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Preliminary Study of Zidovudine Addition for HIV-associated Neurocognitive Disorder

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified April 2014 by Emory University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Albert ML Anderson, Emory University
ClinicalTrials.gov Identifier:
NCT01966094
First received: September 12, 2013
Last updated: April 30, 2014
Last verified: April 2014

September 12, 2013
April 30, 2014
October 2013
October 2017   (final data collection date for primary outcome measure)
Difference in neurocognition change over 48 weeks as measured by a summary score (NPZ-8) that reflects an 8 test neurocognitive battery. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
NPZ-8 scores will be determined at each of the four visits (baseline, 12 weeks, 24 weeks, and 48 weeks). The NPZ-8 score equals the subject score minus the mean age adjusted score divided by the standard deviation of the second score.
Same as current
Complete list of historical versions of study NCT01966094 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
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Preliminary Study of Zidovudine Addition for HIV-associated Neurocognitive Disorder
Preliminary Study of Zidovudine Addition for HIV-associated Neurocognitive Disorder

It is estimated that over 1 million people in the United States have HIV infection. While HIV is treatable, there are still high rates of HIV-associated neurocognitive disorder (HAND). HAND is defined by low scores on memory testing. To meet the criteria for HAND, an HIV-infected individual has to have a low score on at least two different memory tests. It is estimated that 20-50% of people living with HIV have HAND. It is therefore still a common problem. While individuals with HAND typically improve on antiretroviral therapy for HIV, often this improvement is incomplete. Also, there are over 20 antiretroviral medications approved for HIV in the US. It is not clear if the specific choice of antiretroviral medication makes a difference in the improvement of HAND.

In this study, the investigators will examine the addition of zidovudine or placebo to a standard medication regimen for individuals with HAND. Zidovudine (typically referred to as AZT) was the first medication approved for the treatment of HIV. It has been approved for over 25 years. Early studies of AZT showed that it was beneficial for individuals with HAND. However, these early studies typically used AZT alone without other antiretrovirals. As a result, the clinical benefit of AZT was time limited due to the emergence of HIV resistance to the drug. Since then, new therapies have been approved for HIV and current guidelines state that 3 drug regimens be used to avoid resistance. The question remains if the addition of AZT into a standard regimen would allow for greater improvement in subjects with HAND.

To address this question, the investigators have designed a small preliminary study in which subjects with HAND who have never been on treatment for HIV are given a standard of care HIV regimen plus either AZT or placebo. The standard of care regimen (raltegravir/tenofovir/emtricitabine) is one of the first choice HIV regimens in the US. The investigators will enroll a maximum of 46 subjects (23 subjects in each arm). Subjects will also be followed by their primary HIV medical provider. For the study, subjects will be followed for 48 weeks. There are three followup visits: 12 weeks, 24 weeks, and 48 weeks. Memory testing will be performed at baseline and each followup visit. Blood will also be taken at baseline and the three followup visits to measure changes in inflammation. A lumbar puncture will be performed at baseline and at 24 weeks to measure changes in inflammation and amount of HIV virus in the spinal fluid. There is also an optional lumbar puncture at the last study visit of 48 weeks.

AZT is typically well tolerated, but side effects such as nausea and headache can occur. The most common side effect of lumbar puncture is headache. Subjects will be monitored closely for side effects at each study visit as well as a once monthly phone call from the study coordinator.

Due to the small nature of the study, the investigators do not expect to find clinically meaningful memory differences between the two groups. Instead, the investigators will be looking for small changes in memory testing as well as changes in inflammation in the blood and spinal fluid over the course of the study. If these small changes are found, the results would be used to create a study looking at AZT addition in a larger group of individuals with HAND.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
HIV Associated Neurocognitive Disorder
  • Drug: Zidovudine
  • Drug: Sugar pill
  • Experimental: zidovudine
    zidovudine 300mg po bid
    Intervention: Drug: Zidovudine
  • Placebo Comparator: Sugar pill
    Lactose free sugar pill
    Intervention: Drug: Sugar pill
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
46
June 2018
October 2017   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Confirmed HIV infection (HAART naïve), subjects 18 to 59 years of age
  2. Subject meets criteria for HAND by screening neurocognitive tests
  3. Negative serum cryptococcal antigen if CD4+ T-cell count <200 cells/microliter, normal serum thyroid stimulating hormone level, negative serum rapid plasma reagin (RPR) (Can have positive RPR ≤1:4 if treated for syphilis by CDC guidelines at least 6 months prior to enrollment, had no signs/symptoms of neurosyphilis, and RPR titer decreased at least 4-fold by 6 months after treatment).

Exclusion Criteria:

  1. Ongoing heavy alcohol use (more than 2 drinks per day) or ongoing illicit drug use
  2. Schizophrenia or other psychotic disorder, bipolar disorder, or uncontrolled depression as reported by the subject or medical provider.
  3. Neoplasm of the CNS OR CNS infection in the last 6 months
  4. Creatinine clearance <60 ml/minute as estimated by the Cockcroft-Gault equation
  5. Hemoglobin <8 milligrams/deciliter
  6. Resistance mutations on baseline HIV genotype (standard of care) affecting the study regimen
  7. Pregnancy or incarceration
Both
18 Years to 59 Years
No
Not Provided
 
NCT01966094
IRB00065880, K23MH095679
Yes
Albert ML Anderson, Emory University
Emory University
National Institute of Mental Health (NIMH)
Not Provided
Emory University
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP