second visit. Additional blood samples will be drawn. Another brain imaging study will be performed.

- Within 8 weeks of the second visit, participants will have a third visit to collect more blood samples. They will also provide spinal fluid samples, either as a single visit or a longer procedure.

- After this visit, participants will return every 6 months for up to 5 years. Blood samples will be collected as needed at these visits. Thinking and memory tests and imaging studies may also be given as needed. Spinal fluid may be collected at one visit a year.

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Eligibility

ELIGIBILITY CRITERIA FOR PART I SCREENING STUDY:

INCLUSION CRITERIA:

All Subjects (HIV-infected and HIV-negative Controls):

While different individual HIV neurocognitive studies have specific selection criteria, especially related to HIV viral load and antiretroviral therapy, inclusion criteria for this overarching protocol will be flexible in order to identify the broadest base of potential enrollees possible.

1. Men and women, 18 years of age and older

2. Ability to sign informed consent by the subject

3. At least seventh grade educational level and ability to speak, read, and understand English. Education level will be assessed by subject self-report. Because many of the neuropsychological subtests were validated using United States norms, subjects must be native English speakers or if foreign-born, demonstrate ability to understand the English language at the time of screening protocol consent and neuropsychological testing.

HIV-infected Only:

1. HIV-1 infection, as documented by OraQuick rapid test using venipuncture whole blood, or fingerstick whole blood done at screening; or with HIV-1/HIV-2 Multispot rapid test and Western Blot as determined by NIH Clinical Pathology Laboratory or Leidos Biomedical Research. Monitoring Laboratory.

2. Outside primary medical doctor who provides care

HIV-negative Controls Only:

1.HIV-antibody negative

EXCLUSION CRITERIA:

Screening Study (all participants):

1. Illness or other condition that, in the opinion of the PI, may interfere with study participation at the time of enrollment, including, but not limited to those listed below:

a) CNS infections: this includes but is not limited to Varicella zoster virus (VZV) encephalitis, CNS lymphoma and toxoplasmosis. Subjects who have recovered from effectively treated CNS infections may be considered once they resume baseline daily activities.

b) Non-CNS opportunistic infections: subjects who recovered from or are completing treatment for non-CNS opportunistic infections (OIs) (e.g., Pneumocystis pneumonia, Candida esophagitis, or pulmonary TB) can be enrolled if they have returned to self-reported baseline activity and functional level.

2. Conditions other than HAND associated with cognitive impairment or dementia such as Alzheimer s, Parkinson s disease, head injury with loss of consciousness >30 minutes, untreated sleep apnea with day-time sleepiness, or seizure disorders. Subjects with a history of seizure disorder with no seizure activity that are on a stable, non-sedating anti-seizure regimen for >6 months may be enrolled.

3. Concurrent severe, unstable psychiatric illness that, in the opinion of the investigators, may interfere with study participation and/or data interpretation. Subjects on psychotropic anxiolytic, attention deficit-hyperactivity disorder (ADHD), and other psychiatric medications may be included if clinically stable for >6 months.

4. Concurrent substance abuse that, in the opinion of the investigators may interfere with study participation and/or data interpretation. Active substance abuse includes illegal drug use and/or excessive narcotic or alcohol use as determined by the investigator. Urine drug screen will be performed on all subjects at screening. Use of nicotine containing products will not be an exclusion criterion.

5. Contraindication to MRI/ MRS scanning, including pacemakers or other implanted electrical devices, brain stimulators, some types of dental implants, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), implanted delivery pump, or shrapnel fragments. Patients requiring a low dose oral benzodiazepine for mild to moderate claustrophobia will be allowed to participate. Pregnancy testing will be performed in enrolled female participants 48 hours prior to any MRI.

6. Medications: narcotics, psychiatric, and anti-seizure medications will not be allowed except under certain conditions as noted above. Corticosteroids may be permitted for subjects on stable short-term therapy without CNS disease (i.e., resolving Pneumocystis pneumonia). Participants must be willing not to take the following

medications within 48 hours of neuropsychological testing : sedating antihistamines such as diphenhydramine, zolpidem and other drugs identified by the study team that are associated with altered alertness or impaired memory.

7. Pregnant or Lactating women: Women of childbearing potential must have a negative serum or urine pregnancy test at the time of

screening. Pregnancy testing will also be performed in enrolled female participants prior to any radiation exposure.

ELIGIBILITY CRITERIA FOR PART II NATURAL HISTORY STUDY:

INCLUSION CRITERIA:

Natural History Study (HIV-infected Only):

In addition to the inclusion criteria for the screening study (see above)

1. Plasma HIV-RNA <50 copies/mm(3) or BLD for greater than one year. Patients who experience transitory episodes of an HIV viral load > 50 copies/mm (3) preceded and followed by plasma viremia < 50 copies/mm(3) may be included.

2. At least one year of continuous ART

3. Consent to store blood and tissue

4. Willing to participate on this study for 5 years

Natural History Study (Healthy Controls Only):

1. Men and women, 18 years of age and older

2. Ability to sign informed consent by the subject

3. At least seventh grade educational level and ability to speak, read, and understand English. Education level will be assessed by subject self-report. Because many of the neuropsychological subtests were validated using United States norms, subjects must be native English speakers or if foreign-born, demonstrate ability to understand the English language at the time of screening protocol consent and neuropsychological testing.

4. HIV-antibody negative

PARTICIPANT EXCLUSION CRITERIA:

In addition to the exclusion criteria from the screening protocol (see section above):

1. Inability to refrain from use of anticoagulant/antiplatelet medication, such as dipyridamole (Persantine), clopidogrel (Plavix), dabigatran (Pradaxa), or warfarin (Coumadin) for at least 72 hours prior to invasive procedures (lumbar puncture [LP], lumbar drain).

2. Prior or planned/anticipated exposure to radiation due to clinical care or participation in other research protocols, which would exceed the recommended acceptable annual limit of radiation exposure once accounting for the requirements of the current study.

3. Pregnant or Lactating females are excluded due to exposure to the radioactive compound for PET/CT scans, which may be excreted in the breast milk and could be potentially harmful to breast-fed infants. There is also exposure to radiation from the CT part of the PET/CT scan and the lumbar puncture if done under fluoroscopy. Women of childbearing potention must have a negative serum or urine pregnancy 48 hours prior to any radiation exposure.

EXCLUSION OF PREGNANT OR LACTATING WOMEN:

The study requires exposure to high magnetic fields and irradiation, which could pose a risk to the fetus. Futher, we will be studying growth factors and inflammatory mediators in blood and CSF all of which will be affected by the state of pregnancy and then post partum state. Women who are lactating are excluded because the study may result in transfer of radioactive tracer in breast milk.

EXCLUSION OF CHILDREN::

Subjects younger than 18 years of age are excluded because the developing brain is not within the scope of this study.

Department of Defense MRI-only Inclusion/Exclusion Criteria:

Due to the nature of the military population, the ALLHANDS DOD protocol has some notable differences in the inclusion/exclusion criteria. Note that only HIV+ participants will come from the DOD.

1. No ART use or HIV viral load level requirement.

2. Outside primary medical doctor requirement not included as subjects are military beneficiaries who have primary medical care

3. Illicit drug testing will not be performed for this study to avoid risk of inadvertent identification and disclosure of a positive result. Prior studies have shown drug use to be very low in this population.

4. Head injury with loss of consciousness >30 minutes will be noted, but not an exclusion criterion.

5. Untreated sleep apnea with daytime sleepiness will be noted, but not an exclusion criterion Sleep disorders were found to be prevalent among this population.


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Citations:

Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M, Clifford DB, Cinque P, Epstein LG, Goodkin K, Gisslen M, Grant I, Heaton RK, Joseph J, Marder K, Marra CM, McArthur JC, Nunn M, Price RW, Pulliam L, Robertson KR, Sacktor N, Valcour V, Wojna VE. Updated research nosology for HIV-associated neurocognitive disorders. Neurology. 2007 Oct 30;69(18):1789-99. Epub 2007 Oct 3.

McArthur JC. HIV dementia: an evolving disease. J Neuroimmunol. 2004 Dec;157(1-2):3-10.

Sacktor N, McDermott MP, Marder K, Schifitto G, Selnes OA, McArthur JC, Stern Y, Albert S, Palumbo D, Kieburtz K, De Marcaida JA, Cohen B, Epstein L. HIV-associated cognitive impairment before and after the advent of combination therapy. J Neurovirol. 2002 Apr;8(2):136-42.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Avindra Nath, M.D.
National Institute of Neurological Disorders and Stroke (NINDS)
BG 10 RM 7C103
10 CENTER DR
BETHESDA MD 20814
(301) 496-1561
natha@mail.nih.gov

Amanda M. Wiebold
National Institute of Neurological Disorders and Stroke (NINDS)
National Institutes of Health
Building 10
Room 7C107
10 Center Drive
Bethesda, Maryland 20892
(301) 594-5194
amanda.wiebold@nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: 1-866-411-1010
PRPL@cc.nih.gov

Clinical Trials Number:

NCT01875588

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