Evaluating the Effectiveness of Escitalopram in Preventing or Reducing Depressive Symptoms in People Receiving Interleukin-2 Treatment

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00352885
Recruitment Status : Completed
First Posted : July 17, 2006
Results First Posted : June 27, 2014
Last Update Posted : October 9, 2014
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Andrew H Miller, Emory University

July 13, 2006
July 17, 2006
March 8, 2014
June 27, 2014
October 9, 2014
January 2006
May 2010   (Final data collection date for primary outcome measure)
Number of IL-2 Treatments Tolerated [ Time Frame: Measured over 5 months of treatment ]
  • Define the mechanisms by which IV IL-2 administration contributes to CNS dysfunction, including activation of pathways related to:
  • the immune system by measuring the cytokines IL-1, IL-4, IL-6, IL-10, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha and relevant cytokine signaling pathways.
  • the neuroendocrine system by measuring ACTH, cortisol, and glucocorticoid sensitivity in response to dexamethasone
  • serotonin metabolism as measured by circulating concentrations of the serotonin (5HT) precursor, L-tryptophan (TRP,
  • cognitive function by computerized neuropsychological testing,
  • genetic polymorphisms relevant to the above mentioned biomarkers .
Complete list of historical versions of study NCT00352885 on Archive Site
  • Neuroendocrine System Functioning and Stress Hormone Levels [ Time Frame: Measured over 5 months of IL-2 treatment ]
  • Immune System Functioning [ Time Frame: Measured over 5 months of IL-2 treatment ]
  • Serotonin Metabolism [ Time Frame: Measured over 5 months of IL-2 treatment ]
  • Cognitive Functioning, as Assessed by Computerized Neuropsychological Testing [ Time Frame: Measured on Day 2 of each IL-2 cycle ]
  • Genetic Polymorphisms [ Time Frame: Measured before and after IL-2 treatment ]
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Evaluating the Effectiveness of Escitalopram in Preventing or Reducing Depressive Symptoms in People Receiving Interleukin-2 Treatment
IL-2 Neuropsychiatric Symptoms: Mechanism and Prevention
This study will determine the effectiveness of an antidepressant in preventing or reducing depressive symptoms in people with melanoma who are receiving Interleukin-2 (IL-2) treatment.

Melanoma is the most serious type of skin cancer, affecting nearly 54,000 people in the United States each year. Melanomas often develop in pre-existing moles or as new moles on the body. If left untreated, the cancerous cells can spread throughout the body. Fortunately, melanoma can be cured if a person is diagnosed and treated early. Typical treatments include surgery, amputation, chemotherapy, and immunotherapy. Interleukin-2 (IL-2) treatment, a type of immunotherapy, uses the body's immune system to slow or stop the spread of cancer cells to other parts of the body. However, IL-2 treatment is typically associated with severe side effects, including depression, fatigue, and difficulty thinking. This study will evaluate whether escitalopram, an antidepressant, can help improve treatment-related depressive symptoms, reduce stress hormone levels, and increase the number of treatment cycles among people with metastatic melanoma who are receiving IL-2 treatment.

Participation in this double-blind study will last up to 18 weeks and will include 5 to 14 study visits. Participants will complete four 1-week cycles of IL-2 treatment over a 12-week period. Two weeks prior to starting IL-2 treatment, participants will undergo a psychiatric interview; a computerized thinking test; questionnaires; and blood, urine, and saliva collection. Participants will also be randomly assigned to start receiving either escitalopram or placebo for the entire duration of the study. The dosage of escitalopram or placebo will vary depending on the symptom severity of each participant. Immediately prior to IL-2 treatment, participants will undergo preliminary IL-2 procedures, which will include a medical history review, physical exam, and blood collection. These same procedures will occur every day that the participant is in the hospital for IL-2 treatment. Participants will stay in the hospital when receiving all four IL-2 treatment cycles. During these hospital stays, participants will complete repeat questionnaires and computerized tasks. Blood collection will occur at selected times as well. A follow-up visit will occur 4 weeks after the final treatment dose of IL-2.

Phase 4
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
  • Drug: Escitalopram
    Participants will begin medication approximately 2 weeks before their first scheduled IL-2 treatment. The dosage for the first week will be 10 mg per day. If 10 mg is well tolerated by the participant, the dosage will be increased to 20 mg per day. The dosage for the remainder of the study will be 20 mg per day.
    Other Name: Lexapro
  • Drug: Placebo
    Participants will begin the placebo approximately 2 weeks before their first scheduled IL-2 treatment. The dosage for the first week will be 1 pill per day, if 1 pill is well tolerated by the participant the dosage will be increased to 2 pills per day. Two pills per day will be the dosage for the reminder of the study.
    Other Name: Sugar pill
  • Drug: IL-2
    IL-2 is a 12-week treatment regimen with intravenous (IV) IL-2. There will be one cycle every 3 weeks for a total of four cycles. One cycle is 720,000 units/kg every 8 hours for 5 days.
  • Experimental: A
    Participants will receive escitalopram and IL-2 treatment
    • Drug: Escitalopram
    • Drug: IL-2
  • Placebo Comparator: B
    Participants will receive placebo and IL-2 treatment
    • Drug: Placebo
    • Drug: IL-2
McNutt MD, Liu S, Manatunga A, Royster EB, Raison CL, Woolwine BJ, Demetrashvili MF, Miller AH, Musselman DL. Neurobehavioral effects of interferon-α in patients with hepatitis-C: symptom dimensions and responsiveness to paroxetine. Neuropsychopharmacology. 2012 May;37(6):1444-54. doi: 10.1038/npp.2011.330. Epub 2012 Feb 22.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
May 2010
May 2010   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Diagnosed with cancer and beginning Interleukin (IL)-2 treatment
  • Willing to use an effective form of birth control throughout the study if sexually active

Exclusion Criteria:

  • Diagnosed with major depression or experiencing significant depressive symptoms or a Hamilton Rating Scale-Depression score of 18 or higher
  • Brain metastases, history of a brain injury, or seizure disorders
  • Meets Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria for substance abuse or dependence within 3 months of study entry
  • Suicidal, psychotic, or received psychiatric hospitalization within 12 months of study entry
  • Past or current history of schizophrenia or bipolar disorder
  • Pregnant or planning on becoming pregnant within 1 to 2 years
  • Evidence of untreated or poorly controlled infectious, hormone, heart, blood, kidney, liver, or neurological disease
  • Use of antidepressants, glucocorticoids, guanethidine, centrally acting alpha-antagonists, beta-blockers, or anticonvulsants
  • Clinically significant eye abnormalities
  • A score lower than 28 on the Mini Mental Status Exam (MMSE)
  • Prior history of severe adverse events associated with escitalopram or other selective serotonin reuptake inhibitor (SSRI) antidepressants
  • Diagnosed with type 1 or type 2 diabetes
  • Any condition that might make the participant unsuitable for enrollment or that could interfere with study participation
Sexes Eligible for Study: All
18 Years to 75 Years   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
United States
R01MH071580 ( U.S. NIH Grant/Contract )
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Andrew H Miller, Emory University
Emory University
National Institute of Mental Health (NIMH)
Principal Investigator: Dominique L. Musselman, MD,MS Emory University
Study Chair: David Lawson, MD Emory University
Study Chair: Andrew Miller, MD Emory University
Emory University
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP