Pramipexole Versus Escitalopram to Treat Major Depressive Disorder (MDD) and Comorbid MDD With Mild Neurocognitive Disorder (MND) in Persons With HIV

Phase 2

Not yet recruiting

• Conditions: Major Depressive Disorder; Mild Neurocognitive Disorder; HIV
• Interventions: Drug: Pramipexole ER; Drug: Escitalopram

• Registration Number: NCT06705478
• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary

A phase II, randomized, open-label, two-arm clinical trial evaluating the safety and efficacy of pramipexole extended release (ER) versus escitalopram for the treatment of major depressive disorder (MDD) and comorbid MDD with mild neurocognitive disorder (MND) in persons with HIV (PWH). Participants will be assessed comprehensively and briefly at intercurrent visits to monitor for toxicity, response to therapy, and to assess for dose changes.

An optional sub-study to evaluate treatment impact on the cerebrospinal fluid (CSF) profile will be conducted in a subset of 36 participants.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-11-22
• Study First Submitted QC: 2024-11-22
• Study First Posted: 2024-11-26
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-10
• Last Update Posted: 2025-02-11
• Study Start: 2025-04-24
• Primary Completion: 2026-12-02
• Study Completion: 2026-12-02

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 186

Inclusion Criteria

• Documented HIV-1 infection.
• Diagnosis of MDD.
• On current ART regimen for at least 90 days prior to study entry with no interruption in treatment greater than 7 consecutive days.
• No plans to change ART while on study.
• Plasma HIV-1 RNA levels of less than 200 copies/mL obtained within 90 days prior to enrollment.
• Study candidates previously treated for depression are eligible provided the study candidate's last dose of antidepressant taken is at least 4 weeks prior to study entry, with the exception of fluoxetine, which the last dose taken must have been at least 8 weeks prior to study entry.
• Laboratory values obtained within 30 days prior to study entry that meet protocol criteria as determined by the site investigator of record.
• Study candidates of child-bearing potential must have a negative serum or urine pregnancy test performed at screening and within 2 days prior to study entry.
• Study candidates of child-bearing potential who are participating in sexual activity that could lead to pregnancy must agree to use at least one highly effective method for contraception.

Exclusion Criteria

• Active suicidality, and/or severe MDD, psychotic disorders, manic or hypomanic symptoms occurring in the context of bipolar disorder type I or II, or cyclothymic disorder, or another current Axis I diagnosis judged by the investigator to interfere with the trial.
• Study candidate self-report of depressive symptoms that have persisted for over 50 percent of waking hours and for over 50 percent of days over the 24 months prior to study entry.
• Severe, active alcohol or substance use disorder by DSM-5-TR criteria in the 6 months prior to study entry.
• Active alcohol or substance use judged by the investigator to interfere with the trial.
• Any acute infection within 14 days prior to study entry.
• Acute or serious illness requiring systemic treatment and/or hospitalization within 90 days prior to study entry.
• Active coronary artery disease (CAD) or myocardial infarction (MI) within 180 days prior to study entry.
• Presence of rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus (SLE), dermatomyositis, ulcerative colitis, Crohn's disease, or other chronic inflammatory conditions.
• Immune reconstitution inflammatory syndrome (IRIS) or a history of IRIS within 180 days prior to study entry.
• Unstable or advanced liver disease.
• Receipt of medications judged by the site investigator to significantly influence depression or neurocognitive function within 30 days prior to study entry.
• Non-HIV-associated neurological disorder comorbidity.
• Diagnosis of epilepsy with antiepileptic drug treatment.
• Untreated HCV infection and HCV viremia.
• Current CNS malignant tumor or CNS opportunistic infection (OI).
• Current systemic malignant tumor or of a current systemic AIDS-defining OI.
• History of completed treatment of CNS or systemic malignant tumor within the 5 years prior to study entry.
• History of completed treatment of CNS OI within the 5 years prior to study entry.
• Documented history of completed treatment of systemic AIDS-defining OI, as well as Mycobacterium Tuberculosis Infection, within the 180 days prior to study entry.
• New diagnosis of syphilis or treatment for syphilis within the 180 days prior to study entry.
• History of neurosyphilis.
• Severe chronic obstructive pulmonary disease.
• Congestive heart failure (CHF).
• Use of systemic steroids daily (except testosterone).
• Diseases that cause a known bleeding diathesis.
• Immunostimulant therapies and trials of non-FDA-approved ARV medications within 30 days prior to study entry.
• Immunosuppressive medications if judged by the investigator to affect study outcomes.
• Currently pregnant, planning to become pregnant during the study period, or currently breastfeeding.
• Known allergy/sensitivity or any hypersensitivity to the study drugs or their formulations.
• Study candidates on prohibited medications at the time of screening will be excluded from study participation.

Inclusion Criteria for Participants at US Sites Who Consent to the Lumbar Puncture (LP) Procedure:

• Non-focal neurological examination. Study candidates with focal findings should have expert assessment for mass effect prior to the LP.
• Laboratory values that meet LP protocol criteria as determined by the site investigator.
• No history of a positive syphilis testing per local testing algorithms or clinical documentation of prior syphilis treatment.

Exclusion Criteria for Participants at US Sites who Consent to the LP Procedure:

• Current use of anti-coagulants.
• Known presence of intracerebral mass or lesion that is judged to affect the safety of an LP.
• Known presence of an active CNS infection that could alter CNS/CSF inflammatory measures.
• Known allergy to lidocaine.
• Individuals who are unable to safely tolerate an LP due to physical limitation or condition.
• Body mass index (BMI) greater than 40 kg/m^2.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1: Pramipexole ER	Pramipexole ER	-
Arm 2: Escitalopram	Escitalopram	-

Primary Outcome Measures

Name	Time	Method
Change in Beck Depression Inventory-II (BDI-II/BDI-2) total score defined as the sum of all symptom scores	Baseline, Week 24
Occurrence of Grade ≥3 Adverse Events (AEs) or Grade ≥2 neuropsychiatric AEs related to study treatment	From study treatment administration through Week 24
Occurrence of Grade ≥2 neuropsychiatric AEs related to study treatment	From study treatment administration through Week 24

Secondary Outcome Measures

Name	Time	Method
Change in major depressive disorder (MDD) caseness, defined as the number of symptoms present from 0 to 9, of the symptoms of major depressive disorder	Baseline, Week 24
Complete remission of the major depressive episode defined as a score of 0 on all of the 9 symptoms	Baseline, Week 24
Change in the MOS-HIV cognitive functioning subscale score defined by the MOS-HIV Users Manual	Baseline, Week 24
Change in neuropsychological (NP) z-score as assessed through 4 composite domain scores	Baseline, Week 24	Each domain score is calculated as the average of the z-scores from the tests within the domain: * Outcome Domain 1: Cognitive Efficiency (Color Trails 1 and 2); * Outcome Domain 2: Verbal Learning and Memory (HVLT-R Learning Trials 1-3 Total and HVLT-R Delayed Recall); * Outcome Domain 3: Motor Skills (Grooved Pegboard, Non-dominant hand); * Outcome Domain 4: Language (Category Fluency Test \[Animals\])
Change in the medical outcomes study (MOS)-HIV mental health functioning summary score defined by the MOS-HIV Users Manual	Baseline, Week 24
Occurrence of Grade ≥2 neuropsychiatric AEs (regardless of judged relationship to study treatment)	From study treatment administration through Week 24
Occurrence of Grade ≥3 AEs or Grade ≥2 neuropsychiatric AEs (regardless of judged relationship to study treatment)	From study treatment administration through Week 24
Number of participants with plasma HIV-1 RNA less than 50 copies/mL	Week 24

Trial Locations

Locations (39)

Alabama CRS; 🇺🇸 Birmingham, Alabama, United States

University of California, Los Angeles CARE Center CRS; 🇺🇸 Los Angeles, California, United States

UCSD Antiviral Research Center CRS; 🇺🇸 San Diego, California, United States

University of California, San Francisco HIV/AIDS CRS; 🇺🇸 San Francisco, California, United States

Harbor University of California, Los Angeles Center CRS; 🇺🇸 Torrance, California, United States

University of Colorado Hospital CRS; 🇺🇸 Aurora, Colorado, United States

Whitman-Walker Institute, Inc. CRS; 🇺🇸 Washington, District of Columbia, United States

The Ponce de Leon Center CRS; 🇺🇸 Atlanta, Georgia, United States

Northwestern University CRS; 🇺🇸 Chicago, Illinois, United States

Massachusetts General Hospital CRS (MGH CRS); 🇺🇸 Boston, Massachusetts, United States

Washington University Therapeutics (WT) CRS; 🇺🇸 Saint Louis, Missouri, United States

Weill Cornell Chelsea CRS; 🇺🇸 New York, New York, United States

Columbia Physicians & Surgeons (P&S) CRS; 🇺🇸 New York, New York, United States

Weill Cornell Uptown CRS; 🇺🇸 New York, New York, United States

University of Rochester Adult HIV Therapeutic Strategies Network CRS; 🇺🇸 Rochester, New York, United States

Chapel Hill CRS; 🇺🇸 Chapel Hill, North Carolina, United States

Greensboro CRS; 🇺🇸 Greensboro, North Carolina, United States

Cincinnati CRS; 🇺🇸 Cincinnati, Ohio, United States

Case CRS; 🇺🇸 Cleveland, Ohio, United States

Ohio State University CRS; 🇺🇸 Columbus, Ohio, United States

Penn Therapeutics CRS; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Pittsburgh CRS; 🇺🇸 Pittsburgh, Pennsylvania, United States

Vanderbilt Therapeutics (VT) CRS; 🇺🇸 Nashville, Tennessee, United States

Houston Advancing Research Team CRS; 🇺🇸 Houston, Texas, United States

Gaborone CRS; 🇧🇼 Gaborone, Botswana

Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS; 🇧🇷 Rio De Janeiro, Brazil

Byramjee Jeejeebhoy Medical College (BJMC) CRS; 🇮🇳 Pune, Maharashtra, India

Moi University Clinical Research Center (MUCRC) CRS; 🇰🇪 Eldoret, Rift Valley, Kenya

Kenya Medical Research Institute/Walter Reed Project Clinical Research Center (KEMRI/WRP) CRS; 🇰🇪 Kericho, Rift Valley, Kenya

Blantyre CRS; 🇲🇼 Blantyre, Malawi

Nutrición-Mexico CRS; 🇲🇽 Mexico City, Tlalpan, Mexico

Barranco CRS; 🇵🇪 Lima, Peru

De La Salle Medical and Health Sciences Institute - Angelo King Medical Research Center (DLSMHSI-AKMRC); 🇵🇭 Dasmariñas, Cavite, Philippines

Durban International CRS; 🇿🇦 Mount Edgecombe, South Africa

Thai Red Cross AIDS Research Centre (TRC-ARC) CRS; 🇹🇭 Pathum Wan, Bangkok, Thailand

Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS; 🇹🇭 Chiang Mai, Thailand

Joint Clinical Research Centre (JCRC)/Kampala CRS; 🇺🇬 Kampala, Uganda

Hanoi Medical University (HMU); 🇻🇳 Hanoi, Vietnam

Milton Park CRS; 🇿🇼 Milton Park, Harare, Zimbabwe