SSRI Effects on Depression and Immunity in HIV/AIDS

NCT02620150 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: 823405
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

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.

Conditions

Depression; HIV; AIDS

Keywords

HIV; AIDS; Depression; SSRI; Escitalopram; Immunity

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  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.

  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

  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)

  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

  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

  10 weeks

Study Arms (2)

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.

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.

Other: Placebo

Interventions

Escitalopram DRUG

10 week trial

Experimental

Placebo OTHER

10 week trial

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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,
• 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,

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

University of Pennsylvania Perelman School of Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Depression; Acquired Immunodeficiency Syndrome

Interventions

Escitalopram

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Chelsea Voytek
• Organization: University of Pennsylvania

chelseav@pennmedicine.upenn.edu

215-746-3711

Study Officials

• Dwight L Evans, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2015
• First Posted: December 2, 2015
• Study Start: February 16, 2017
• Primary Completion: March 31, 2022
• Study Completion: March 31, 2022
• Last Updated: May 7, 2024
• Results First Posted: May 7, 2024

Record last verified: 2024-04

Locations

US (1)