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
  Purpose

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.


Condition Intervention Phase
HIV Associated Neurocognitive Disorder
Drug: Zidovudine
Drug: Sugar pill
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Preliminary Study of Zidovudine Addition for HIV-associated Neurocognitive Disorder

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • 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.


Estimated Enrollment: 46
Study Start Date: October 2013
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: zidovudine
zidovudine 300mg po bid
Drug: Zidovudine
Placebo Comparator: Sugar pill
Lactose free sugar pill
Drug: Sugar pill

  Eligibility

Ages Eligible for Study:   18 Years to 59 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Albert ML Anderson, Principal Investigator, Emory University
ClinicalTrials.gov Identifier: NCT01966094     History of Changes
Other Study ID Numbers: IRB00065880, K23MH095679
Study First Received: September 12, 2013
Last Updated: April 30, 2014
Health Authority: United States: Data and Safety Monitoring Board
United States: Federal Government
United States: Emory Institutional Review Board

Additional relevant MeSH terms:
Zidovudine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on July 23, 2014