Study of Methylphenidate as Add on Therapy in Depressed Cancer Patients

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2011 by University of Malaya.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Dr Ng Chong Guan, University of Malaya
ClinicalTrials.gov Identifier:
NCT01497548
First received: February 24, 2011
Last updated: December 21, 2011
Last verified: December 2011
  Purpose

Primary Objective To determine the efficacy of Methylphenidate as add on therapy to mirtazapine in the treatment of depression in cancer patients under palliative care Hypothesis Methyphenidate add on to mirtazapine treated subjects will show significant early reduction in (Montgomery Asberg Depression Rating Scale) MADRS between baseline and Day 3.

Secondary Objective

  1. To determine the efficacy of Methylphenidate as add on therapy to mirtazapine in the treatment of anxiety in cancer patients under palliative care.

    Hypothesis Methyphenidate add on to mirtazapine treated subjects will show significant early reduction in anxiety score of HADS than Mirtazepine alone treated subjects between baseline and Day 3.

  2. To determine the efficacy of Methylphenidate as add on therapy to mirtazapine in reducing distress in cancer patients under palliative care.

    Hypothesis Methyphenidate add on to mirtazapine treated subjects will show significant early reduction in distress score of distress thermometer than Mirtazepine alone treated subjects between baseline and Day 3.

  3. To determine the efficacy of Methylphenidate as add on therapy to mirtazapine in improving function in cancer patients under palliative care.

    Hypothesis Methyphenidate add on to mirtazapine treated subjects will show increase in the (Eastern Cooperation Group performance status) ECOG score than Mirtazepine alone treated subjects between baseline and Day 3

  4. To determine the efficacy of Methylphenidate as add on therapy to mirtazapine in reducing somatic complaints in cancer patients under palliative care.

Hypothesis Methyphenidate add on to mirtazapine treated subjects will show significant early reduction in the score of Numeric Rating Scale (NRS) for Pain and Visual Analogue Scale (VAS) for Fatigue than Mirtazapine alone treated subjects between baseline and Day 3.


Condition Intervention Phase
Depression
Drug: Methylphenidate
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Parallel-group, Double-blind, Placebo-controlled Study of Methylphenidate as an Add on Therapy for Mirtazapine in the Treatment of Major Depressive Disorder in Cancer Patients Under Palliative Care

Resource links provided by NLM:


Further study details as provided by University of Malaya:

Primary Outcome Measures:
  • depressive symptoms [ Time Frame: 3 to 28 days ] [ Designated as safety issue: No ]
    measured with Montgomery-Åsberg Depression Rating Scale


Secondary Outcome Measures:
  • Distress level [ Time Frame: 3 to 28 days ] [ Designated as safety issue: No ]
    Measured with distress thermometer


Estimated Enrollment: 120
Study Start Date: March 2011
Estimated Study Completion Date: October 2012
Estimated Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Methylphenidate add on to Mirtazapine
Methylphenidate add on to the usual treatment (Mirtazapine)
Drug: Methylphenidate
Methylphenidate started at 5mg on morning (0800) and noon (1200) on day 1. Dose increased to 10mg on morning (0800) and noon (1200) on day 3; 15mg on morning and noon on day 6 depending on the clinical response. Similarly, the dose can be reduced to 5mg/day if patients are not able to tolerate a higher dose. The treatment continues until day 28.
Other Name: Ritalin
Placebo Comparator: Placebo add on to Mirtazapine
Non active compund add on to the usual treatment (Mirtazapine)
Drug: Placebo
Placebo given on morning (0800) and noon (1200)daily
Other Name: Non active compound

  Hide Detailed Description

Detailed Description:

Background

Cancer remains one of the most feared illnesses and the diagnosis of cancer has huge psychological impact on the patients and their care-takers (Knobf, 2007). Depression is one the most common psychiatric sequella (Derogatis et al., 1983)2 and affects the quality of life, compliance to treatment, disease advancement, tolerability to pain and fatigue in cancer patients (Bennett et al., 2004; Sommerset, 2004; Green et al., 2009). However, it is likely that depression is under-recognized and under-treated in cancer patients (Kadan-Lottick et al., 2005).

Depressed feelings manifest in a spectrum ranging from normal sadness to a variety of mood disturbances and clinical presentations. It is challenging to differentiate clinical depression from "normal" emotional distress in cancer patients and the somatic symptoms such as fatigue, loss of appetite or weight, sleep difficulties, poor memory and concentration may mirror the physiological symptoms caused by cancer or its treatment (McDaniel and Musselman, 1995; Masie and Popkin, 1998; Cochinov, 2001; Jesse et al., 2008). This complicates the diagnosis of depression in cancer patients (McDaniel and Musselman, 1995; Masie and Popkin, 1998; Cochinov, 2001; Pasquini and Biond, 2007; Jesse et al., 2008).

Many studies have investigated the prevalence of depression in cancer in the past decades. A previous review by Mc Daniel et al, reported a prevalence of major depression ranging from 4.8% to 9.2% based on studies using standardized diagnostic interviews on cancer outpatients. Prevalence rates were higher in the admitted cancer patients (8% for Major Depression and 15% to 36% for all depressive disorders)(McDaniel and Musselman, 1995). A preliminary systematic review on the prevalence of depression in cancer patients was conducted by the investigator of this study. It showed that major depressive disorder was as high as 10.8% in cancer patients based on structured clinical interview.

In addition to the high prevalence, uncertainty exists with respect to the optimal treatment of depression in cancer. Although a huge number of studies investigated the efficacy of pharmacotherapy for depression in general population, the number of randomized, controlled trials of antidepressants on depression in cancer patient conducted is limited(Challman and Lipsky, 2000; Raison and Miller, 2003). A comprehensive systematic review looking into the effectiveness and tolerability of antidepressant treatment in depressed cancer patients was performed and published by Rodin et al in 2007. Although 7 trials were identified, the authors commented that the number of positive randomized trials was limited and there is a need for more rigorous studies on other newer agents or alternative treatment option (Raison and Miller, 2003). The preliminary systematic review conducted by the investigator of this study also came to the same conclusion.

Psychostimulants such as methylphenidate have been proposed for the treatment of depressed patients because of their rapid onset of action (Masand and Tesar, 1995; Challman and Lipsky, 2000; Rozans et al., 2002; Kaminski and Sjogren, 2007). They may have antidepressant effects and may be advantageous due to the rapid onset of action (Candy et al., 2008). Some studies suggest they provide a safe and effective treatment of depression in cancer patients (Masand and Tesar, 1995) and alleviates opioid induced somnolence, improve cognitive function and ameliorate pain in cancer patients. Another potential advantage of the use of psychostimulant in the cancer patients is the ability to improve multiple somatic symptoms irrespective of the etiology (Vigano et al., 1995). However, the number of studies looking into the efficacy of psychostimulant in improving depressive mood in cancer is limited.

Five studies were identified from the review conducted by the investigator of this study. Although they showed positive result on the use of methylphenidate in depressed cancer patients, they were open-label and without control group. There is only one double blind, randomised placebo controlled study on the use of methylphenidate in cancer patients which was published in French language (Laval, 2008).Considering the lack of randomized controlled trial on the topic, the need of study on the efficacy and tolerability of psychostimulant such as methylphenidate as an add on therapy of depression in cancer patients is inevitably needed.

Primary Objective To determine the efficacy of Methylphenidate as add on therapy to mirtazapine in the treatment of depression in cancer patients

Secondary Objective

  1. To determine the efficacy of Methylphenidate as add on therapy to mirtazapine in the treatment of anxiety in cancer patients.
  2. To determine the efficacy of Methylphenidate as add on therapy to mirtazapine in reducing distress in cancer patients.
  3. To determine the efficacy of Methylphenidate as add on therapy to mirtazapine in improving function in cancer patients.
  4. To determine the efficacy of Methylphenidate as add on therapy to mirtazapine in reducing somatic complaints in cancer patients.

Study Design

Design An open label, parallel group, placebo controlled study on methylphenidate as add on therapy to mirtazapine.

Procedure Subjects will be male or female with current diagnosis of cancer of any types and DSM-IV diagnoses of major depressive disorder. They are identified from the oncology, surgical and palliative clinics and wards. Depressive symptoms will be measured at screening with the MADRS.

Sixty (120) subjects will be recruited and started on the mirtazapine 30mg at night. They will be then randomized to one of two groups (60 subjects per group): Methylphenidate or Placebo as add on therapy. All treatment will be initiated after screening and continued for 28 days of outpatient or inpatient treatment. Efficacy evaluation will be take place at baseline, day 3, day 6, 9, 14, 21 and day 28.

At the end of the 28 days, the continuation of treatment will be depends on the investigator's clinical judgment and End of Medication Evaluation will be perform. Every effort will be made to continue to evaluate all subjects who are randomized even if they decide to discontinue the medication.

Project Timetable The project will take 2 years. The plan is to randomize 2 subjects per week, taking about 15 month to acquire 120 subjects. All subjects will have completed study drug treatments before 18 months have elapsed. Follow-up evaluations will be completed 2 year from the start of the project.

Primary Study Endpoints

The primary endpoints to be measured in this study are:

- MADRS at the baseline, Day 3, 6, 9, 14, 21 and 28.

Secondary Study Endpoints

The secondary endpoints to be measured are:

  • Anxiety with HADS at baseline, Day 3, 6, 9, 14, 21 and 28
  • Distress score with distress thermometer at baseline, Day 3, 6, 9, 14, 21 and 28
  • Karnofsky Scale at the baseline, Day 3, 6, 9, 14, 21 and 28
  • Numeric Rating Scale (NRS) for Pain at the baseline, Day 3, 6, 9, 14, 21 and 28
  • Visual Analogue Scale (VAS) for Fatigue at the baseline, Day 3, 6, 9, 14, 21 and 28

Primary Safety Endpoints The primary safety endpoint will be measurement and collection of any serious adverse event that occurs from initial study treatment through and including 14 days after cessation of study treatment.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female, aged >18 years.
  2. Current DSM IV diagnosis of Major Depressive Disorder.
  3. Under palliative care.
  4. Confirmed diagnosis of cancer.
  5. Not on any antidepressants

Exclusion Criteria:

  1. Clinical significant abnormal laboratory values.
  2. Clinically significant abnormal ECG.
  3. Documented history of other psychiatric diagnosis (schizophrenia, bipolar disorder, organic brain disorder, dementia etc.)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01497548

Contacts
Contact: Chong Guan Ng, MBBS, MPM 60379604367 chong_guan@hotmail.com

Locations
Malaysia
University Malaya Medical Centre Not yet recruiting
Kuala Lumpur, Malaysia, 59100
Contact: Chong Guan Ng, MBBS, MPM    60379604367    chong_guan@hotmail.com   
Principal Investigator: Chong Guan Ng, MBBS, MPM         
University Malaya Medical Centre Recruiting
Kuala Lumpur, Malaysia, 50603
Contact: Chong Guan Ng, MBBS, MPM    0379492068    chong_guan1975@yahoo.co.uk   
Sponsors and Collaborators
University of Malaya
Investigators
Principal Investigator: Chong Guan Ng, MBBS, MPM Department of Psychological Medicine, University Malaya Medical Centre
  More Information

Publications:

Responsible Party: Dr Ng Chong Guan, Principal Investigator, University of Malaya
ClinicalTrials.gov Identifier: NCT01497548     History of Changes
Other Study ID Numbers: NCG001
Study First Received: February 24, 2011
Last Updated: December 21, 2011
Health Authority: Malaysia: Medical Ethical Comittee, University Malaya Medical Centre

Keywords provided by University of Malaya:
Depression
cancer
methylphenidate
pharmacotherapy

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders
Methylphenidate
Mirtazapine
Dopamine Uptake Inhibitors
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Neurotransmitter Uptake Inhibitors
Physiological Effects of Drugs
Central Nervous System Stimulants
Central Nervous System Agents
Therapeutic Uses
Antidepressive Agents, Tricyclic
Antidepressive Agents
Psychotropic Drugs
Histamine H1 Antagonists
Histamine Antagonists
Histamine Agents
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents

ClinicalTrials.gov processed this record on July 10, 2014