Symptoms and General Pathology

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Thinness

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Mirtazapine

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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

Placebo oral tablets , as half tablet daily before sleep for a duration of 8 weeks

Mirtazapine 30 mg oral tablets ( Remeron 30 mg oral tablets) , half tablet before sleep for 8 weeks

Mirtazapine 30 mg oral tablets

Placebo oral tablets , half tablet daily before sleep for 8 weeks

Placebo oral tablets

Catherine N Hunter, Ass. lecturer

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.

double-blinded randomized controlled trial.

* 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.

Mirtazapine for Treatment of Cancer Associated Anorexia-cachexia

Mirtazapine for Treatment of Cancer Associated Anorexia-cachexia : a Randomized Controlled Clinical Trial

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

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.

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.

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.

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.

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.

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Mirtazapine for Treatment of Cancer Associated Anorexia-cachexia	NCT03254173	Advanced Cancer Cancer Associat...	Mirtazapine 30 ... Placebo oral ta...	18 Years -	Kasr El Aini Hospital
Mirtazapine for Treatment of Cancer Associated Anorexia-cachexia	NCT03254173	Advanced Cancer Cancer Associat...	Mirtazapine 30 ... Placebo oral ta...	18 Years -	Kasr El Aini Hospital

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