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

NCT06705478 | Recruiting Phase 2 FDA Drug

• 1 other identifier: A5402
• Study Type: interventional
• Target: 186
• Locations: 14 countries
• Sites: 40

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.

Conditions

Major Depressive Disorder; Mild Neurocognitive Disorder; HIV

Keywords

Comorbid MND

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (8)

• 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 neuropsychological (NP) z-score as assessed through 4 composite domain scores

  Baseline, Week 24

• Change in the medical outcomes study (MOS)-HIV mental health functioning summary score defined by the MOS-HIV Users Manual

  Baseline, Week 24

• Change in the MOS-HIV cognitive functioning subscale score defined by the MOS-HIV Users Manual

  Baseline, Week 24

Study Arms (2)

Arm 1: Pramipexole ER

EXPERIMENTAL

Drug: Pramipexole ER

Arm 2: Escitalopram

EXPERIMENTAL

Drug: Escitalopram

Interventions

Pramipexole ER DRUG

Tablets self-administered orally

Arm 1: Pramipexole ER

Escitalopram DRUG

Tablets self-administered orally

Arm 2: Escitalopram

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Cipla Ltd.: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (40)

Alabama CRS

Birmingham, Alabama, 35222, United States

RECRUITING

University of California, Los Angeles CARE Center CRS

Los Angeles, California, 90035, United States

RECRUITING

UCSD Antiviral Research Center CRS

San Diego, California, 92103, United States

RECRUITING

University of California, San Francisco HIV/AIDS CRS

San Francisco, California, 94110, United States

RECRUITING

Harbor University of California, Los Angeles Center CRS

Torrance, California, 90502, United States

RECRUITING

University of Colorado Hospital CRS

Aurora, Colorado, 80045, United States

RECRUITING

Whitman-Walker Institute, Inc. CRS

Washington D.C., District of Columbia, 20009, United States

RECRUITING

The Ponce de Leon Center CRS

Atlanta, Georgia, 30308-2012, United States

RECRUITING

Northwestern University CRS

Chicago, Illinois, 60611, United States

NOT YET RECRUITING

Massachusetts General Hospital CRS (MGH CRS)

Boston, Massachusetts, 02114, United States

RECRUITING

Washington University Therapeutics (WT) CRS

St Louis, Missouri, 63110-1010, United States

RECRUITING

New Jersey Medical School Clinical Research Center CRS (Site ID 31786)

Newark, New Jersey, 07103, United States

RECRUITING

Weill Cornell Chelsea CRS

New York, New York, 10010, United States

NOT YET RECRUITING

Columbia Physicians & Surgeons (P&S) CRS

New York, New York, 10032, United States

NOT YET RECRUITING

Weill Cornell Uptown CRS

New York, New York, 10065, United States

NOT YET RECRUITING

University of Rochester Adult HIV Therapeutic Strategies Network CRS

Rochester, New York, 14642, United States

NOT YET RECRUITING

Chapel Hill CRS

Chapel Hill, North Carolina, 27599-7215, United States

RECRUITING

Greensboro CRS

Greensboro, North Carolina, 27401-1020, United States

RECRUITING

Cincinnati CRS

Cincinnati, Ohio, 45267-0405, United States

RECRUITING

Case CRS

Cleveland, Ohio, 44106, United States

NOT YET RECRUITING

Ohio State University CRS

Columbus, Ohio, 43210, United States

RECRUITING

Penn Therapeutics CRS

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

University of Pittsburgh CRS

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

Vanderbilt Therapeutics (VT) CRS

Nashville, Tennessee, 37204, United States

NOT YET RECRUITING

Houston Advancing Research Team CRS

Houston, Texas, 77030, United States

NOT YET RECRUITING

Gaborone CRS

Gaborone, Botswana

NOT YET RECRUITING

Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS

Rio de Janeiro, 21040-900, Brazil

NOT YET RECRUITING

Byramjee Jeejeebhoy Medical College (BJMC) CRS

Pune, Maharashtra, 411001, India

NOT YET RECRUITING

Moi University Clinical Research Center (MUCRC) CRS

Eldoret, Rift Valley, 30100, Kenya

NOT YET RECRUITING

Kenya Medical Research Institute/Walter Reed Project Clinical Research Center (KEMRI/WRP) CRS

Kericho, Rift Valley, 20200, Kenya

NOT YET RECRUITING

Blantyre CRS

Blantyre, 265, Malawi

NOT YET RECRUITING

Nutrición-Mexico CRS

Mexico City, Tlalpan, 14080, Mexico

NOT YET RECRUITING

Barranco CRS

Lima, 15063, Peru

NOT YET RECRUITING

De La Salle Medical and Health Sciences Institute - Angelo King Medical Research Center (DLSMHSI-AKMRC)

Dasmariñas, Cavite, 4114, Philippines

NOT YET RECRUITING

Durban International CRS

Mount Edgecombe, 4302, South Africa

NOT YET RECRUITING

Thai Red Cross AIDS Research Centre (TRC-ARC) CRS

Pathum Wan, Bangkok, 10330, Thailand

NOT YET RECRUITING

Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS

Chiang Mai, 50200, Thailand

NOT YET RECRUITING

Joint Clinical Research Centre (JCRC)/Kampala CRS

Kampala, Uganda

NOT YET RECRUITING

Hanoi Medical University (HMU)

Hanoi, 10000, Vietnam

NOT YET RECRUITING

Milton Park CRS

Milton Park, Harare, Zimbabwe

NOT YET RECRUITING

Related Publications (3)

• Goodkin K, Evering TH, Anderson AM, Ragin A, Monaco CL, Gavegnano C, Avery RJ, Rourke SB, Cysique LA, Brew BJ. The comorbidity of depression and neurocognitive disorder in persons with HIV infection: call for investigation and treatment. Front Cell Neurosci. 2023 Apr 28;17:1130938. doi: 10.3389/fncel.2023.1130938. eCollection 2023.

  PMID: 37206666 BACKGROUND

• Cysique LA, Brew BJ, Bruning J, Byrd D, Costello J, Daken K, Ellis RJ, Fazeli PL, Goodkin K, Gouse H, Heaton RK, Letendre S, Levin J, Aung HL, Mindt MR, Moore D, Mullens AB, de Almeida SM, Munoz-Moreno JA, Power C, Robbins RN, Rule J, Rajasuriar R, Savin MJ, Taylor J, Trunfio M, Vance DE, Wong PL, Woods SP, Wright EJ, Rourke SB. Cognitive criteria in HIV: greater consensus is needed. Nat Rev Neurol. 2024 Feb;20(2):127-128. doi: 10.1038/s41582-024-00927-1. No abstract available.

  PMID: 38228906 BACKGROUND

• Goodkin K, Patten SB. Depressive Symptomatology, Syndromal Depression, and HIV-Associated Neurocognitive Disorder (HAND). Can J Psychiatry. 2018 May;63(5):284-286. doi: 10.1177/0706743718754537. No abstract available.

  PMID: 29668329 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Major; Neurocognitive Disorders

Interventions

Escitalopram

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• William R Short, MD

  University of Pennsylvania

  STUDY CHAIR

• Scott Letendre, MD

  University of California, San Diego

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2024
• First Posted: November 26, 2024
• Study Start: April 30, 2026
• Primary Completion (Estimated): December 2, 2026
• Study Completion (Estimated): December 2, 2026
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH.
• 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.

Locations

BR (1); IN (1); UG (1); US (25); KE (2); TH (2); PE (1); ME (1); VN (1); ZI (1); ZA (1); PH (1); BO (1); MA (1)