<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03254173</url>
  </required_header>
  <id_info>
    <org_study_id>MCACS100</org_study_id>
    <nct_id>NCT03254173</nct_id>
  </id_info>
  <brief_title>Mirtazapine for Treatment of Cancer Associated Anorexia-cachexia</brief_title>
  <acronym>MCACS100</acronym>
  <official_title>Mirtazapine for Treatment of Cancer Associated Anorexia-cachexia : a Randomized Controlled Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Catherine Naseef Hunter</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Kasr El Aini Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      A randomized controlled clinical trial will be conducted to assess the efficacy of the FDA&#xD;
      approved drug , mirtazapine , in treatment of cancer associated anorexia cachexia syndrome.&#xD;
&#xD;
      Two arms will be compared . Arm A will involve 50 patients with confirmed advanced cancer&#xD;
      receiving mirtazapine 15 mg once daily for 8 weeks &amp; Arm B will involve another 50 patients&#xD;
      with confirmed advanced cancer receiving placebo for 8 weeks.&#xD;
&#xD;
      Both arms will be compared to assess efficacy of mirtazapine in appetite stimulation&#xD;
      primarily and to assess other outcomes secondarily which will be discussed later in details.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      -  A Written consent is to be obtained from all patients before being enrolled in the&#xD;
           study.&#xD;
&#xD;
        -  Baseline Complete Blood Count , Liver function tests and kidney function tests will be&#xD;
           obtained to assess safety to start the drug and to assess its dose adjustment.&#xD;
&#xD;
        -  Two arms will be compared : mirtazapine oral 15mg daily versus placebo. This will be&#xD;
           conducted on a double-blinded basis.&#xD;
&#xD;
        -  Oral mirtazapine ( REMERON , RD , 30 mg tablets , Organon ) will be the original FDA&#xD;
           approved drugs that will be used in the study.&#xD;
&#xD;
        -  Treatment allocation will be concealed from patients, investigators, and study&#xD;
           coordinators enrolling the participants.&#xD;
&#xD;
        -  All patients will be counseled and given dietary advice by a dietician at baseline.&#xD;
&#xD;
        -  Patients will be permitted to continue treatment at the same dose as scheduled as long&#xD;
           as weight was stabilized (no loss greater than 10 % of body weight at baseline).&#xD;
&#xD;
        -  Duration of therapy : Patients will remain on protocol for a duration of 8 weeks as long&#xD;
           as they did not develop serious concurrent illness preventing further treatment,&#xD;
           unacceptable adverse events (grade 3 or higher), the patient decides to withdraw from&#xD;
           study, or the investigator judges that it is in the patient's best interest to&#xD;
           discontinue treatment due to general or specific health conditions.&#xD;
&#xD;
        -  Demographic data will include performance status, tumor type, sex, age, and percentage&#xD;
           weight loss.&#xD;
&#xD;
        -  The ESAS scale (Edmonton Symptom Assessment Scale ) will be used to assess the following&#xD;
           10 symptoms experienced by patients with cancer during the previous 24 hours:&#xD;
&#xD;
             1. pain.&#xD;
&#xD;
             2. Fatigue.&#xD;
&#xD;
             3. Nausea.&#xD;
&#xD;
             4. Depression.&#xD;
&#xD;
             5. Anxiety.&#xD;
&#xD;
             6. Drowsiness.&#xD;
&#xD;
             7. Dyspnea.&#xD;
&#xD;
             8. Anorexia.&#xD;
&#xD;
             9. Sleep disturbance.&#xD;
&#xD;
            10. And feelings of well-being.&#xD;
&#xD;
      The severity of each symptom is rated on a numerical scale of 0 to 10 (0_no symptom, 10_worst&#xD;
      possible severity). The ESAS is both valid and reliable in the assessment of the intensity of&#xD;
      symptoms in patients with cancer.&#xD;
&#xD;
        -  The FAACT questionnaire ( Functional Assessment of Anorexia\Cachexia Therapy ) with&#xD;
           anorexia \ cachexia subscale will be used to assess quality of life among the studied&#xD;
           patients , in a form of questionnaire including :&#xD;
&#xD;
             1. Physical well-being.&#xD;
&#xD;
             2. Social well-being.&#xD;
&#xD;
             3. Emotional well-being.&#xD;
&#xD;
             4. Functional well-being.&#xD;
&#xD;
             5. Additional concerns.&#xD;
&#xD;
                The patient rates the answer on a scale of 0 to 4. The FACIT - Pal scale is&#xD;
                internally consistent , reliable and valid as a measure of health-related quality&#xD;
                of life for persons with advanced cancer.&#xD;
&#xD;
                We will contact their website to get the licence to use the questionnaire and to&#xD;
                get its translated version.&#xD;
&#xD;
        -  Anthropometric measures to assess efficacy of mirtazapine in weight gain :&#xD;
&#xD;
             1. Assessment of weight of the patient .&#xD;
&#xD;
             2. Assessment of muscle strength ( via hand grip dynamometry , using the device named&#xD;
                Lite 200 lb , Fabrication Enterprises Incorporated Company).&#xD;
&#xD;
             3. Assessment of lean ( via bioimpedance analysis , using the device named BF100 ,&#xD;
                Beurer Company ).&#xD;
&#xD;
        -  Biological methods to assess efficacy of mirtazapine in modulating inflammatory cytokine&#xD;
           media : quantitative c-reactive protein (CRP) and comparative analysis by enzyme-linked&#xD;
           immunoassay (ELISA) will be performed on IL-6 ( Interleukin - 6 ) , and YKL-40 serum&#xD;
           levels according to availability. They will be obtained at baseline (day 1 of treatment,&#xD;
           immediately before first dose) and at week 8.&#xD;
&#xD;
        -  Evaluation of safety and tolerability Patients who will receive at least one dose of&#xD;
           study medication will be done.&#xD;
&#xD;
        -  A traditional definition of dose-limiting toxicity (DLT) within the first cycle Will be&#xD;
           used (any grade 3 non-hematologic or grade 4 hematologic toxicity within 4 weeks and&#xD;
           assessed as being at least possibly related to study drug).&#xD;
&#xD;
        -  A toxicity questionnaire will be done at baseline and then at 14-day intervals until day&#xD;
           28.&#xD;
&#xD;
      To fully assess the toxicity profile of the drug, the safety evaluation period in the trial&#xD;
      will be extended 30 days from the date of the last dose of study drug.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 26, 2018</start_date>
  <completion_date type="Actual">October 17, 2019</completion_date>
  <primary_completion_date type="Actual">October 17, 2019</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>double-blinded randomized controlled trial.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>Treatment allocation will be concealed from patients, investigators, and study coordinators enrolling the participants.&#xD;
The pills used in the study ( either remeron or placebo ) will be kept into opaque containers , in order to be concealed from patients , investigators and study coordinators.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Efficacy of mirtazapine in appetite stimulation in patients with cachexia due to advanced cancer with a change of increase of 1.5 degree on a numerical scale of 0 -10 as a target .</measure>
    <time_frame>It will be assessed at week 4 of receiving the intervention. The 4-week duration of treatment is of sufficient length to obtain benefit from an effective intervention for appetite.</time_frame>
    <description>Efficacy of mirtazapine in appetite stimulation in patients with cachexia due to advanced cancer with a change of increase 1.5 degree on a scale of 0-10 as a target , where 0 represents minimum appetite and 10 represents maximum appetite.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Efficacy of mirtazapine in weight gain. ''Improved'' weight will be defined as a gain of ≥ 1 kg and ''maintained weight'' will be defined as a loss of &lt;500 g, or a gain of &lt;1 kg.</measure>
    <time_frame>It will be assessed at week 8 of receiving the intervention.</time_frame>
    <description>Efficacy of mirtazapine in weight gain in patients with cachexia due to advanced cancer.''Improved'' weight will be defined as a gain of ≥ 1 kg and ''maintained'' will be defined as a loss of &lt;500 g, or a gain of &lt;1 kg.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of mirtazapine in improving other symptoms , such as : nausea , vomiting , sleep with a change of decrease of ≥ 2 points on the ESAS ( Edmonton Symptom Assessment Scale ) from baseline.</measure>
    <time_frame>It will be assessed at week 8 of receiving the intervention.</time_frame>
    <description>Effect of mirtazapine in improving other symptoms , such as : nausea , vomiting , sleep in patients with cachexia due to advanced cancer with a change of decrease of ≥ 2 points on the ESAS scale from baseline. The ESAS is both valid and reliable in the assessment of the intensity of symptoms in patients with cancer.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of mirtazapine in improving quality of life : will be measured by an increase of 16 points in the FAACT questionnaire ( Functional Assessment of Anorexia\Cachexia Therapy ) with anorexia \ cachexia subscale .</measure>
    <time_frame>It will be assessed at week 8 of receiving the intervention.</time_frame>
    <description>Effect of mirtazapine in improving quality of life in patients with cachexia due to advanced cancer. This will be measured by an increase of 16 points in the FAACT which indicates ''improved'' quality of life. The FAACT questionnaire ( Functional Assessment of Anorexia\Cachexia Therapy ) with anorexia \ cachexia subscale is internally consistent , reliable and valid as a measure of health-related quality of life for persons with advanced cancer.&#xD;
We will contact their website to get the licence to use the questionnaire and to get its translated version.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in inflammatory cytokines associated with mirtazapine administration : quantitative c-reactive protein (CRP) , IL-6, and YKL-40 serum levels .</measure>
    <time_frame>It will be assessed at week 8 of receiving the intervention.</time_frame>
    <description>Changes in inflammatory cytokines associated with mirtazapine administration in patients with cachexia due to advanced cancer : quantitative c-reactive protein (CRP) and comparative analysis by enzyme-linked immunoassay (ELISA) will be performed on IL-6, and YKL-40 serum levels according to availability. They will be obtained at baseline (day 1 of treatment, immediately before first dose) and at week 8.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety of mirtazapine use : Toxicity will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0</measure>
    <time_frame>It will be assessed at baseline , then at 14-day intervals until day 28 and after 30 days from the date of the last dose of the study drug.</time_frame>
    <description>Safety of mirtazapine use in patients with cachexia due to advanced cancer.Toxicity will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. A traditional definition of dose-limiting toxicity (DLT) within the first cycle will be used (any grade 3 non-hematologic or grade 4 hematologic toxicity within 4 weeks and assessed as being at least possibly related to study drug).&#xD;
A toxicity questionnaire will be done at baseline and then at 14-day intervals until day 28.&#xD;
To fully assess the toxicity profile of the drug, the safety evaluation period in the trial will be extended 30 days from the date of the last dose of study drug.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">120</enrollment>
  <condition>Advanced Cancer</condition>
  <condition>Cancer Associated Anorexia - Cachexia</condition>
  <arm_group>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Mirtazapine 30 mg oral tablets ( Remeron 30 mg oral tablets ) , as half tablet daily , i.e , 15mg daily , before sleep for a duration of 8 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo oral tablets , as half tablet daily before sleep for a duration of 8 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mirtazapine 30 mg oral tablets</intervention_name>
    <description>Mirtazapine 30 mg oral tablets ( Remeron 30 mg oral tablets) , half tablet before sleep for 8 weeks</description>
    <arm_group_label>Arm A</arm_group_label>
    <other_name>Remeron 30 mg oral tablets</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo oral tablets</intervention_name>
    <description>Placebo oral tablets , half tablet daily before sleep for 8 weeks</description>
    <arm_group_label>Arm B</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with confirmed advanced cancer.&#xD;
&#xD;
          -  Patients with appetite score equal or more than 4 on a 0 to 10 scale (10 _ worst&#xD;
             appetite).&#xD;
&#xD;
          -  Patients with weight loss more than 5 % of body weight over 6 months . Or : Patients&#xD;
             with any degree of weight loss more than 2 % associated with BMI ( body mass index )&#xD;
             of less than 20.&#xD;
&#xD;
          -  Patients able to take pills orally and not dependent on tube feeding (no oral mucosal&#xD;
             inflammation interfering with oral intake or dysphagia as determined by clinical&#xD;
             examination).&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.&#xD;
&#xD;
          -  Normal organ function (creatinine ≤2× upper limit of normal, bilirubin ≤2; upper limit&#xD;
             of normal).&#xD;
&#xD;
          -  Ability to understand and willingness to sign written informed consent.&#xD;
&#xD;
          -  Patients could be receiving concurrent chemotherapy or radiation therapy.&#xD;
&#xD;
          -  Patients with an expected life span of at least 3 months.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with weight gain for known cause , e.g. , ascites.&#xD;
&#xD;
          -  Premenopausal women with childbearing potential with a positive pregnancy test.&#xD;
&#xD;
          -  Patients unable to maintain oral intake .&#xD;
&#xD;
          -  Patients with dementia or delirium.&#xD;
&#xD;
          -  Patients with uncontrolled symptoms that could impact appetite or caloric intake such&#xD;
             as nausea, pain, or depression will be excluded until their symptoms had stabilized&#xD;
             for at least 2 weeks.&#xD;
&#xD;
          -  Because improvement in anorexia and/or weight in depressed individuals could be due to&#xD;
             an antidepressant effect of mirtazapine, rather than to a direct effect on anorexia,&#xD;
             patients with moderate to severe depressive symptoms will be also excluded. the&#xD;
             screening instrument will be a single-item interview assessing depressed mood of the&#xD;
             Schedule for Affective Disorders and Schizophrenia (SADS) instrument which is&#xD;
             validated and highly accurate in screening for depression when compared to the gold&#xD;
             standard of semistructured diagnostic interviews, and is rated on a 6-point Likert&#xD;
             scale, where 0 = no depression and 6 = extreme feelings of depression. Patients with a&#xD;
             score of 4 or more will be excluded from the study as they are considered to be at&#xD;
             high risk for depression.&#xD;
&#xD;
          -  No treatment with antipsychotic agents such as risperidone, quetiapine, clozapine,&#xD;
             phenothiazine, or butyrophenone for 30 days prior to or during protocol therapy.&#xD;
&#xD;
          -  Patients with untreated vitamin B12 deficiency or endocrine abnormalities that could&#xD;
             affect appetite, such as thyroid dysfunction and hypoadrenalism.&#xD;
&#xD;
          -  Patients on supplements or medications with potential appetite-stimulating activity,&#xD;
             such as megestrol acetate, corticosteroids, or thalidomide, will be excluded unless&#xD;
             they are put on a stable dose for more than 2 weeks and continue to experience poor&#xD;
             appetite.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Catherine N Hunter, Ass. lecturer</last_name>
    <role>Principal Investigator</role>
    <affiliation>Clinical Oncology Department at Kasr Al Ainy NEMROCK</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Kasr Al Ainy - Cairo University - Faculty of Medicine</name>
      <address>
        <city>Cairo</city>
        <zip>11956</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>June 11, 2017</study_first_submitted>
  <study_first_submitted_qc>August 15, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 18, 2017</study_first_posted>
  <last_update_submitted>February 1, 2020</last_update_submitted>
  <last_update_submitted_qc>February 1, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 5, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Kasr El Aini Hospital</investigator_affiliation>
    <investigator_full_name>Catherine Naseef Hunter</investigator_full_name>
    <investigator_title>Assisstant Lecturer at clinical oncology department at Kasr Al Ainy NEMROCK</investigator_title>
  </responsible_party>
  <keyword>Mirtazapine</keyword>
  <keyword>Anorexia - Cachexia</keyword>
  <keyword>Advanced Cancer</keyword>
  <keyword>Appetite</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Wasting Syndrome</mesh_term>
    <mesh_term>Anorexia</mesh_term>
    <mesh_term>Cachexia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mirtazapine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>All data will be kept in records at clinical oncology department at Kasr Al Ainy NEMROCK to be available at anytime and shared with other researchers</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03254173
org study id: MCACS100
nct id: NCT03254173
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
A randomized controlled clinical trial will be conducted to assess the efficacy of the FDA
      approved drug , mirtazapine , in treatment of cancer associated anorexia cachexia syndrome.

      Two arms will be compared . Arm A will involve 50 patients with confirmed advanced cancer
      receiving mirtazapine 15 mg once daily for 8 weeks & Arm B will involve another 50 patients
      with confirmed advanced cancer receiving placebo for 8 weeks.

      Both arms will be compared to assess efficacy of mirtazapine in appetite stimulation
      primarily and to assess other outcomes secondarily which will be discussed later in details.
-  A Written consent is to be obtained from all patients before being enrolled in the
           study.

        -  Baseline Complete Blood Count , Liver function tests and kidney function tests will be
           obtained to assess safety to start the drug and to assess its dose adjustment.

        -  Two arms will be compared : mirtazapine oral 15mg daily versus placebo. This will be
           conducted on a double-blinded basis.

        -  Oral mirtazapine ( REMERON , RD , 30 mg tablets , Organon ) will be the original FDA
           approved drugs that will be used in the study.

        -  Treatment allocation will be concealed from patients, investigators, and study
           coordinators enrolling the participants.

        -  All patients will be counseled and given dietary advice by a dietician at baseline.

        -  Patients will be permitted to continue treatment at the same dose as scheduled as long
           as weight was stabilized (no loss greater than 10 % of body weight at baseline).

        -  Duration of therapy : Patients will remain on protocol for a duration of 8 weeks as long
           as they did not develop serious concurrent illness preventing further treatment,
           unacceptable adverse events (grade 3 or higher), the patient decides to withdraw from
           study, or the investigator judges that it is in the patient's best interest to
           discontinue treatment due to general or specific health conditions.

        -  Demographic data will include performance status, tumor type, sex, age, and percentage
           weight loss.

        -  The ESAS scale (Edmonton Symptom Assessment Scale ) will be used to assess the following
           10 symptoms experienced by patients with cancer during the previous 24 hours:

             1. pain.

             2. Fatigue.

             3. Nausea.

             4. Depression.

             5. Anxiety.

             6. Drowsiness.

             7. Dyspnea.

             8. Anorexia.

             9. Sleep disturbance.

            10. And feelings of well-being.

      The severity of each symptom is rated on a numerical scale of 0 to 10 (0_no symptom, 10_worst
      possible severity). The ESAS is both valid and reliable in the assessment of the intensity of
      symptoms in patients with cancer.

        -  The FAACT questionnaire ( Functional Assessment of Anorexia\Cachexia Therapy ) with
           anorexia \ cachexia subscale will be used to assess quality of life among the studied
           patients , in a form of questionnaire including :

             1. Physical well-being.

             2. Social well-being.

             3. Emotional well-being.

             4. Functional well-being.

             5. Additional concerns.

                The patient rates the answer on a scale of 0 to 4. The FACIT - Pal scale is
                internally consistent , reliable and valid as a measure of health-related quality
                of life for persons with advanced cancer.

                We will contact their website to get the licence to use the questionnaire and to
                get its translated version.

        -  Anthropometric measures to assess efficacy of mirtazapine in weight gain :

             1. Assessment of weight of the patient .

             2. Assessment of muscle strength ( via hand grip dynamometry , using the device named
                Lite 200 lb , Fabrication Enterprises Incorporated Company).

             3. Assessment of lean ( via bioimpedance analysis , using the device named BF100 ,
                Beurer Company ).

        -  Biological methods to assess efficacy of mirtazapine in modulating inflammatory cytokine
           media : quantitative c-reactive protein (CRP) and comparative analysis by enzyme-linked
           immunoassay (ELISA) will be performed on IL-6 ( Interleukin - 6 ) , and YKL-40 serum
           levels according to availability. They will be obtained at baseline (day 1 of treatment,
           immediately before first dose) and at week 8.

        -  Evaluation of safety and tolerability Patients who will receive at least one dose of
           study medication will be done.

        -  A traditional definition of dose-limiting toxicity (DLT) within the first cycle Will be
           used (any grade 3 non-hematologic or grade 4 hematologic toxicity within 4 weeks and
           assessed as being at least possibly related to study drug).

        -  A toxicity questionnaire will be done at baseline and then at 14-day intervals until day
           28.

      To fully assess the toxicity profile of the drug, the safety evaluation period in the trial
      will be extended 30 days from the date of the last dose of study drug.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: double-blinded randomized controlled trial.
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
masking description: Treatment allocation will be concealed from patients, investigators, and study coordinators enrolling the participants.
The pills used in the study ( either remeron or placebo ) will be kept into opaque containers , in order to be concealed from patients , investigators and study coordinators.
measure: Efficacy of mirtazapine in appetite stimulation in patients with cachexia due to advanced cancer with a change of increase of 1.5 degree on a numerical scale of 0 -10 as a target .
time frame: It will be assessed at week 4 of receiving the intervention. The 4-week duration of treatment is of sufficient length to obtain benefit from an effective intervention for appetite.
description: Efficacy of mirtazapine in appetite stimulation in patients with cachexia due to advanced cancer with a change of increase 1.5 degree on a scale of 0-10 as a target , where 0 represents minimum appetite and 10 represents maximum appetite.
measure: Efficacy of mirtazapine in weight gain. ''Improved'' weight will be defined as a gain of ≥ 1 kg and ''maintained weight'' will be defined as a loss of <500 g, or a gain of <1 kg.
time frame: It will be assessed at week 8 of receiving the intervention.
description: Efficacy of mirtazapine in weight gain in patients with cachexia due to advanced cancer.''Improved'' weight will be defined as a gain of ≥ 1 kg and ''maintained'' will be defined as a loss of <500 g, or a gain of <1 kg.
measure: Effect of mirtazapine in improving other symptoms , such as : nausea , vomiting , sleep with a change of decrease of ≥ 2 points on the ESAS ( Edmonton Symptom Assessment Scale ) from baseline.
time frame: It will be assessed at week 8 of receiving the intervention.
description: Effect of mirtazapine in improving other symptoms , such as : nausea , vomiting , sleep in patients with cachexia due to advanced cancer with a change of decrease of ≥ 2 points on the ESAS scale from baseline. The ESAS is both valid and reliable in the assessment of the intensity of symptoms in patients with cancer.
measure: Effect of mirtazapine in improving quality of life : will be measured by an increase of 16 points in the FAACT questionnaire ( Functional Assessment of Anorexia\Cachexia Therapy ) with anorexia \ cachexia subscale .
time frame: It will be assessed at week 8 of receiving the intervention.
description: Effect of mirtazapine in improving quality of life in patients with cachexia due to advanced cancer. This will be measured by an increase of 16 points in the FAACT which indicates ''improved'' quality of life. The FAACT questionnaire ( Functional Assessment of Anorexia\Cachexia Therapy ) with anorexia \ cachexia subscale is internally consistent , reliable and valid as a measure of health-related quality of life for persons with advanced cancer.
We will contact their website to get the licence to use the questionnaire and to get its translated version.
measure: Changes in inflammatory cytokines associated with mirtazapine administration : quantitative c-reactive protein (CRP) , IL-6, and YKL-40 serum levels .
time frame: It will be assessed at week 8 of receiving the intervention.
description: Changes in inflammatory cytokines associated with mirtazapine administration in patients with cachexia due to advanced cancer : quantitative c-reactive protein (CRP) and comparative analysis by enzyme-linked immunoassay (ELISA) will be performed on IL-6, and YKL-40 serum levels according to availability. They will be obtained at baseline (day 1 of treatment, immediately before first dose) and at week 8.
measure: Safety of mirtazapine use : Toxicity will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0
time frame: It will be assessed at baseline , then at 14-day intervals until day 28 and after 30 days from the date of the last dose of the study drug.
description: Safety of mirtazapine use in patients with cachexia due to advanced cancer.Toxicity will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. A traditional definition of dose-limiting toxicity (DLT) within the first cycle will be used (any grade 3 non-hematologic or grade 4 hematologic toxicity within 4 weeks and assessed as being at least possibly related to study drug).
A toxicity questionnaire will be done at baseline and then at 14-day intervals until day 28.
To fully assess the toxicity profile of the drug, the safety evaluation period in the trial will be extended 30 days from the date of the last dose of study drug.
arm group label: Arm A
arm group type: Active Comparator
description: Mirtazapine 30 mg oral tablets ( Remeron 30 mg oral tablets ) , as half tablet daily , i.e , 15mg daily , before sleep for a duration of 8 weeks
arm group label: Arm B
arm group type: Placebo Comparator
description: Placebo oral tablets , as half tablet daily before sleep for a duration of 8 weeks
intervention type: Drug
intervention name: Mirtazapine 30 mg oral tablets
description: Mirtazapine 30 mg oral tablets ( Remeron 30 mg oral tablets) , half tablet before sleep for 8 weeks
arm group label: Arm A
other name: Remeron 30 mg oral tablets
intervention type: Drug
intervention name: Placebo oral tablets
description: Placebo oral tablets , half tablet daily before sleep for 8 weeks
arm group label: Arm B
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Catherine N Hunter, Ass. lecturer
role: Principal Investigator
affiliation: Clinical Oncology Department at Kasr Al Ainy NEMROCK
facility: 
country: Egypt
responsible party type: Sponsor-Investigator
investigator affiliation: Kasr El Aini Hospital
investigator full name: Catherine Naseef Hunter
investigator title: Assisstant Lecturer at clinical oncology department at Kasr Al Ainy NEMROCK
mesh term: Wasting Syndrome
mesh term: Anorexia
mesh term: Cachexia
mesh term: Mirtazapine
sharing ipd: Yes
ipd description: All data will be kept in records at clinical oncology department at Kasr Al Ainy NEMROCK to be available at anytime and shared with other researchers