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

May 18, 2026 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

An Open-Label, Randomized Controlled Trial of Pramipexole Versus Escitalopram to Treat Major Depressive Disorder (MDD) and Comorbid MDD With Mild Neurocognitive Disorder (MND) in Persons With HIV

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

186

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Botswana
      • Gaborone, Botswana
        • Not yet recruiting
        • Gaborone CRS
        • Contact:
  • Brazil
      • Rio de Janeiro, Brazil, 21040-900
        • Not yet recruiting
        • Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS
        • Contact:
    • Rio Grande do Sul
      • Porto Alegre, Rio Grande do Sul, Brazil, 91350-180
        • Not yet recruiting
        • Instituto de Pesquisas em AIDS do Rio Grande do Sul - IPARGS CRS
        • Contact:
  • India
    • Maharashtra
      • Pune, Maharashtra, India, 411001
        • Not yet recruiting
        • Byramjee Jeejeebhoy Medical College (BJMC) CRS
        • Contact:
  • Kenya
    • Rift Valley
      • Eldoret, Rift Valley, Kenya, 30100
        • Not yet recruiting
        • Moi University Clinical Research Center (MUCRC) CRS
        • Contact:
      • Kericho, Rift Valley, Kenya, 20200
        • Not yet recruiting
        • Kenya Medical Research Institute/Walter Reed Project Clinical Research Center (KEMRI/WRP) CRS
        • Contact:
  • Malawi
      • Blantyre, Malawi, 265
        • Not yet recruiting
        • Blantyre CRS
        • Contact:
          • Dumisile Huwa
          • Phone Number: 265-811885
          • Email: dhuwa@jhp.mw
  • Mexico
    • Tlalpan
      • Mexico City, Tlalpan, Mexico, 14080
        • Not yet recruiting
        • Nutrición-Mexico CRS
        • Contact:
  • Peru
      • Lima, Peru, 15063
        • Not yet recruiting
        • Barranco CRS
        • Contact:
  • Philippines
    • Cavite
      • Dasmariñas, Cavite, Philippines, 4114
        • Not yet recruiting
        • De La Salle Medical and Health Sciences Institute - Angelo King Medical Research Center (DLSMHSI-AKMRC)
        • Contact:
  • South Africa
      • Mount Edgecombe, South Africa, 4302
  • Thailand
      • Chiang Mai, Thailand, 50200
        • Not yet recruiting
        • Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS
        • Contact:
    • Bangkok
      • Pathum Wan, Bangkok, Thailand, 10330
        • Not yet recruiting
        • Thai Red Cross AIDS Research Centre (TRC-ARC) CRS
        • Contact:
  • Uganda
      • Kampala, Uganda
        • Not yet recruiting
        • Joint Clinical Research Centre (JCRC)/Kampala CRS
        • Contact:
          • D. Sandra Rwambuya
          • Phone Number: 256-417-723-000
          • Email: dxr23@case.edu
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35222
    • California
      • Los Angeles, California, United States, 90035
        • Recruiting
        • University of California, Los Angeles CARE Center CRS
        • Contact:
      • San Diego, California, United States, 92103
        • Recruiting
        • UCSD Antiviral Research Center CRS
        • Contact:
      • San Francisco, California, United States, 94110
        • Recruiting
        • University of California, San Francisco HIV/AIDS CRS
        • Contact:
      • Torrance, California, United States, 90502
        • Recruiting
        • Harbor University of California, Los Angeles Center CRS
        • Contact:
    • Colorado
      • Aurora, Colorado, United States, 80045
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20009
    • Georgia
      • Atlanta, Georgia, United States, 30308-2012
        • Recruiting
        • The Ponce de Leon Center CRS
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Not yet recruiting
        • Northwestern University CRS
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital CRS (MGH CRS)
        • Contact:
    • Missouri
      • St Louis, Missouri, United States, 63110-1010
        • Recruiting
        • Washington University Therapeutics (WT) CRS
        • Contact:
    • New Jersey
      • Newark, New Jersey, United States, 07103
        • Recruiting
        • New Jersey Medical School Clinical Research Center CRS (Site ID 31786)
        • Contact:
    • New York
      • New York, New York, United States, 10065
        • Not yet recruiting
        • Weill Cornell Uptown CRS
        • Contact:
      • New York, New York, United States, 10032
        • Not yet recruiting
        • Columbia Physicians & Surgeons (P&S) CRS
        • Contact:
      • New York, New York, United States, 10010
        • Not yet recruiting
        • Weill Cornell Chelsea CRS
        • Contact:
      • Rochester, New York, United States, 14642
        • Not yet recruiting
        • University of Rochester Adult HIV Therapeutic Strategies Network CRS
        • Contact:
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599-7215
      • Greensboro, North Carolina, United States, 27401-1020
    • Ohio
      • Cincinnati, Ohio, United States, 45267-0405
        • Recruiting
        • Cincinnati CRS
        • Contact:
      • Cleveland, Ohio, United States, 44106
      • Columbus, Ohio, United States, 43210
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
      • Pittsburgh, Pennsylvania, United States, 15213
        • Recruiting
        • University of Pittsburgh CRS
        • Contact:
    • Tennessee
      • Nashville, Tennessee, United States, 37204
        • Not yet recruiting
        • Vanderbilt Therapeutics (VT) CRS
        • Contact:
    • Texas
      • Houston, Texas, United States, 77030
        • Not yet recruiting
        • Houston Advancing Research Team CRS
        • Contact:
  • Vietnam
      • Hanoi, Vietnam, 10000
        • Not yet recruiting
        • Hanoi Medical University (HMU)
        • Contact:
  • Zimbabwe
    • Harare
      • Milton Park, Harare, Zimbabwe
        • Not yet recruiting
        • Milton Park CRS
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm 1: Pramipexole ER
Drug: Pramipexole ER
Tablets self-administered orally
Experimental: Arm 2: Escitalopram
Drug: Escitalopram
Tablets self-administered orally

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: Baseline, Week 24
Baseline, Week 24
Complete remission of the major depressive episode defined as a score of 0 on all of the 9 symptoms
Time Frame: Baseline, Week 24
Baseline, Week 24
Change in neuropsychological (NP) z-score as assessed through 4 composite domain scores
Time Frame: 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])
Baseline, Week 24
Change in the medical outcomes study (MOS)-HIV mental health functioning summary score defined by the MOS-HIV Users Manual
Time Frame: Baseline, Week 24
Baseline, Week 24
Change in the MOS-HIV cognitive functioning subscale score defined by the MOS-HIV Users Manual
Time Frame: Baseline, Week 24
Baseline, Week 24
Occurrence of Grade ≥3 AEs or Grade ≥2 neuropsychiatric AEs (regardless of judged relationship to study treatment)
Time Frame: From study treatment administration through Week 24
From study treatment administration through Week 24
Occurrence of Grade ≥2 neuropsychiatric AEs (regardless of judged relationship to study treatment)
Time Frame: From study treatment administration through Week 24
From study treatment administration through Week 24
Number of participants with plasma HIV-1 RNA less than 50 copies/mL
Time Frame: Week 24
Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Cipla Ltd.

Investigators

  • Study Chair: William R Short, MD, University of Pennsylvania
  • Study Chair: Scott Letendre, MD, University of California, San Diego

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 17, 2026

Primary Completion (Estimated)

December 2, 2026

Study Completion (Estimated)

December 2, 2026

Study Registration Dates

First Submitted

November 22, 2024

First Submitted That Met QC Criteria

November 22, 2024

First Posted (Actual)

November 26, 2024

Study Record Updates

Last Update Posted (Actual)

May 19, 2026

Last Update Submitted That Met QC Criteria

May 18, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • A5402

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participant data that underlie results in publication, after deidentification.

IPD Sharing Time Frame

Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH.

IPD Sharing Access Criteria

  • With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group.
  • For what types of analyses? To achieve aims in the proposal approved by the AIDS Clinical Trials Group.
  • By what mechanism will data be made available? Researchers may submit a request for access to data using the AIDS Clinical Trials Group "Data Request" form at: https://actgnetwork.org/submit-a-proposal/. Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on HIV

Clinical Trials on Pramipexole ER

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Guinea

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe