Effects of Glucocorticoids on Cognition in HIV-infected Women

NCT03237689 | Completed Early Phase 1 DMC FDA Drug

• 2 other identifiers: IRB00145327R01MH113512
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hiv

Outcome Measures

Primary Outcomes (4)

• Hopkins Verbal Learning Test-Revised assesses total learning

  a 12-item list-learning task across 3 trials used to measure total learning. Outcome=total learning across trials (range 0-36). Neuropsychological measures are normed on populations and therefore the clinical significance of a score can be assessed in relation to expected levels of performance.

  change between baseline and 28 days

• Hopkins Verbal Learning Test-Revised assesses verbal memory

  following the 3 learning trials there is a 20-25 minute delay. After the delay, participants are asked to recall as many words as they can from the initial learning list. Outcome=delayed free recall (range 0-12).Neuropsychological measures are normed on populations and therefore the clinical significance of a score can be assessed in relation to expected levels of performance.

  change between baseline and 28 days

• Wechsler Adult Intelligence Scale IV Letter-Number Sequencing assesses working memory condition

  participants hear a series of letters and numbers, and then recite them back in ascending order, with the numbers first and then the letters. Outcome=total correct (range 0-24). Neuropsychological measures are normed on populations and therefore the clinical significance of a score can be assessed in relation to expected levels of performance.

  change between baseline and 28 days

• Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Line Orientation Task assesses visuospatial abilities

  In each of 10 trials, a visual array of 13 lines fans out from a common point of origin. Two target lines are shown beneath each array, and participants must identify the lines within the array that match each of the two target lines. Outcome=Total correct (range=0-20).

  change between baseline and 28 days

Secondary Outcomes (11)

• Trail Making Test Part A assesses processing speed/attention

  change between baseline and 28 days

• Trail Making Test Part B assesses mental flexibility

  change between baseline and 28 days

• Comalli Stroop Test, Trial 1 assesses processing speed/attention

  change between baseline and 28 days

• Comalli Stroop Test, Trial 2 assesses processing speed/attention

  change between baseline and 28 days

• Comalli Stroop Test, Trial 3 assesses behavioral inhibition

  change between baseline and 28 days

Study Arms (2)

Hydrocortisone

EXPERIMENTAL

Low dose hydrocortisone (10mg orally)

Drug: Hydrocortisone

Placebo

PLACEBO COMPARATOR

Placebo tablets, made of starch 1500 powder

Drug: Placebo Oral Tablet

Interventions

Hydrocortisone DRUG

Low dose hydrocortisone (10mg)

Hydrocortisone

Placebo Oral Tablet DRUG

capsules of starch 1500 powder

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Females only;
• HIV-infected;
• Able to give informed consent;
• Able to travel to study site for study participation;
• Age between 18 and 65;
• English as a first language;
• Above-average self-reported levels of perceived stress (\>14 on the perceived stress scale (PSS-10)) and/or current SCID-V diagnosis of mood and/or anxiety disorder;
• Meet criteria for HIV-associated cognitive dysfunction (based on Neurocognitive test battery and instrumental activities of daily living assessment-impairment on only 1 cognitive domain is required)
• Virally suppressed and on combination antiretroviral therapy (Plasma HIV RNA\<1000cp/ml and bring in medications)

You may not qualify if:

• Current use of hormone-based contraceptives (birth control pills or patch);
• Currently pregnant, post-partum or lactating;
• Currently regular use of steroids;
• History of closed head injury resulting in loss of consciousness greater than 1 hour;
• History of schizophrenia or schizoaffective disorder;
• Current untreated hypertension or diabetes\*;
• History of dementia or any other neurologic central nervous system (CNS) or AIDS-defining disorder;
• Positive urine toxicology screen (except marijuana) or breathalyzer and/or any evidence of acute intoxication or withdrawal.
• History of substance abuse/dependence in the past six months.
• Participants who present with a heretofore untreated condition (e.g., hypertension) will be excluded; however, they may be rescreened for eligibility after receiving appropriate treatment for the condition in the course of their standard medical care (at least 6 months).

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21224, United States

Location

Related Links

• Brief Report: Low-Dose Hydrocortisone Has Acute Enhancing Effects on Verbal Learning in HIV-Infected Men
• Elevated stress is associated with prefrontal cortex dysfunction during a verbal memory task in women with HIV
• Prefrontal cortical volume loss is associated with stress-related deficits in verbal learning and memory in HIV-infected women
• Post-traumatic stress is associated with verbal learning, memory, and psychomotor speed in HIV-infected and HIV-uninfected women
• The association of perceived stress and verbal memory is greater in HIV-infected versus HIV-uninfected women

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Hydrocortisone

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Study Officials

• Leah Rubin

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The only entity knowledgeable of randomization is the Johns Hopkins University Investigational Drug Service Pharmacy. They are responsible for randomizing and encapsulating the drug and placebo tablets
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 31, 2017
• First Posted: August 2, 2017
• Study Start: November 20, 2017
• Primary Completion: September 8, 2023
• Study Completion: September 8, 2023
• Last Updated: September 29, 2023

Record last verified: 2023-09

Locations

US (1)