HIV, Major Depressive Disorder, Mild Neurocognitive Disorder
Conditions
Keywords
Comorbid MND
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.
Interventions
DRUGPramipexole ER
Tablets self-administered orally
DRUGEscitalopram
Tablets self-administered orally
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Cipla Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 | — |
| Change in the MOS-HIV cognitive functioning subscale score defined by the MOS-HIV Users Manual | Baseline, 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 | — |
| Occurrence of 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 | — |
Countries
Botswana, Brazil, India, Kenya, Malawi, Mexico, Peru, Philippines, South Africa, Thailand, Uganda, United States, Vietnam, Zimbabwe
Contacts
STUDY_CHAIRWilliam R Short, MD
University of Pennsylvania
STUDY_CHAIRScott Letendre, MD
University of California, San Diego
Outcome results
None listed