Effects of Glucocorticoids on Cognition in HIV-infected Women
Condition: Hiv
Study type: Interventional
Phase: Early Phase 1

Summary: 
      Despite treatment with antiretroviral therapy, women living with HIV continue to experience
      cognitive impairment. Psychological risk factors, including stress, impair cognition more in
      HIV-infected women than HIV-uninfected women. This study plans to examine a novel
      intervention for cognitive dysfunction that targets the mechanisms by which stress negatively
      affects cognitive functioning.
    

Detailed description: 
      The overall aim of this study is to contribute important foundational knowledge of the
      utility of targeting neuroinflammation and the hypothalamic-pituitary-adrenal (HPA) axis to
      improve cognition in HIV and will provide key clinical insights into the mechanisms
      underlying any cognitive benefit. The investigators are conducting a single-dose study of low
      dose hydrocortisone (LDH) followed by a 4-week study of daily LDH as a probe of the
      mechanisms of neuroinflammation including myeloid-lineage cells and the HPA axis in
      HIV-infected (HIV+) women demonstrating cognitive dysfunction and reporting high levels of
      stress, trauma history, and mental health risk factors which commonly occur in this
      population. The use of a pharmacological challenge may aid in the identification of: 1) a
      putative biomarker of stress- and psychiatric disorder-related neurocognitive complications
      in HIV-infected women and/or 2) an adjunctive, cost-effective therapy for the treatment of
      cognitive deficits in HIV

      The design is a two-phase study of HIV+ women who: 1) first participate in a double-blind,
      placebo-controlled cross-over study of a single, low dose (10 mg) of hydrocortisone versus
      placebo on cognition; and 2) then participate in a mechanistic, randomized, double-blind,
      placebo controlled trial of daily LDH for 4 weeks on cognition and side effects. The clinical
      trial will include 100 virally suppressed HIV+ women who show elevated stress and cognitive
      impairment and who represent the range of psychological risk factors characteristic of this
      population. Next, to understand the mechanism and broader clinical significance of LDH on
      cognition, investigators will conduct a 4-week randomized study of the effects of daily
      treatment with LDH versus placebo on cognition in HIV+ women (targeted n=80).

      Women meeting enrollment criteria will complete three cognitive assessments. The first and
      second assessments will be embedded in the double-blind, placebo-controlled, cross-over study
      of a single administration of LDH versus placebo (targeted n=100). Investigators will measure
      cognitive performance 30 minutes and 4 hours post-dosing, because an emerging literature
      shows that the cognitive effects of LDH depends on timing of the assessment post-dosing. The
      30-minute assessment addresses how the maximal cortisol levels following LDH affect
      cognition. This immediate assessment is standard in studies of stress and cognition and
      allows for comparisons with the broader literature. More novel and clinically important is
      the 4-hour assessment which occurs post-peak, when cortisol levels are more steady state and
      typical of the broader daily cortisol profile following LDH. The third assessment will take
      place after 4 weeks of treatment with LDH or placebo. That assessment addresses the clinical
      significance and safety of longer-term LDH treatment. Lastly, the investigators will explore
      glucocorticoids and inflammation and immune activation as mechanisms by which LDH might
      affect cognition.

      Objective 1 To examine immediate and delayed effects of a single administration of LDH on
      cognition in HIV+ women.

      Objective 2 To examine the effects of a 4-week course of daily LDH on cognition in HIV+
      women.

      Objective 3 To investigate potential mechanisms of LDH effects on cognition in HIV+ women.
    

Intervention name(s): Hydrocortisone; Placebo Oral Tablet
Intervention type(s): Drug; Drug
Intervention description(s): Low dose hydrocortisone (10mg); capsules of starch 1500 powder
Intervention MeSH terms: Hydrocortisone
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The design is a two-phase study of HIV+ women who: 1) first participate in a double-blind, placebo-controlled cross-over study of a single, low dose (10 mg) of hydrocortisone versus placebo on cognition; and 2) then participate in a mechanistic, randomized, double-blind, placebo controlled trial of daily LDH for 4 weeks on cognition and side effects.
Below includes the number of arms for the second study phase and is the phase of the study being considered a Phase 0 clinical trial. All information to follow will pertain to this phase of the study.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science