Clinical trial NCT06705478: Pramipexole Versus Escitalopram to Treat Major Depressive Disorder (MDD) and Comorbid MDD With Mild Neurocognitive Disorder (MND) in Persons With HIV
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Major Depressive Disorder
Mild Neurocognitive Disorder
HIV
Keywords: Comorbid MND
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Cipla Ltd.
First posted: 2024-11-26
Enrollment: 186
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Change in Beck Depression Inventory-II (BDI-II/BDI-2) total score defined as the sum of all symptom scores
timeFrame: Baseline, Week 24
measure: Occurrence of Grade ≥3 Adverse Events (AEs) or Grade ≥2 neuropsychiatric AEs related to study treatment
timeFrame: From study treatment administration through Week 24
measure: Occurrence of Grade ≥2 neuropsychiatric AEs related to study treatment
timeFrame: From study treatment administration through Week 24
Secondary outcomes:
measure: 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
timeFrame: Baseline, Week 24
measure: Complete remission of the major depressive episode defined as a score of 0 on all of the 9 symptoms
timeFrame: Baseline, Week 24
measure: Change in neuropsychological (NP) z-score as assessed through 4 composite domain scores
timeFrame: Baseline, Week 24
measure: Change in the medical outcomes study (MOS)-HIV mental health functioning summary score defined by the MOS-HIV Users Manual
timeFrame: Baseline, Week 24
measure: Change in the MOS-HIV cognitive functioning subscale score defined by the MOS-HIV Users Manual
timeFrame: Baseline, Week 24
measure: Occurrence of Grade ≥3 AEs or Grade ≥2 neuropsychiatric AEs (regardless of judged relationship to study treatment)
timeFrame: From study treatment administration through Week 24
measure: Occurrence of Grade ≥2 neuropsychiatric AEs (regardless of judged relationship to study treatment)
timeFrame: From study treatment administration through Week 24
measure: Number of participants with plasma HIV-1 RNA less than 50 copies/mL
timeFrame: Week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama CRS
state: Alabama
city: Los Angeles
country: United States
facility: University of California, Los Angeles CARE Center CRS
state: California
city: San Diego
country: United States
facility: UCSD Antiviral Research Center CRS
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco HIV/AIDS CRS
state: California
city: Torrance
country: United States
facility: Harbor University of California, Los Angeles Center CRS
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital CRS
state: Colorado
city: Washington
country: United States
facility: Whitman-Walker Institute, Inc. CRS
state: District of Columbia
city: Atlanta
country: United States
facility: The Ponce de Leon Center CRS
state: Georgia
city: Chicago
country: United States
facility: Northwestern University CRS
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital CRS (MGH CRS)
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University Therapeutics (WT) CRS
state: Missouri
city: New York
country: United States
facility: Weill Cornell Chelsea CRS
state: New York
city: New York
country: United States
facility: Columbia Physicians & Surgeons (P&S) CRS
state: New York
city: New York
country: United States
facility: Weill Cornell Uptown CRS
state: New York
city: Rochester
country: United States
facility: University of Rochester Adult HIV Therapeutic Strategies Network CRS
state: New York
city: Chapel Hill
country: United States
facility: Chapel Hill CRS
state: North Carolina
city: Greensboro
country: United States
facility: Greensboro CRS
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati CRS
state: Ohio
city: Cleveland
country: United States
facility: Case CRS
state: Ohio
city: Columbus
country: United States
facility: Ohio State University CRS
state: Ohio
city: Philadelphia
country: United States
facility: Penn Therapeutics CRS
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh CRS
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Therapeutics (VT) CRS
state: Tennessee
city: Houston
country: United States
facility: Houston Advancing Research Team CRS
state: Texas
city: Gaborone
country: Botswana
facility: Gaborone CRS
city: Rio De Janeiro
country: Brazil
facility: Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS
city: Pune
country: India
facility: Byramjee Jeejeebhoy Medical College (BJMC) CRS
state: Maharashtra
city: Eldoret
country: Kenya
facility: Moi University Clinical Research Center (MUCRC) CRS
state: Rift Valley
city: Kericho
country: Kenya
facility: Kenya Medical Research Institute/Walter Reed Project Clinical Research Center (KEMRI/WRP) CRS
state: Rift Valley
city: Blantyre
country: Malawi
facility: Blantyre CRS
city: Mexico City
country: Mexico
facility: Nutrición-Mexico CRS
state: Tlalpan
city: Lima
country: Peru
facility: Barranco CRS
city: Dasmariñas
country: Philippines
facility: De La Salle Medical and Health Sciences Institute - Angelo King Medical Research Center (DLSMHSI-AKMRC)
state: Cavite
city: Mount Edgecombe
country: South Africa
facility: Durban International CRS
city: Pathum Wan
country: Thailand
facility: Thai Red Cross AIDS Research Centre (TRC-ARC) CRS
state: Bangkok
city: Chiang Mai
country: Thailand
facility: Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS
city: Kampala
country: Uganda
facility: Joint Clinical Research Centre (JCRC)/Kampala CRS
city: Hanoi
country: Vietnam
facility: Hanoi Medical University (HMU)
city: Milton Park
country: Zimbabwe
facility: Milton Park CRS
state: Harare
Study officials:
affiliation: Neuropsychiatrist Consultant
name: Karl Goodkin, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.