AIDS, Depression, HIV
Conditions
Keywords
HIV, AIDS, Depression, SSRI, Escitalopram, Immunity
Brief summary
This is a 10 week, double-blind, placebo controlled trial to evaluate SSRI (Selective Serotonin Reuptake Inhibitor) effects for treatment of depression in HIV/AIDS with a focus on innate immunity and inflammation. Depressed population is HIV + on cART (Combination Antiretroviral Therapy), not currently on pharmacotherapy for depression. Subjects will complete computerized cognitive behavior therapy, CCBT for their depression. Blood samples collected for virologic, neuroendocrine, and immunologic evaluation. Our overarching hypothesis is that SSRI treatment of depression and improvement of depressive symptoms leads to increased innate immunity and decreased inflammation, resulting in better control of HIV disease and decreased morbidity.
Detailed description
To pursue our long-term objective of successfully treating co-morbid mental and medical disorders in HIV/AIDS, this study aims to determine whether: 1) SSRI treatment significantly increases innate immunity and decreases chronic inflammation and immune activation, and 2) changes in depressive symptoms correlate with changes in immunity in HIV/AIDS. HIV-seropositive, depressed subjects will be randomized to 10 weeks of double blind therapy with either escitalopram or placebo. All participants will concurrently begin CCBT (Computerized Cognitive Behavioral Therapy) using the program Good Days Ahead. Subject visits will occur weekly for the first 6 weeks and then at weeks 8 and 10. The treating clinician will assess side effects, review symptomatic progress, and adjust the study medication as clinically appropriate. An independent clinical evaluator will assess patients at baseline, and weeks 1-6, 8 and 10. Blood samples collected at baseline and weeks 2, 4, and 10 will be used to assay markers of innate immune suppression (lytic units of NK cells, LUNK, and intracellular IFN gamma in NK cells) and markers of inflammation (IL-6 and C-Reactive Protein). At the end of the 10-week treatment phase, all participants will be referred for appropriate clinical treatment of their depression.
Interventions
DRUGEscitalopram
10 week trial
OTHERPlacebo
10 week trial
Sponsors
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Men and women aged 18-70 years, of any race and ethnicity, 2. HIV-seropositive by ELISA and Western Blot assays, infected by behavioral transmission (perinatal HIV excluded), 3. Willing and able to comply with antidepressant medication regimen and scheduled follow-up visits, 4. Currently on a documented regimen of cART for at least 3 months and Viral load less than 200 copies/ml, 5. Current depressive symptoms (HAM-D-17 score ≥ 13 and a SCID diagnosis of either Major Depressive Disorder, Persistent Depressive Disorder (Dysthymia), Unspecified Depressive Disorder, or Other Specified Depressive Disorder) 6. Able to understand and provide informed consent.
Exclusion criteria
1. Acute suicidal ideation, gestures, or attempts (e.g., HAM-D suicide item score of 3 Ideas or gestures of suicide or 4 Attempts at suicide at intake or HAM-D suicide item score of 4 Attempts at suicide during study), 2. Significant cognitive impairment or dementia including HIV Associated Dementia (HAD), 3. Use of a medication known to alter immune function within 4 weeks prior to randomization (the following are not excluded: a. acyclovir and related antiviral medications, b. topical corticosteroids, c. corticosteroid nasal sprays or inhalers, d) statin medications,), 4. Immunization with HIV vaccine, 5. Presence of psychotic symptoms or known diagnosis of a primary psychotic disorder, 6. Currently taking an anti-psychotic medication, 7. Pregnant or within nine months post-delivery, lactation, 8. Current or chronic medical condition that would likely preclude adherence to protocol or completion of the trial (per investigator judgment), 9. Bipolar disorder (I or II) or schizophrenia, 10. Current pharmacotherapy for treatment of depression, 11. A history of intolerance or nonresponse to an adequate trial of escitalopram (or other SSRIs), 12. Renal failure, including those who require dialysis, 13. History of epilepsy or seizure disorder, 14. Taken MAOIs within 14 days, 15. On the antibiotic Linezolid and taking IV methylene blue, 16. On a regular regime of medication known to have anticoagulant properties such as NSAID, aspirin or warfarin, 17. A history of acute narrow/closed angle glaucoma, 18. Currently taking CNS drugs (the following are not excluded: gabapentin, pregabalin, varenicline, antihistamines, and hypnotics (e.g. zolpidem, zaleplon, eszopiclone), 19. On any triptan medications, 20. Undergoing ECT.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Units of Concentration of Plasma C-Reactive Protein (CRP), Expressed as Milligrams Per Liter | Post randomization to 10 weeks | The outcome was determined by biological assays, which determined the concentration of CRP, expressed as mg/l. Higher concentrations indicate greater inflammation. In the present summaries, we calculated the within-participant median value of the outcome over their available data at weeks 2, 4 and 10, and obtained overall and within-group summaries for these within-participant distributions. |
| Natural Killer Cell Activity, Measured in Lytic Units [Bryant J, Day R, Whiteside TL, and Herbeman RB: Calculation of Lytic Units for the Expression of Cell-mediated Cytotoxicity. J Immunol Methods 1992;146:91-103.] | Post randomization to 10 weeks | The outcome was determined by biological assays. Natural killer cells (NK cells) are white blood cells, a type of lymphocytes, that destroy infected and cancer cells through antigen independent recognition. Higher numbers indicate higher levels of cytotoxicity, that is, stronger cellular response. In the present summaries, we calculated the within-participant median value of the outcome over their available data at weeks 2, 4 and 10, and obtained overall and within-group summaries for these within-participant distributions. |
| Percent of Natural Killer (NK) Cells Producing Intracellular Interferon Gamma (IFN-g) | Post randomization to 10 weeks | The outcome was determined by biological assays, which determined the number of NK cells, and the number of these cells that produced IFN-g, and combined these to calculate the outcome. Higher numbers are associated with stronger cellular response. In the present summaries, we calculated the within-participant median value of the outcome over their available data at weeks 2, 4 and 10, and obtained overall and within-group summaries for these within-participant distributions. |
| Units of Concentration of Plasma Interleukin 6 (IL-6), Expressed as Picograms Per Milliliter | Post randomization to 10 weeks | The outcome was determined by biological assays, which determined the concentration of IL-6, expressed as pg/ml. Higher concentrations indicate greater inflammation. In the present summaries, we calculated the within-participant median value of the outcome over their available data at weeks 2, 4 and 10, and obtained overall and within-group summaries for these within-participant distributions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation Between Change in Overall Score on the Hamilton Depression Rating Scale, and Change in Natural Killer Cell Activity | 10 weeks | The outcome was determined by calculating the Spearman correlation between decrease in overall score on the Hamilton Depression Rating Scale and decrease on Natural killer cell activity. |
| Correlation Between Change in Overall Score on the Hamilton Depression Rating Scale, and Change in Percent of Natural Killer (NK) Cells Producing Intracellular Interferon Gamma (IFN-g) | 10 weeks | The outcome was determined by calculating the Spearman correlation between decrease in overall score on the Hamilton Depression Rating Scale and decrease on the Percent of Natural Killer (NK) Cells Producing Intracellular Interferon Gamma (IFN-g) |
| Correlation Between Change in Overall Score on the Hamilton Depression Rating Scale, and Change in Units of Concentration of Plasma Interleukin 6 (IL-6), Expressed as Picograms Per Milliliter | 10 weeks | The outcome was determined by calculating the Spearman correlation between decrease in overall score on the Hamilton Depression Rating Scale and decrease on Units of Concentration of Plasma Interleukin 6 (IL-6) |
| Correlation Between Change in Overall Score on the Hamilton Depression Rating Scale, and Change in Units of Concentration of Plasma C-Reactive Protein (CRP), Expressed as Milligrams Per Liter | 10 weeks | The outcome was determined by calculating the Spearman correlation between decrease in overall score on the Hamilton Depression Rating Scale and decrease on Units of Concentration of Plasma C-Reactive Protein (CRP) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Experimental CCBT plus Escitalopram, oral, for 10 weeks, once daily, starting at 10mg/day. Tapered up or down, based on tolerability and clinical response, to 20mg/day max.
Escitalopram: 10 week trial | 55 |
| Placebo CCBT plus Placebo, oral, for 10 weeks, once daily, starting at 10mg/day. Tapered up or down, based on tolerability and clinical response, to 20mg/day max.
Placebo: 10 week trial | 53 |
| Total | 108 |
Baseline characteristics
| Characteristic | Placebo | Experimental | Total |
|---|---|---|---|
| Age, Continuous | 49.87 years STANDARD_DEVIATION 10.97 | 49.95 years STANDARD_DEVIATION 11.99 | 49.91 years STANDARD_DEVIATION 11.45 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 4 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 46 Participants | 50 Participants | 96 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Overall Score on the Hamilton Depression Rating Scale | 19.21 units on a scale STANDARD_DEVIATION 5.07 | 19.13 units on a scale STANDARD_DEVIATION 4.9 | 19.17 units on a scale STANDARD_DEVIATION 4.96 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 47 Participants | 49 Participants | 96 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 4 Participants | 5 Participants | 9 Participants |
| Sex/Gender, Customized Female | 20 Participants | 20 Participants | 40 Participants |
| Sex/Gender, Customized Male | 32 Participants | 34 Participants | 66 Participants |
| Sex/Gender, Customized Transgender Female | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 55 | 0 / 53 |
| other Total, other adverse events | 33 / 55 | 36 / 53 |
| serious Total, serious adverse events | 2 / 55 | 1 / 53 |
Outcome results
Primary
Natural Killer Cell Activity, Measured in Lytic Units [Bryant J, Day R, Whiteside TL, and Herbeman RB: Calculation of Lytic Units for the Expression of Cell-mediated Cytotoxicity. J Immunol Methods 1992;146:91-103.]
The outcome was determined by biological assays. Natural killer cells (NK cells) are white blood cells, a type of lymphocytes, that destroy infected and cancer cells through antigen independent recognition. Higher numbers indicate higher levels of cytotoxicity, that is, stronger cellular response. In the present summaries, we calculated the within-participant median value of the outcome over their available data at weeks 2, 4 and 10, and obtained overall and within-group summaries for these within-participant distributions.
Time frame: Post randomization to 10 weeks
Population: 96 participants who provided responses at any of weeks 2, 4, and 10
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Experimental | Natural Killer Cell Activity, Measured in Lytic Units [Bryant J, Day R, Whiteside TL, and Herbeman RB: Calculation of Lytic Units for the Expression of Cell-mediated Cytotoxicity. J Immunol Methods 1992;146:91-103.] | 224.06 Lytic Units |
| Placebo | Natural Killer Cell Activity, Measured in Lytic Units [Bryant J, Day R, Whiteside TL, and Herbeman RB: Calculation of Lytic Units for the Expression of Cell-mediated Cytotoxicity. J Immunol Methods 1992;146:91-103.] | 252.02 Lytic Units |
Primary
Percent of Natural Killer (NK) Cells Producing Intracellular Interferon Gamma (IFN-g)
The outcome was determined by biological assays, which determined the number of NK cells, and the number of these cells that produced IFN-g, and combined these to calculate the outcome. Higher numbers are associated with stronger cellular response. In the present summaries, we calculated the within-participant median value of the outcome over their available data at weeks 2, 4 and 10, and obtained overall and within-group summaries for these within-participant distributions.
Time frame: Post randomization to 10 weeks
Population: 96 participants who provided responses at any of weeks 2, 4, and 10
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Experimental | Percent of Natural Killer (NK) Cells Producing Intracellular Interferon Gamma (IFN-g) | 8.25 Percentage of NK cells producing IFN-g |
| Placebo | Percent of Natural Killer (NK) Cells Producing Intracellular Interferon Gamma (IFN-g) | 5.40 Percentage of NK cells producing IFN-g |
Primary
Units of Concentration of Plasma C-Reactive Protein (CRP), Expressed as Milligrams Per Liter
The outcome was determined by biological assays, which determined the concentration of CRP, expressed as mg/l. Higher concentrations indicate greater inflammation. In the present summaries, we calculated the within-participant median value of the outcome over their available data at weeks 2, 4 and 10, and obtained overall and within-group summaries for these within-participant distributions.
Time frame: Post randomization to 10 weeks
Population: 96 participants who provided responses at any of weeks 2, 4, and 10
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Experimental | Units of Concentration of Plasma C-Reactive Protein (CRP), Expressed as Milligrams Per Liter | 3.75 Concentration of CRP (mg / l) |
| Placebo | Units of Concentration of Plasma C-Reactive Protein (CRP), Expressed as Milligrams Per Liter | 3.17 Concentration of CRP (mg / l) |
Primary
Units of Concentration of Plasma Interleukin 6 (IL-6), Expressed as Picograms Per Milliliter
The outcome was determined by biological assays, which determined the concentration of IL-6, expressed as pg/ml. Higher concentrations indicate greater inflammation. In the present summaries, we calculated the within-participant median value of the outcome over their available data at weeks 2, 4 and 10, and obtained overall and within-group summaries for these within-participant distributions.
Time frame: Post randomization to 10 weeks
Population: 96 participants who provided responses at any of weeks 2, 4, and 10
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Experimental | Units of Concentration of Plasma Interleukin 6 (IL-6), Expressed as Picograms Per Milliliter | 2.52 Concentration of IL-6 (pcg/mL) |
| Placebo | Units of Concentration of Plasma Interleukin 6 (IL-6), Expressed as Picograms Per Milliliter | 3.17 Concentration of IL-6 (pcg/mL) |
Secondary
Correlation Between Change in Overall Score on the Hamilton Depression Rating Scale, and Change in Natural Killer Cell Activity
The outcome was determined by calculating the Spearman correlation between decrease in overall score on the Hamilton Depression Rating Scale and decrease on Natural killer cell activity.
Time frame: 10 weeks
Population: Participants who provided week 10 Hamilton Depression Rating Scale and Natural Killer cell activity data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental | Correlation Between Change in Overall Score on the Hamilton Depression Rating Scale, and Change in Natural Killer Cell Activity | 0.24 Correlation coefficient |
| Placebo | Correlation Between Change in Overall Score on the Hamilton Depression Rating Scale, and Change in Natural Killer Cell Activity | -0.28 Correlation coefficient |
Secondary
Correlation Between Change in Overall Score on the Hamilton Depression Rating Scale, and Change in Percent of Natural Killer (NK) Cells Producing Intracellular Interferon Gamma (IFN-g)
The outcome was determined by calculating the Spearman correlation between decrease in overall score on the Hamilton Depression Rating Scale and decrease on the Percent of Natural Killer (NK) Cells Producing Intracellular Interferon Gamma (IFN-g)
Time frame: 10 weeks
Population: Participants who provided week 10 Hamilton Depression Rating Scale and Intracellular Interferon Gamma (IFN-g) data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental | Correlation Between Change in Overall Score on the Hamilton Depression Rating Scale, and Change in Percent of Natural Killer (NK) Cells Producing Intracellular Interferon Gamma (IFN-g) | -0.01 Correlation coefficient |
| Placebo | Correlation Between Change in Overall Score on the Hamilton Depression Rating Scale, and Change in Percent of Natural Killer (NK) Cells Producing Intracellular Interferon Gamma (IFN-g) | 0.12 Correlation coefficient |
Secondary
Correlation Between Change in Overall Score on the Hamilton Depression Rating Scale, and Change in Units of Concentration of Plasma C-Reactive Protein (CRP), Expressed as Milligrams Per Liter
The outcome was determined by calculating the Spearman correlation between decrease in overall score on the Hamilton Depression Rating Scale and decrease on Units of Concentration of Plasma C-Reactive Protein (CRP)
Time frame: 10 weeks
Population: Participants who provided week 10 Hamilton Depression Rating Scale and Plasma C-Reactive Protein (CRP) data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental | Correlation Between Change in Overall Score on the Hamilton Depression Rating Scale, and Change in Units of Concentration of Plasma C-Reactive Protein (CRP), Expressed as Milligrams Per Liter | -0.33 Correlation coefficient |
| Placebo | Correlation Between Change in Overall Score on the Hamilton Depression Rating Scale, and Change in Units of Concentration of Plasma C-Reactive Protein (CRP), Expressed as Milligrams Per Liter | -0.04 Correlation coefficient |
Secondary
Correlation Between Change in Overall Score on the Hamilton Depression Rating Scale, and Change in Units of Concentration of Plasma Interleukin 6 (IL-6), Expressed as Picograms Per Milliliter
The outcome was determined by calculating the Spearman correlation between decrease in overall score on the Hamilton Depression Rating Scale and decrease on Units of Concentration of Plasma Interleukin 6 (IL-6)
Time frame: 10 weeks
Population: Participants who provided week 10 Hamilton Depression Rating Scale and Plasma Interleukin 6 (IL-6) data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental | Correlation Between Change in Overall Score on the Hamilton Depression Rating Scale, and Change in Units of Concentration of Plasma Interleukin 6 (IL-6), Expressed as Picograms Per Milliliter | -0.16 Correlation coefficient |
| Placebo | Correlation Between Change in Overall Score on the Hamilton Depression Rating Scale, and Change in Units of Concentration of Plasma Interleukin 6 (IL-6), Expressed as Picograms Per Milliliter | 0.16 Correlation coefficient |