DepressionPhase 4NCT00352885
Effectiveness of Escitalopram in Preventing or Reducing Depressive Symptoms in People Receiving Interleukin-2 Treatment
A Phase 4 study testing Escitalopram and IL-2 in people with Depression, run by Emory University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Depression
- What is being tested?
- Escitalopram and IL-2
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Oct 2006to 17 May 2010
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosed with cancer and beginning Interleukin (IL)-2 treatment
- Willing to use an effective form of birth control throughout the study if sexually active
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Depression
- Being tested
- Escitalopram, Placebo, IL-2
- Keywords
- Cancer, IL-2 therapy, Antidepressant, Immune system, Neuroendocrine response
- Medical subject headings
- Depression, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EscitalopramDrug
Also called Lexapro
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.
PlaceboDrug
Also called Sugar pill
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.
IL-2Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Escitalopram | Experimental | Participants will receive escitalopram and IL-2 treatment Receives: Drug: Escitalopram; Drug: IL-2 |
| Placebo | Placebo comparator | Participants will receive placebo and IL-2 treatment Receives: Drug: Placebo; Drug: IL-2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of IL-2 Treatments Tolerated
The mean number of IL-2 doses tolerated (out of the possible 60 total doses) are presented for each study arm. The standard high dose regimen of IL-2 includes 15 doses per cycle. The dose of IL-2 is reduced, or treatment is stopped entirely, if the side effects become severe. This analysis includes the total number of doses taken at the end of Cycle 4, by all participants who began the trial, regardless of how many cycles each participant completed.
Measured: Cycle 4 (up to 12 weeks of IL-2 treatment)
Secondary outcomes (5)
Plasma Concentrations of Adrenocorticotropic Hormone (ACTH)
Adrenocorticotropic hormone (ACTH) is a stress hormone that is synthesized by the pituitary in response to corticotropin-releasing hormone (CRH). ACTH stimulates adrenal cortisol production. ACTH levels vary throughout the day and are highest between 6am and 8am. A typical reference range is 10-50 picograms per milliliter (pg/ml) from blood drawn in the morning. Low levels of ACTH can indicate adrenal insufficiency (including adrenal cancers) while high levels may indicate several diseases or stress. IL-2 treatment stimulates the release of ACTH and this stimulation is dose dependent (rising as the dose of IL-2 increases) and tends to increase further with repeated exposure to IL-2. Blood was drawn for measuring ACTH at screening (baseline value) and once during days 1-3 of each cycle of the four IL-2 treatments.
Measured: Screening and Cycles 1 - 4 (up to 14 weeks)
Plasma Concentrations of Interleukin 6 (IL-6)
Immune system functioning was assessed by measuring plasma concentrations of interleukin 6 (IL-6). IL-6 is a proinflammatory cytokine that is elevated during times of inflammation, infection, in patients with advanced or metastatic cancer, and is also implicated in mood disorders. IL-2 treatments are associated with increased IL 6 levels, in a dose response manner. IL-6 values in healthy individuals are generally less than 16 pg/ml. Blood was drawn for measuring IL-6 at screening (baseline value) and once during days 1-3 of each cycle of the four IL-2 treatments.
Measured: Screening and Cycles 1 - 4 (up to 14 weeks)
Plasma Concentrations of Cortisol
Cortisol is a steroid hormone made in the adrenal glands in response to fear or stressful situations. A typical reference range is 6-23 micrograms/deciliter (mcg/dL) from blood drawn in the morning. Low levels of cortisol can indicate Addison's disease or a problem with the pituitary gland, while high levels may indicate tumors of the adrenal gland, among other illnesses, or increased stress. Chronic elevation of cortisol is associated with reduced immune function and increased risk of heart disease. IL-2 treatment stimulates the release of cortisol and this stimulation is dose dependent (rising as the dose of IL-2 increases) and tends to increase further with repeated exposure to IL-2. Blood was drawn for measuring cortisol at screening (baseline value) and once during days 1-3 of each cycle of the four IL-2 treatments.
Measured: Screening and Cycles 1 - 4 (up to 14 weeks)
Hamilton Depression Rating Scale (HAM-D) Score
Hamilton Depression Rating Scale (HAM-D) is a 21-item, observer-rated scale which quantifies the severity of depressive symptoms, including depressed mood, loss of interest in usually pleasurable activities, insomnia, anorexia, fatigue, weight loss, and psychomotor retardation or agitation. Participants rate the severity of their symptoms on a scale of 0-2 or 0-4 (depending on the item), where 0 means that the symptom is absent. Total scores are calculated by summing the first 17 items for a total score between 0 and 50. For this study a score of 0-6 indicates a normal state, a score of 7-17 indicates mild depression, a score of 18-24 indicates moderate depression, and a score of greater than 25 indicates severe depression. The HAM-D was administered at screening (baseline value) and once during days 1-3 of each cycle of the four IL-2 treatments.
Measured: Screening and Cycles 1 - 4 (up to 14 weeks)
Genetic Polymorphisms
Measured: Screening and After Cycle 4 (up to 14 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2006 (estimated)
- Study start6 Oct 2006
- Primary completion17 May 2010
- Study completion17 May 2010
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.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Andrew H Miller, Emory University
- Investigators
- Dominique L. Musselman, MD,MS, Principal investigator, Emory UniversityDavid Lawson, MD, Study chair, Emory UniversityAndrew Miller, MD, Study chair, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00352885
- Sponsor's protocol ID
- IRB00024759
- Other IDs
- R01MH071580, DATR A3-NSS
- Status last verified
- Aug 2018
- First submitted
- 13 Jul 2006
- Last updated
- 14 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 23575741Vita G, Compri B, Matcham F, Barbui C, Ostuzzi G. Antidepressants for the treatment of depression in people with cancer. Cochrane Database Syst Rev. 2023 Mar 31;3(3):CD011006. doi: 10.1002/14651858.CD011006.pub4.
PubMed 36999619McNutt 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.
PubMed 22353759
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- IL-2 Neuropsychiatric Symptoms: Mechanism and Prevention
- ClinicalTrials.gov ID
- NCT00352885
- Acronym / sponsor ID
- IRB00024759
- Conditions
- Depression
- Keywords
- Cancer, IL-2 therapy, Antidepressant, Immune system, Neuroendocrine response
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 6 Oct 2006 (actual)
- Primary completion
- 17 May 2010 (actual)
- Study completion
- 17 May 2010 (actual)
- First posted
- 17 Jul 2006 (estimated)
- Results
- Posted 27 Jun 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Escitalopram | Experimental | Drug: Escitalopram, Drug: IL-2Participants will receive escitalopram and IL-2 treatment |
| Placebo | Placebo comparator | Drug: Placebo, Drug: IL-2Participants will receive placebo and IL-2 treatment |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Diagnosed with cancer and beginning Interleukin (IL)-2 treatment
- Willing to use an effective form of birth control throughout the study if sexually active
Key exclusion criteria (13 listed)
- 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
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 |
|---|---|---|
| EscitalopramAlso: LexaproParticipants 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. | Drug | Escitalopram |
| PlaceboAlso: Sugar pillParticipants 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. | Drug | Placebo |
| IL-2IL-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. | Drug | Escitalopram, Placebo |
Primary outcome
Number of IL-2 Treatments Tolerated
Time frame: Cycle 4 (up to 12 weeks of IL-2 treatment)
The mean number of IL-2 doses tolerated (out of the possible 60 total doses) are presented for each study arm. The standard high dose regimen of IL-2 includes 15 doses per cycle. The dose of IL-2 is reduced, or treatment is stopped entirely, if the side effects become severe. This analysis includes the total number of doses taken at the end of Cycle 4, by all participants who began the trial, regardless of how many cycles each participant completed.
5 secondary outcomes
Plasma Concentrations of Adrenocorticotropic Hormone (ACTH)
Time frame: Screening and Cycles 1 - 4 (up to 14 weeks)
Plasma Concentrations of Interleukin 6 (IL-6)
Time frame: Screening and Cycles 1 - 4 (up to 14 weeks)
Plasma Concentrations of Cortisol
Time frame: Screening and Cycles 1 - 4 (up to 14 weeks)
Hamilton Depression Rating Scale (HAM-D) Score
Time frame: Screening and Cycles 1 - 4 (up to 14 weeks)
Genetic Polymorphisms
Time frame: Screening and After Cycle 4 (up to 14 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23575741Musselman 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.
- Derived from this study: PubMed 36999619Vita G, Compri B, Matcham F, Barbui C, Ostuzzi G. Antidepressants for the treatment of depression in people with cancer. Cochrane Database Syst Rev. 2023 Mar 31;3(3):CD011006. doi: 10.1002/14651858.CD011006.pub4.
- Derived from this study: PubMed 22353759McNutt 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.
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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.
Dominique L. Musselman, MD,MS principal investigator
Emory University
David Lawson, MD study chair
Emory University
Andrew Miller, MD study chair
Emory University
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 and IL-2 in people with Depression, run by Emory University 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 2 inclusion and 13 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 14 Sep 2018. 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 27 Jun 2014). 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?
Number of IL-2 Treatments Tolerated (time frame: Cycle 4 (up to 12 weeks of IL-2 treatment)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00352885, which also lists 3 linked publications.
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 14 Sep 2018.