Effect of Mirtazapine Versus Placebo in Patients With Non-small Cell Lung Cancer and Anorexia

April 25, 2023 updated by: Oscar Gerardo Arrieta Rodríguez, Instituto Nacional de Cancerologia de Mexico

Effect of Mirtazapine Versus Placebo on Appetite, Nutritional Status and Quality of Life in Non-small Cell Lung cáncer Patients With Anorexia; Randomized Double-blind Clinical Trial.

The realization of this project will generate an important advance in knowledge regarding one of the most important comorbidities in cancer patients: malnutrition.

Currently, comprehensive treatments of cancer patients recognize the importance of the assessment of nutritional status, and the impact it has on the prognosis, quality of life and toxicity generated by cancer treatment. Due to this, it is imperative to offer diagnostic tools that identify patients in a timely manner and, in addition to this, offer therapeutic strategies for the improvement of nutritional status, in an adjuvant manner to their oncological treatment.

It is widely recognized that the cachexia-anorexia syndrome (CACS) is present in 30 to 80% of cases in cancer patients and this proportion increases as the disease progresses, with weight loss being a powerful predictor of shorter survival. Unfortunately, current therapies available to treat anorexia and / or cancer-associated cachexia offer only partial results, mainly because the intervention is late and the development of an earlier and more effective intervention is still sought. Mirtazapine has recently gained attention not only because of its antidepressant effect, but also because of its potential benefit in patients with anorexia and weight loss, recently reported in a phase II study. Therefore, it is important to continue its evaluation through a randomized, double-blind clinical trial in which the effect of mirtazapine is compared and it is determined if it is superior compared to placebo to increase appetite in patients with NSCLC who present with anorexia.

This type of strategy is a relevant therapeutic option in those patients in whom nutritional counseling by itself is not sufficient to counteract the damage caused by anorexia and to cope with or prevent the development of cachexia.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Lung cancer is the leading cause of cancer death in Mexico and the world. One of the comorbidities most commonly associated with this type of malignancy is malnutrition, which occurs in approximately 40-50% of newly diagnosed cases. In addition to its high incidence, malnutrition in patients with cancer is of great relevance due to the negative effect that this entails on the quality of life and the prognosis of patients, as well as the increase in toxicity associated with oncological treatment. Malnutrition is a pathological state in which the deficiency in the adequate contribution of energy contributes to its development, producing a systemic catabolic state; Its etiology is variable, however, in most patients malnutrition is associated with a lack of appetite, which is called anorexia.

Mirtazapine is a tetracyclic antidepressant which has been widely used for the treatment of depression. Several clinical studies have proven its efficacy in this indication, with more than 5000 patients endorsing its clinical effect compared to placebo, other tetracyclic antidepressants and trazodone. In addition to its effect on mood, it has been observed that mirtazapine, used in standard doses, induces weight gain, increasing appetite and food consumption compared to patients receiving placebo.

The increase in appetite with consequent weight gain and increased food intake may be due to the blocking of 5HT1b, 5-HT2, 5-HT3, H1 receptors, involved in the regulation of appetite. A pilot study of 2 doses of mirtazapine (15 or 30 mg per day) in ambulatory cancer patients with pain and other discomforts suggests that it provides a significant improvement in quality of life, particularly in weight and energy intake. Recently, another phase II study observed that 57% of oncology patients, ambulatory, non-depressed, increased their appetite and body weight when treated with mirtazapine for 4 weeks. Despite these encouraging data, the study included a small sample of patients, so it is not possible to generate robust conclusions from these data.

The objective of this protocol is to conduct a prospective, randomized, double-blind clinical trial to evaluate the effect of Mirtazapine on appetite, nutritional status and quality of life in patients with anorexia associated with lung cancer. The sample would include 86 patients, 43 patients with Mirtazapine and 43 sith placebo for 8 weeks, with an inducing dose of 15 mg to a máximum of 30 mg. The methodology for conducting this study consists of recruiting patients diagnosed with anorexia according to the anorexia-cachexia (ACS) scale, which has a cut-off point specifically validated for lung cáncer. Once the patient is selected, they are invited to participate in the study and an informed consent is requested. Subsequently a subjective global evaluation is performed, a 24-hour reminder of energy consumption, evaluation of anthropometric measures (weight, height,% weight loss, body mass index), evaluation of body composition (% fat, fat-free mass and phase angle), common gastrointestinal adverse effects of chemotherapy according to CTCAE, an evaluation of anxiety and depression (HADS) , as well as determination of quality of life through the questionnaire "The European organization for research and treatment of cancer quality of life questionnaire (QLQ) -C30 and (QLQ) LC-13", validated for Mexican population.

All determinations will be made at baseline, at 4 and at 8 weeks. All the variables are going to be evaluated inside each groups and between groups. It´s going to be considered significant p ≤ 0.05.

Study Type

Interventional

Enrollment (Actual)

86

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mexico
      • Mexico City, Mexico, 14080
        • Instituto Nacional de Cancerologia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Outpatients over 18 years of age who are receiving care in INCan with histopathological diagnosis of advanced stage non-small cell lung cancer (IIIB or IV).
  • A score ≤ 32 on the cachexia anorexia scale or ≥ 5% weight loss in the last month.
  • Good performance status (ECOG 0-2)
  • That they are receiving chemotherapy as standard treatment or tyrosine kinase inhibitors or immunotherapy.
  • Have a life expectancy> 8 weeks.
  • Accept and sign informed consent letter.

Exclusion Criteria:

  • Known allergy to mirtazapine
  • Patients who are treated with antidepressants
  • Patients who are under treatment with megestrol acetate
  • Patients with moderate hepatic and / or renal dysfunction (bilirubin level ≥ 1.5 x above normal limits (UNL), AST and ALT ≥ 5 x UNL, or creatinine ≥5 x UNL).
  • Those unable to take medication orally.
  • Patients with mechanical obstruction of the gastrointestinal tract, ascites or generalized edema.
  • Patients with a history of phenylketonuria (preparation contains phenylalanine).
  • Patients with delirium.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Intervention group
arm to receive 15 to 30 mg of Mirtazapine for a period of 8 weeks.
Drug: Mirtazapine
arm to receive 15 to 30 mg of Mirtazapine for a period of 8 weeks.
Placebo Comparator: Placebo group
arm to receive 15 to 30 mg of placebo for a period of 8 weeks.
Drug: Placebo Oral Tablet
arm to receive 15 to 30 mg of Placebo for a period of 8 weeks.
Other Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of patients with Anorexia
Time Frame: From the baseline assessment to 4 and 8 weeks

The primary endpoint will assess the percentage of patients who continue to present anorexia after 4 and 8 weeks of treatment with placebo or mirtazapine.

Anorexia will be defined as the lack of desire to eat, lack of appetite, as measured using the validated version of the Anorexia / Cachexia Scale from the Functional Assessment of Anorexia Cachexia Therapy (FAACT). A score of less than or equal to 24 will be considered diagnostic for anorexia.
From the baseline assessment to 4 and 8 weeks
Energy Consumption
Time Frame: From the baseline assessment to 4 and 8 weeks
Total kilocalories consumed on average per day by a subject
From the baseline assessment to 4 and 8 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Weight
Time Frame: From the baseline assessment to 8 weeks
Sum of all the components of the organism and represents the total body mass.
From the baseline assessment to 8 weeks
Body Mass Index
Time Frame: From the baseline assessment to 8 weeks
It is an index of the weight of a person in relation to his height BMI = Weight (Kg.) / [height (m) * height) (m)]
From the baseline assessment to 8 weeks
Subjetive Global Assessment
Time Frame: From the baseline assessment to 8 weeks

Practical, quick and lower cost method used to make a nutritional evaluation, which consists of 3 parts: Anamnesis, physical examination and qualification.

A: Patients with an adequate nutritional status B: Suspected malnutrition or moderate malnutrition C: Patients with severe malnutrition
From the baseline assessment to 8 weeks
Protein consumption
Time Frame: From the baseline assessment to 8 weeks
Grams of protein consumed on average per day by a subject
From the baseline assessment to 8 weeks
Lipids consumption
Time Frame: From the baseline assessment to 8 weeks
Grams of lipids consumed on average per day by a subject
From the baseline assessment to 8 weeks
Carbohydrates consumption
Time Frame: From the baseline assessment to 8 weeks
Grams of carbohydrates consumed on average per day by a subject
From the baseline assessment to 8 weeks
Body fat
Time Frame: From the baseline assessment to 8 weeks
Body fat
From the baseline assessment to 8 weeks
Fat free mass
Time Frame: From the baseline assessment to 8 weeks
skeletal muscle, visceral protein, plasma proteins, extracellular water, skin and skeleton.
From the baseline assessment to 8 weeks
phase angle
Time Frame: From the baseline assessment to 8 weeks
Angular transformation of the ratio of reactance to resistance
From the baseline assessment to 8 weeks
Quality of life - Global status
Time Frame: From the baseline assessment to 8 weeks

Physical, physiological and social factors in the life of a patient. The Global status of Quality of Life evaluation will be evaluated using the validated Mexican-Spanish version of the European Organization for the Research and Treatment of Cancer (EORTC) Quality of life questionnaires specific for cancer with the items 29 and 30 (QLQ-C30 version 3.0) and complemented with the quality of life questionnaire for lung cancer (QLQ-LC13).

Scores range from 0-100, with higher scores representing better quality of life.

The items included in each scale are calculated a raw count (average = s score) and the corresponding formula is applied to obtain the final count (Score).
From the baseline assessment to 8 weeks
Quality of life - physical functioning
Time Frame: From the baseline assessment to 8 weeks

The physical functioning will be evaluated using the validated Mexican-Spanish version of the European Organization for the Research and Treatment of Cancer (EORTC) Quality of life questionnaires specific for cancer using the physical functioning scale (from QLQ-C30 version 3.0).

Scores range from 0-100, with higher scores representing better physical functioning.

The items included in each scale are calculated a raw count (average = s score) and the corresponding formula is applied to obtain the final count (Score).
From the baseline assessment to 8 weeks
Quality of life -Role functioning
Time Frame: From the baseline assessment to 8 weeks

The role functioning will be evaluated using the validated Mexican-Spanish version of the European Organization for the Research and Treatment of Cancer (EORTC) Quality of life questionnaires specific for cancer using the role functioning scale (from QLQ-C30 version 3.0).

Scores range from 0-100, with higher scores representing better role functioning.

The items included in each scale are calculated a raw count (average = s score) and the corresponding formula is applied to obtain the final count (Score).
From the baseline assessment to 8 weeks
Quality of life - Emotional functioning
Time Frame: From the baseline assessment to 8 weeks

The emotional functioning will be evaluated using the validated Mexican-Spanish version of the European Organization for the Research and Treatment of Cancer (EORTC) Quality of life questionnaires specific for cancer using the emotional functioning scale (from QLQ-C30 version 3.0).

Scores range from 0-100, with higher scores representing better emotional functioning.

The items included in each scale are calculated a raw count (average = s score) and the corresponding formula is applied to obtain the final count (Score).
From the baseline assessment to 8 weeks
Quality of life - Cognitive functioning
Time Frame: From the baseline assessment to 8 weeks

The cognitive functioning will be evaluated using the validated Mexican-Spanish version of the European Organization for the Research and Treatment of Cancer (EORTC) Quality of life questionnaires specific for cancer using the cognitive functioning scale (from QLQ-C30 version 3.0).

Scores range from 0-100, with higher scores representing better cognitive functioning.

The items included in each scale are calculated a raw count (average = s score) and the corresponding formula is applied to obtain the final count (Score).
From the baseline assessment to 8 weeks
Quality of life - Social functioning
Time Frame: From the baseline assessment to 8 weeks

The social functioning will be evaluated using the validated Mexican-Spanish version of the European Organization for the Research and Treatment of Cancer (EORTC) Quality of life questionnaires specific for cancer using the social functioning scale (from QLQ-C30 version 3.0).

Scores range from 0-100, with higher scores representing better social functioning.

The items included in each scale are calculated a raw count (average = s score) and the corresponding formula is applied to obtain the final count (Score).
From the baseline assessment to 8 weeks
Quality of life - Fatigue
Time Frame: From the baseline assessment to 8 weeks

Fatigue will be evaluated using the validated Mexican-Spanish version of the European Organization for the Research and Treatment of Cancer (EORTC) Quality of life questionnaires specific for cancer using the fatigue symptom scale (from QLQ-C30 version 3.0).

Scores range from 0-100, with higher scores representing worse fatigue. The items included in each scale are calculated a raw count (average = s score) and the corresponding formula is applied to obtain the final count (Score).
From the baseline assessment to 8 weeks
Quality of life - Nausea and vomiting
Time Frame: From the baseline assessment to 8 weeks

Nausea and vomiting will be evaluated using the validated Mexican-Spanish version of the European Organization for the Research and Treatment of Cancer (EORTC) Quality of life questionnaires specific for cancer using the nausea and vomiting symptom scale (from QLQ-C30 version 3.0).

Scores range from 0-100, with higher scores representing worse nausea and vomiting.

The items included in each scale are calculated a raw count (average = s score) and the corresponding formula is applied to obtain the final count (Score).
From the baseline assessment to 8 weeks
Quality of life - loss of appetite
Time Frame: From the baseline assessment to 8 weeks

Loss of appetite will be evaluated using the validated Mexican-Spanish version of the European Organization for the Research and Treatment of Cancer (EORTC) Quality of life questionnaires specific for cancer using the loss of appetite single item (from QLQ-C30 version 3.0).

Scores range from 0-100, with higher scores representing worse loss of appetite.

The items included in each scale are calculated a raw count (average = s score) and the corresponding formula is applied to obtain the final count (Score).
From the baseline assessment to 8 weeks
Anxiety
Time Frame: From the baseline assessment to 8 weeks

Mental state characterized by great restlessness, intense excitement and extreme insecurity.

Anxiety will be evaluated using the Mexican version of the Hospital Anxiety and Depression Scale (HADS) which was validated by Galindo Vázquez et al. (2015) is comprised of a scale which includes 14 items, which have four options as answers (ranging from 0-3). Scores range from 0-21. Highest scores denote higher anxiety.
From the baseline assessment to 8 weeks
Depression
Time Frame: From the baseline assessment to 8 weeks
Illness or mental disorder that is characterized by a deep sadness, mood decay, low self-esteem, loss of interest in everything and decrease in psychic functions. Depression will be evaluated using the Mexican version of the Hospital Anxiety and Depression Scale (HADS) which was validated by Galindo Vázquez et al. (2015) is comprised of a scale which includes 14 items, which have four options as answers (ranging from 0-3). Scores range from 0-21. Highest scores denote higher depression.
From the baseline assessment to 8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Instituto Nacional de Cancerologia de Mexico

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 29, 2018

Primary Completion (Actual)

July 29, 2022

Study Completion (Actual)

October 29, 2022

Study Registration Dates

First Submitted

November 19, 2020

First Submitted That Met QC Criteria

February 8, 2021

First Posted (Actual)

February 10, 2021

Study Record Updates

Last Update Posted (Actual)

April 27, 2023

Last Update Submitted That Met QC Criteria

April 25, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Mirtazapine

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Anorexia

Clinical Trials on Mirtazapine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Finland

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe