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Pramipexole versus escitalopram for depression and mild cognitive problems in people living with HIV

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

Phase 2 Interventional National Institute of Allergy and Infectious Diseases (NIAID) · NCT06705478

This Phase II trial tests whether pramipexole extended-release works better than escitalopram for treating major depression, including when mild cognitive problems are present, in people living with HIV.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment186 (estimated)
Ages18 Years to 70 Years
SexAll
SponsorNational Institute of Allergy and Infectious Diseases (NIAID) NIH
Locations40 sites (Birmingham, Alabama and 39 other locations)
Trial IDNCT06705478 on ClinicalTrials.gov

What this trial studies

This is a randomized, open-label, two-arm Phase II trial comparing pramipexole ER to escitalopram in adults with HIV who have major depressive disorder, with or without comorbid mild neurocognitive disorder. Participants will be randomized to one of the two medications and seen regularly for safety monitoring, symptom response, and dose adjustments. Eligible participants must have documented HIV-1 infection, be on a stable ART regimen for at least 90 days with plasma HIV-1 RNA <200 copies/mL, and meet antidepressant washout requirements where applicable. An optional sub-study will enroll up to 36 participants to examine treatment effects on cerebrospinal fluid markers.

Who should consider this trial

Good fit: Ideal candidates are adults living with HIV who have major depressive disorder (with or without mild neurocognitive disorder), are on stable ART with viral suppression, and can comply with antidepressant washout and study visits.

Not a fit: People with uncontrolled HIV, those unable to stop current antidepressants per the protocol, those with more than mild cognitive impairment, pregnant individuals, or those unwilling to attend study visits or procedures may not benefit from participation.

Why it matters

Potential benefit: If successful, this comparison could offer an alternative antidepressant that improves mood and possibly cognitive symptoms for people living with HIV.

How similar studies have performed: Small trials and case reports have suggested pramipexole can relieve depressive symptoms, but its use specifically in people with HIV and comorbid mild neurocognitive disorder remains limited and not well established.

Eligibility criteria

Show full inclusion / exclusion criteria 
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.

Where this trial is running

Birmingham, Alabama and 39 other locations

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Major Depressive DisorderMild Neurocognitive DisorderHIVComorbid MND
Last reviewed 2026-06-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.