Clinical trial NCT00352885: Effectiveness of Escitalopram in Preventing or Reducing Depressive Symptoms in People Receiving Interleukin-2 Treatment
Official title: IL-2 Neuropsychiatric Symptoms: Mechanism and Prevention
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Depression
Keywords: Cancer
IL-2 therapy
Antidepressant
Immune system
Neuroendocrine response
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2006-07-17
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of IL-2 Treatments Tolerated
timeFrame: Cycle 4 (up to 12 weeks of IL-2 treatment)
Secondary outcomes:
measure: Plasma Concentrations of Adrenocorticotropic Hormone (ACTH)
timeFrame: Screening and Cycles 1 - 4 (up to 14 weeks)
measure: Plasma Concentrations of Interleukin 6 (IL-6)
timeFrame: Screening and Cycles 1 - 4 (up to 14 weeks)
measure: Plasma Concentrations of Cortisol
timeFrame: Screening and Cycles 1 - 4 (up to 14 weeks)
measure: Hamilton Depression Rating Scale (HAM-D) Score
timeFrame: Screening and Cycles 1 - 4 (up to 14 weeks)
measure: Genetic Polymorphisms
timeFrame: Screening and After Cycle 4 (up to 14 weeks)
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Winship Cancer Institute
state: Georgia
Study officials:
affiliation: Emory University
name: Dominique L. Musselman, MD,MS
role: PRINCIPAL_INVESTIGATOR
affiliation: Emory University
name: David Lawson, MD
role: STUDY_CHAIR
affiliation: Emory University
name: Andrew Miller, MD
role: STUDY_CHAIR
References:
citation: Musselman D, Royster EB, Wang M, Long Q, Trimble LM, Mann TK, Graciaa DS, McNutt MD, Auyeung NS, Oliver L, Lawson DH, Miller AH. The impact of escitalopram on IL-2-induced neuroendocrine, immune, and behavioral changes in patients with malignant melanoma: preliminary findings. Neuropsychopharmacology. 2013 Sep;38(10):1921-8. doi: 10.1038/npp.2013.85. Epub 2013 Apr 10.
citation: McNutt MD, Liu S, Manatunga A, Royster EB, Raison CL, Woolwine BJ, Demetrashvili MF, Miller AH, Musselman DL. Neurobehavioral effects of interferon-alpha 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.