Mental and Behavioural Disorders
Conditions
Interventions
Escitalopram
Pramipexole
Sponsors
National Institute of Allergy and Infectious Diseases
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria HIV-1, documented by: • Any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry AND • Confirmed by one of the following: o A second antibody test from different manufacturers or based on different principles and epitopes (combination antigen-antibody-based rapid tests may be used) o HIV-1 antigen o Plasma HIV-1 RNA viral load o A licensed Western blot NOTE: The term “licensed” refers to a US FDA-approved kit. WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot or an HIV-1 RNA viral load. Individuals age =18 to =70 years at randomization. Diagnosis of MDD (by DSM-5-TR criteria) [American Psychiatric Association 2022]. NOTE: MDD will be defined by the specific items from the BDI-II/BDI-2 that map to the DSM-5-TR diagnostic criteria for major depressive disorder as well as by significantly decreased functional status on the MOS-HIV mental health summary scale. See section 6.3 for details of the diagnosis of MDD as well as details of the diagnosis of MND. Though MND is not an entry criterion in this study, it is being investigated as a comorbidity with MDD. On current ART regimen for at least 90 days prior to study entry with no interruption in treatment (e.g., missed doses) >7 consecutive days. NOTE: A change of ART regimen to a regimen of greater convenience (e.g., lower pill burden) is allowed in the 90 days prior to study entry (assuming no interruption in treatment (e.g., missed doses) >7 consecutive days. No plans to change ART.
Exclusion criteria
Exclusion criteria: Active suicidality (as defined by presence of any level of suicidal ideation on item 9 of the BDI-II/BDI-2), and/or severe MDD (as defined by a BDI-II/BDI-2 score greater than 29), 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 as likely to affect study outcomes or to interfere with adherence to the study protocol. 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 (formerly denoted as “dependence”) by DSM-5-TR criteria in the 6 months prior to study entry. NOTE: Mild and moderate substance use disorder consistent with the former diagnosis of “abuse” will not be excluded. Active alcohol or substance use that, in the opinion of the site investigator, would interfere with study outcomes and/or adherence to the study protocol in persons without severe, active substance use disorder. 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 (as defined by the significant presence of at least one of the following: ascites encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, decompensated cirrhosis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 10.3Primary Outcome Measures 10.3.1Change in BDI-II/BDI-2 total score [Beck 1996] defined as the sum of all symptom scores from baseline to 24 weeks. The BDI-II/BDI-2 was revised with a major focus to include the nine symptoms of MDD published in the Diagnostic and Statistical Manual of Mental Disorders. Of note, it includes all of the symptoms measured by another commonly used measure of depressive symptoms, the PHQ-9-which was originally developed as a screening tool for MDD in primary care. Moreover, the BDI-II/BDI-2 includes a more comprehensive assessment of depressive symptoms in its total of 21 items than the PHQ-9. 10.3.2Occurrence of Grade =3 AEs or Grade =2 neuropsychiatric AEs (as well as specific analyses of sleep attacks, hallucinations, and impulsive behaviors known to be associated with pramipexole) related to study treatment (as judged by the site to be treatment-related) from study treatment administration through week 24. 10.3.3Occurrence of Grade =2 neuropsychiatric AEs related to study treatment (as judged by the site to be treatment-related) from study treatment administration through week 24. | — |
Secondary
| Measure | Time frame |
|---|---|
| 10.4 Secondary Outcome Measures 10.4.1 Change in MDD caseness, defined as the number of symptoms present from 0 to 9, of the symptoms of major depressive disorder from baseline to 24 weeks. The MDD caseness measure is based on the same nine MDD-defining symptoms included in the MDD diagnosis-while the BDI-II/BDI-2 measures these symptoms at an ordinal level, caseness will define them as present versus absent. The nine symptoms included are: depressed mood; loss of interest/pleasure; change in appetite; insomnia or hypersomnia; psychomotor agitation or retardation; fatigue; feeling worthless or excessive/inappropriate guilt; decreased concentration, and thoughts of death/suicide. 10.4.2 Complete remission of the major depressive episode. Complete remission is defined as a score of 0 on all of the 9 symptoms defined above. 10.4.3 Change in NP z-score from baseline to 24 weeks as assessed through 4 composite domain scores. 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]) 10.4.4 Change in the MOS-HIV mental health summary functioning scale score [Wojna 2018; Wu 1991] from baseline to week 24, defined by the MOS-HIV Users Manual. 10.4.5 Change in the MOS cognitive functioning subscale score from baseline to week 24, defined by the MOS-HIV Users Manual. NOTE: All primary and secondary outcomes above will be evaluated in the subsets of participants with MDD alone and participants with comorbid MDD and MND, change from baseline to 24 weeks. NOTE: All primary and secondary outcomes above will be evaluated by female versus male sex (assigned at birth). 10.4.6 Occurrence of Grade =3 AEs or Grade =2 neuropsychi | — |
Countries
Kenya
Contacts
Public ContactViola Kirui
Moi University
Outcome results
None listed