ACTG Launches Phase 2 Trial Comparing Pramipexole to Escitalopram for Depression and Cognitive Disorders in HIV Patients
核心洞察
ACTG (搜索) has initiated study A5402, a phase 2 randomized trial comparing pramipexole to escitalopram for treating depressive disorders (搜索) with or without mild neurocognitive disorder (搜索) in people living with HIV (搜索).
The study will enroll 186 participants aged 18-70 who are virally suppressed on antiretroviral therapy (搜索) for at least three months.
Combined depressive disorders (搜索) and mild neurocognitive disorder (搜索) affect up to 80 percent of people living with HIV (搜索), representing a two- to four-fold increase compared to the general population.
The AIDS Clinical Trials Group (ACTG (搜索)) has launched study A5402, a phase 2 randomized clinical trial investigating whether pramipexole, a dopamine receptor agonist, offers superior treatment outcomes compared to escitalopram for depressive disorders (搜索) and mild neurocognitive disorder (搜索) (MND) in people living with HIV (搜索). The multi-center, open-label trial represents a significant effort to address neuropsychiatric complications that persist despite successful HIV treatment.
Study Design and Population
A5402 will enroll 186 participants between ages 18 and 70 who have been diagnosed with depressive disorders (搜索) with or without MND. All participants must be on antiretroviral therapy (搜索) (ART) for at least three months and maintain viral suppression. The 24-week study will randomize participants to receive either pramipexole extended release or escitalopram.
The trial is open to ACTG (搜索) clinical research sites with available mental health expertise for consultation and referral, either on-site or within the local institution or community. Study leadership includes Co-Chairs William R. Short, M.D., M.P.H., from the University of Pennsylvania, and Scott Letendre, M.D., from the University of California San Diego, along with Vice Chairs David J. Moore, Ph.D., from UC San Diego, and Shibani Mukerji, M.D., Ph.D., from Massachusetts General Hospital.
Addressing a Critical Unmet Need
The study targets a substantial clinical problem affecting the HIV (搜索) population. Combined depressive disorders (搜索) and MND can affect up to 80 percent of people living with HIV, representing a two- to four-fold increase compared to people without HIV. These conditions persist even when HIV is successfully managed with antiretroviral therapy (搜索).
People with MND demonstrate worse cognitive performance in areas including memory, language, and multitasking compared to those without the condition. When left untreated, these neuropsychiatric complications negatively impact health outcomes by undermining ART adherence, engagement in care, and quality of life.
Novel Therapeutic Approach
The trial evaluates pramipexole, which stimulates dopamine receptors (搜索) in the brain, against escitalopram, a traditional selective serotonin reuptake inhibitor antidepressant. This comparison reflects a shift toward investigating dopaminergic mechanisms in HIV (搜索)-associated neuropsychiatric disorders.
"ACTG (搜索) is eager to gain insights from this study, because we hope that pramipexole will prove to be more effective in treating MND and depressive disorders (搜索) among people living with HIV (搜索) than standard antidepressant therapy," said ACTG Chair Joseph J. Eron, M.D., from the University of North Carolina. "Given the overwhelming prevalence of these conditions among people living with HIV, it is urgent that we identify better approaches so that we can support and help improve their quality of life."
Clinical Significance
The research addresses a critical gap in HIV (搜索) care, where traditional antidepressant approaches may not adequately address the complex neuropsychiatric manifestations seen in this population. Dr. Short emphasized the importance of expanding therapeutic options: "It is critical that we expand tools to address depression and MND, because when they remain untreated, they negatively impact health outcomes by undermining ART adherence, engagement in care, and quality of life."
Funding and Support
The study receives sponsorship from the National Institutes of Health's National Institute of Mental Health and National Institute of Allergy and Infectious Diseases under award numbers UM1 AI068636, UM1 AI107716, and UM1 AI068634. CIPLA provided additional industry support for the trial.
ACTG (搜索), founded in 1987, operates as the world's largest and longest-running clinical trials network focused on HIV (搜索) and other infectious diseases, comprising researchers and staff at 65 locations across four continents.