DepressionPhase 4NCT02620150
SSRI Effects on Depression and Immunity in HIV/AIDS
A Phase 4 study testing Escitalopram in people with Depression and HIV, run by University of Pennsylvania at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Depression, HIV, AIDS
- What is being tested?
- Escitalopram
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 108 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Feb 2017to 31 Mar 2022
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women aged 18-70 years, of any race and ethnicity,
- HIV-seropositive by ELISA and Western Blot assays, infected by behavioral transmission (perinatal HIV excluded),
- Willing and able to comply with antidepressant medication regimen and scheduled follow-up visits,
- Currently on a documented regimen of cART for at least 3 months and Viral load less than 200 copies/ml,
- 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)
- Able to understand and provide informed consent.
Who cannot join
- 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),
- Significant cognitive impairment or dementia including HIV Associated Dementia (HAD),
- 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,),
- Immunization with HIV vaccine,
- Presence of psychotic symptoms or known diagnosis of a primary psychotic disorder,
- Currently taking an anti-psychotic medication,
Show all 20Show fewer
- Pregnant or within nine months post-delivery, lactation,
- Current or chronic medical condition that would likely preclude adherence to protocol or completion of the trial (per investigator judgment),
- Bipolar disorder (I or II) or schizophrenia,
- Current pharmacotherapy for treatment of depression,
- A history of intolerance or nonresponse to an adequate trial of escitalopram (or other SSRIs),
- Renal failure, including those who require dialysis,
- History of epilepsy or seizure disorder,
- Taken MAOIs within 14 days,
- On the antibiotic Linezolid and taking IV methylene blue,
- On a regular regime of medication known to have anticoagulant properties such as NSAID, aspirin or warfarin,
- A history of acute narrow/closed angle glaucoma,
- Currently taking CNS drugs (the following are not excluded: gabapentin, pregabalin, varenicline, antihistamines, and hypnotics (e.g. zolpidem, zaleplon, eszopiclone),
- On any triptan medications,
- Undergoing ECT.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania Perelman School of Medicine
Philadelphia, Pennsylvania, 19104
About this study
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.
Read the 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.
- Conditions
- Depression, HIV, AIDS
- Being tested
- Escitalopram, Placebo
- Keywords
- HIV, AIDS, Depression, SSRI, Escitalopram, Immunity
- Medical subject headings
- Depression, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EscitalopramDrug
10 week trial
PlaceboOther
10 week trial
| Study group | Role | What they receive |
|---|---|---|
| Experimental | 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. Receives: Drug: Escitalopram |
| Placebo | Placebo comparator | 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. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Post randomization to 10 weeks
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.
Measured: Post randomization to 10 weeks
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.
Measured: Post randomization to 10 weeks
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.
Measured: Post randomization to 10 weeks
Secondary outcomes (4)
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.
Measured: 10 weeks
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)
Measured: 10 weeks
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)
Measured: 10 weeks
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)
Measured: 10 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2015 (estimated)
- Study start16 Feb 2017
- Primary completion31 Mar 2022
- Study completion31 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 108 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dwight L Evans, MD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02620150
- Sponsor's protocol ID
- 823405
- Status last verified
- Apr 2024
- First submitted
- 20 Nov 2015
- Last updated
- 7 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SSRI Effects on Depression and Immunity in HIV/AIDS
- ClinicalTrials.gov ID
- NCT02620150
- Acronym / sponsor ID
- 823405
- Conditions
- Depression, HIV, AIDS
- Keywords
- HIV, AIDS, Depression, SSRI, Escitalopram, Immunity
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 108 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 16 Feb 2017 (actual)
- Primary completion
- 31 Mar 2022 (actual)
- Study completion
- 31 Mar 2022 (actual)
- First posted
- 2 Dec 2015 (estimated)
- Results
- Posted 7 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Drug: EscitalopramCCBT 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. |
| Placebo | Placebo comparator | Other: PlaceboCCBT 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Men and women aged 18-70 years, of any race and ethnicity,
- HIV-seropositive by ELISA and Western Blot assays, infected by behavioral transmission (perinatal HIV excluded),
- Willing and able to comply with antidepressant medication regimen and scheduled follow-up visits,
- Currently on a documented regimen of cART for at least 3 months and Viral load less than 200 copies/ml,
- 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)
Key exclusion criteria (20 listed)
- 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),
- Significant cognitive impairment or dementia including HIV Associated Dementia (HAD),
- 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,),
- Immunization with HIV vaccine,
- Presence of psychotic symptoms or known diagnosis of a primary psychotic disorder,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Escitalopram10 week trial | Drug | Experimental |
| Placebo10 week trial | Other | Placebo |
Primary outcome
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.]
Time frame: 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)
Time frame: 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
Time frame: 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.
Units of Concentration of Plasma C-Reactive Protein (CRP), Expressed as Milligrams Per Liter
Time frame: 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.
4 secondary outcomes
Correlation Between Change in Overall Score on the Hamilton Depression Rating Scale, and Change in Natural Killer Cell Activity
Time frame: 10 weeks
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)
Time frame: 10 weeks
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
Time frame: 10 weeks
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
Time frame: 10 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dwight L Evans, MD principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Escitalopram in people with Depression and HIV, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.] (time frame: Post randomization to 10 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2024.