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Methylphenidate for Depressed Cancer Patients Receiving Palliative Care

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ClinicalTrials.gov Identifier: NCT00129467
Recruitment Status : Completed
First Posted : August 11, 2005
Results First Posted : February 12, 2014
Last Update Posted : April 24, 2015
Sponsor:
Collaborator:
Oregon Health and Science University
Information provided by (Responsible Party):
VA Office of Research and Development ( US Department of Veterans Affairs )

Tracking Information
First Submitted Date  ICMJE August 9, 2005
First Posted Date  ICMJE August 11, 2005
Results First Submitted Date  ICMJE October 16, 2013
Results First Posted Date  ICMJE February 12, 2014
Last Update Posted Date April 24, 2015
Study Start Date  ICMJE February 2005
Actual Primary Completion Date September 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 20, 2013)
Days to Remission of Depression [ Time Frame: 18 Days ]
Days to a 50% or greater reduction in initial Montgomery-Asberg Depression Rating Scale (MADRS) score.
Original Primary Outcome Measures  ICMJE
 (submitted: August 9, 2005)
  • We'll use the clinician-rated Montgomery-Asberg Depression Rating Scale (MADRS) to measure changes in depression over the 18-day study period.
  • To measure improvement in depression we will use the depression subscale of the Hospital Anxiety and Depre
Change History Complete list of historical versions of study NCT00129467 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: August 9, 2005)
  • We'll determine the degree to which depression improvement is mediated by pain improvement by using the Wisconsin Brief Pain Inventory (WBPI) short version.
  • The measure of the quality of life of patients at the end of life (QUAL-E) was chosen to help
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Methylphenidate for Depressed Cancer Patients Receiving Palliative Care
Official Title  ICMJE Methylphenidate for Depressed Cancer Patients in Hospice
Brief Summary The purpose of this study is to determine whether methylphenidate is an effective treatment for depression and to document the safety and tolerability of methylphenidate in combination with an Selective Serotonin Reuptake Inhibitor (SSRI) in SSRI treated, terminally ill, hospice and palliative care cancer patients. The investigators hypothesize that depressed hospice and palliative care patients will be more likely to have a 50% reduction in scores on a clinical measure of depression after treatment with Methylphenidate plus an SSRI compared to those patients who are taking a placebo plus an SSRI.
Detailed Description

Background: Major depressive disorder can be diagnosed in between 5% and 26% of terminally ill patients. This disorder causes suffering, and is associated with suicidality, increased pain, and increased caregiver burden and caregiver depression. Treatment of depression in cancer patients in hospice and palliative care is complicated by shortened life expectancy. Currently-approved antidepressants take several weeks to be effective. Methylphenidate has been reported in case series and very small randomized trials in patients without cancer as a rapidly effective treatment for depression in medically ill patients. There are no randomized controlled trials to test this agent in terminally ill cancer patients.

Objectives: (1) To determine the effectiveness and safety of methylphenidate for depression treatment in cancer patients receiving hospice and palliative care, (2) to explore whether successful treatment of depression is associated with improved quality of life, and (3) to explore whether effective treatment of depression influences caregiver depression and caregiver burden.

Methods: We will conduct an 18-day randomized, double-blind, fixed-dose (10 mg bid), placebo-controlled clinical trial of methylphenidate for depression in eligible veteran and non-veteran cancer patients with advanced cancer in the following settings: inpatient and outpatient hospice, inpatient and outpatient palliative care, and inpatient and outpatient cancer clinics. We will determine whether improvement in depression is mediated by decreased pain and document the safety and tolerability of methylphenidate in these patients. We will explore whether improvement in depression results in improved quality of life for these patients, and decreases caregiver depression and burden.

Eligible patients who answer yes to the question "are you sad or depressed" will be invited to participate. They will complete measures of depression [Structured Clinical Interview for Diagnosis (SCID), Montgomery-Asberg Depression Rating Scale (MADRS) as primary outcome, Hospital Anxiety and Depression Scale (HADS) as secondary outcome], quality of life, pain, and cognition at baseline. MADRS scores must be greater than 19 and SCID positive for depression at study entry. Subjects will be randomized to either methylphenidate plus an SSRI, or placebo plus an SSRI. Subjects may continue any previously prescribed SSRI, or will be prescribed citalopram if untreated. Participants will be evaluated with the same measures as baseline on days 3, 6, 12 and 18 of the study. In an open label portion of the study, methylphenidate-treated patients whose depression has improved will be followed up to 2 months. Cox proportional hazard analysis will be used to analyze the primary outcome. An estimated 104 subjects will be entered over five years. Caregivers will complete measures of depression and caregiver burden at days 0 and 18.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Depression
  • Palliative Care
  • Cancer
  • Mental Disorder
Intervention  ICMJE
  • Drug: Methylphenidate

    Subjects will take methylphenidate 5 mg twice daily (bid) for 3 days, then 10 mg bid for the remainder of the study. Should a subject have a 50% decrease in their depressive symptoms as measured by the Montgomery Asberg Depression Rating Scale (MADRS) at the initial dose of methylphenidate, they will be maintained at that lower dose as long as their MADRS score remains reduced by 50%. During the 18-day blinded treatment period the total daily dose will not exceed 20 mg.

    If subjects have side effects when increasing to 10 mg bid, they will drop back to 5 mg bid. If the participant develops psychosis or cardiac events, they will be discontinued from methylphenidate.

    Subjects who receive methylphenidate and respond with a 50% reduction in MADRS score will have the option to continue in the open label portion of the study for up to 6 weeks. For patients taking methylphenidate 10 mg bid whose MADRS score is > 10 at day 18, the dose may be increased to 15 mg bid.

    Other Name: Ritalin
  • Drug: Placebo

    Subjects assigned to placebo will receive 1 capsule of placebo twice per day (bid) for 3 days and then 2 capsules bid for the remainder of the study. Should a subject have a 50% decrease in their depressive symptoms as measured by the Montgomery Asberg Depression Rating Scale (MADRS) at the initial dose of placebo, they will be maintained at that lower dose as long as their MADRS score remains reduced by 50%.

    If subjects have side effects when increasing the dose to 2 capsules bid, they will drop back to 1 capsule bid. If the participant develops psychosis or cardiac events, they will be discontinued from the intervention.

  • Drug: Selective Serotonin Uptake Inhibitor (SSRI)

    Each subject will be treated with a SSRI. Patients who are taking an SSRI at the time of enrollment will continue on the same medication during the 18-day blind treatment period. The prescribed dose will only be adjusted if it is more than the highest dose in the recommended range (fluoxetine to 40 mg, paroxetine to 40 mg, citalopram to 40 mg, sertraline to 150 mg). Patients who are not on a SSRI at the time of enrollment will be prescribed citalopram 10 mg per day for 2 weeks, then 20 mg per day.

    A subject's SSRI may be discontinued if the subject experiences moderate to severe side effects likely attributable to a SSRI. If subjects experience similar symptoms when increasing their citalopram dose to 20 mg per day, they will drop back to 10 mg per day. During the open label extension, the SSRI may be increased, decreased, or changed to a different SSRI or other antidepressant with the exception of venlafaxine and bupropion

    Other Name: Celexa
Study Arms  ICMJE
  • Experimental: methylphenidate + SSRI
    During the 18-day blind treatment period, subjects will be prescribed methylphenidate 5-10 mg twice per day and selective serotonin reuptake inhibitor (SSRI). Subjects already receiving a SSRI when they begin the study, will continue on the recommended dose of that SSRI; subjects not receiving a SSRI will be prescribed 10-20 mg per day Citalopram. Subjects who respond to methylphenidate treatment will have the option of continuing on methylphenidate, up to 15 mg bid, and an antidepressant in the 6 week open label portion of the study.
    Interventions:
    • Drug: Methylphenidate
    • Drug: Selective Serotonin Uptake Inhibitor (SSRI)
  • Placebo Comparator: Placebo + SSRI
    During the 18-day blind treatment period, subjects will be prescribed placebo 1-2 capsules twice per day and selective serotonin reuptake inhibitor (SSRI). Subjects already receiving a SSRI when they begin the study, will continue on the recommended dose of that SSRI; subjects not receiving a SSRI will be prescribed 10-20 mg per day Citalopram.
    Interventions:
    • Drug: Placebo
    • Drug: Selective Serotonin Uptake Inhibitor (SSRI)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 20, 2013)
47
Original Enrollment  ICMJE
 (submitted: August 9, 2005)
104
Actual Study Completion Date  ICMJE December 2010
Actual Primary Completion Date September 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Inclusion:

  • Either enrolled in the OHSU radiology/oncology clinic or VA palliative care, and living within 120 miles of the Portland VAMC.
  • Life-limiting disease is any type of solid or blood cancer.
  • Eighteen years of age or older.
  • Life expectancy of 1 year or less as reflected by hospice admission or palliative care status. Although exact life expectancy can not be predicted, actively dying patients with estimated life expectancy of < 10 days are unlikely to be enrolled.
  • Diagnosis of major depression disorder as determined by the Structured Clinical Interview for Diagnosis (SCID).
  • Significant depressive cognitive symptomatology as determined by a MADRS greater than 19.
  • Currently taking an SSRI but still depressed enough to meet eligibility criteria or not taking SSRI but depressed enough to start on SSRI.
  • Willing and able to give informed consent to participate in this study as demonstrated by the MacArthur Competence Assessment Tool for clinical research.
  • Speaks/understands English.
  • For patients at home who cannot self-administer medications, has a caregiver who can assist with administering medication.

Exclusion Criteria:

Exclusion:

  • Dementia or Delirium as determined by the Short Portable Mental Status Questionnaire (SPMSQ) score of less than 7.
  • Diagnosis of delirium as determined by the Confusional Assessment Method (CAM).
  • Any of the following Brief Psychiatric Rating Scale (BPRS) items rated 4 -, elated mood, suspiciousness, hallucinations, excitement, distractibility or motor hyperactivity.
  • Severe insomnia.
  • Severe anxiety.
  • Significant suicidal ideation.
  • History of current mental disorder in which depressive symptoms occur, but for which psychostimulants are contraindicated (schizophrenia and bipolar disorder will be based on history; active psychotic symptoms on selected BPRS items).
  • History of stimulant abuse or other active, severe substance abuse.
  • Contraindications to methylphenidate or an SSRI including significant cardiac arrhythmias; uncontrolled, severe hypertension; moderate-severe angina; seizure disorder; severe COPD; use of medications such as Levodopa, monoamine oxidase inhibitors, and lithium; diagnosis of narrow-angle glaucoma; or history of SSRI-induced hyponatremia,.
  • Physical symptoms including increased blood pressure (DBP greater than 115, SBP greater than 180), pulse greater than 120, irregular pulse, or chest pain consistent with angina.
  • Treatment for depression with a non-SSRI antidepressant including Bupropion and Venlafaxine during protocol.
  • Known serum creatinine > 3.0, or severe liver disease as reflected by jaundice or hepatic encephalopathy.
  • Unable to swallow pills, however if patient has gastrostomy tube or feeding tube in place the study medicines may be administered by this route. Pills may be poured into food.
  • Receiving hospice care in a skilled nursing facility.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00129467
Other Study ID Numbers  ICMJE IIR 03-194
01153 ( Other Identifier: Portland VAMC IRB )
10-0603 ( Other Identifier: Portland VAMC R&D )
CPC-04115-LX ( Other Identifier: OHSU Knight Cancer Institute )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party VA Office of Research and Development ( US Department of Veterans Affairs )
Study Sponsor  ICMJE US Department of Veterans Affairs
Collaborators  ICMJE Oregon Health and Science University
Investigators  ICMJE
Principal Investigator: Linda K. Ganzini, MD MPH VA Portland Health Care System, Portland, OR
PRS Account VA Office of Research and Development
Verification Date August 2013

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