AnorexiaNCT04748523
Effect of Mirtazapine Versus Placebo in Patients With Non-small Cell Lung Cancer and Anorexia
A study testing Mirtazapine in people with Anorexia and Non-small Cell Lung Cancer, run by Instituto Nacional de Cancerologia de Mexico at 1 site in Mexico.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anorexia, Non-small Cell Lung Cancer
- What is being tested?
- Mirtazapine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 86 participants
- Where
- 1 siteMexico
- Study dates
- 29 Aug 2018to 29 Oct 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read more
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.
Read the 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.
- Conditions
- Anorexia, Non-small Cell Lung Cancer
- Being tested
- Mirtazapine, Placebo Oral Tablet
- Medical subject headings
- Anorexia, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MirtazapineDrug
arm to receive 15 to 30 mg of Mirtazapine for a period of 8 weeks.
Placebo Oral TabletDrug
Also called Placebo
arm to receive 15 to 30 mg of Placebo for a period of 8 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Intervention group | Active comparator | arm to receive 15 to 30 mg of Mirtazapine for a period of 8 weeks. Receives: Drug: Mirtazapine |
| Placebo group | Placebo comparator | arm to receive 15 to 30 mg of placebo for a period of 8 weeks. Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of patients with Anorexia
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.
Measured: From the baseline assessment to 4 and 8 weeks
Energy Consumption
Total kilocalories consumed on average per day by a subject
Measured: From the baseline assessment to 4 and 8 weeks
Secondary outcomes (20)
Weight
Sum of all the components of the organism and represents the total body mass.
Measured: From the baseline assessment to 8 weeks
Body Mass Index
It is an index of the weight of a person in relation to his height BMI = Weight (Kg.) / [height (m) * height) (m)]
Measured: From the baseline assessment to 8 weeks
Subjetive Global Assessment
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
Measured: From the baseline assessment to 8 weeks
Protein consumption
Grams of protein consumed on average per day by a subject
Measured: From the baseline assessment to 8 weeks
Lipids consumption
Grams of lipids consumed on average per day by a subject
Measured: From the baseline assessment to 8 weeks
Carbohydrates consumption
Grams of carbohydrates consumed on average per day by a subject
Measured: From the baseline assessment to 8 weeks
Body fat
Body fat
Measured: From the baseline assessment to 8 weeks
Fat free mass
skeletal muscle, visceral protein, plasma proteins, extracellular water, skin and skeleton.
Measured: From the baseline assessment to 8 weeks
phase angle
Angular transformation of the ratio of reactance to resistance
Measured: From the baseline assessment to 8 weeks
Quality of life - Global status
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).
Measured: From the baseline assessment to 8 weeks
Quality of life - physical functioning
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).
Measured: From the baseline assessment to 8 weeks
Quality of life -Role functioning
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).
Measured: From the baseline assessment to 8 weeks
Quality of life - Emotional functioning
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).
Measured: From the baseline assessment to 8 weeks
Quality of life - Cognitive functioning
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).
Measured: From the baseline assessment to 8 weeks
Quality of life - Social functioning
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).
Measured: From the baseline assessment to 8 weeks
Quality of life - Fatigue
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).
Measured: From the baseline assessment to 8 weeks
Quality of life - Nausea and vomiting
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).
Measured: From the baseline assessment to 8 weeks
Quality of life - loss of appetite
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).
Measured: From the baseline assessment to 8 weeks
Anxiety
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.
Measured: From the baseline assessment to 8 weeks
Depression
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.
Measured: From the baseline assessment to 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2021
- Study start29 Aug 2018
- Primary completion29 Jul 2022
- Study completion29 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (25)Papers the sponsor has linked to this study.
- Other trials for AnorexiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, double-blind clinical trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 86 participants (actual)
Sponsor and investigators
- Lead sponsor
- Instituto Nacional de Cancerologia de Mexico
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Oscar Gerardo Arrieta Rodríguez, Instituto Nacional de Cancerologia de Mexico
- Investigators
- Oscar G Arrieta Rodriguez, M.D., M.Sc., Principal investigator, Instituto Nacional de Cancerología de México
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04748523
- Sponsor's protocol ID
- Mirtazapine
- Status last verified
- Apr 2023
- First submitted
- 19 Nov 2020
- Last updated
- 27 Apr 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015 Mar 1;136(5):E359-86. doi: 10.1002/ijc.29210. Epub 2014 Oct 9.
PubMed 25220842Watanabe H, Yamamoto N, Tamura T, Shimoyama T, Hotta K, Inoue A, Sawada M, Akiyama Y, Kusaba H, Nokihara H, Sekine I, Kunitoh H, Ohe Y, Kodama T, Saijo N. Study of paclitaxel and dose escalation of cisplatin in patients with advanced non-small cell lung cancer. Jpn J Clin Oncol. 2003 Dec;33(12):626-30. doi: 10.1093/jjco/hyg116.
PubMed 14769840Sarhill N, Mahmoud FA, Christie R, Tahir A. Assessment of nutritional status and fluid deficits in advanced cancer. Am J Hosp Palliat Care. 2003 Nov-Dec;20(6):465-73. doi: 10.1177/104990910302000610.
PubMed 14649565Arrieta O, Michel Ortega RM, Villanueva-Rodriguez G, Serna-Thome MG, Flores-Estrada D, Diaz-Romero C, Rodriguez CM, Martinez L, Sanchez-Lara K. Association of nutritional status and serum albumin levels with development of toxicity in patients with advanced non-small cell lung cancer treated with paclitaxel-cisplatin chemotherapy: a prospective study. BMC Cancer. 2010 Feb 21;10:50. doi: 10.1186/1471-2407-10-50.
PubMed 20170547Sanchez-Lara K, Turcott JG, Juarez E, Guevara P, Nunez-Valencia C, Onate-Ocana LF, Flores D, Arrieta O. Association of nutrition parameters including bioelectrical impedance and systemic inflammatory response with quality of life and prognosis in patients with advanced non-small-cell lung cancer: a prospective study. Nutr Cancer. 2012;64(4):526-34. doi: 10.1080/01635581.2012.668744. Epub 2012 Apr 10.
PubMed 22489794Wie GA, Cho YA, Kim SY, Kim SM, Bae JM, Joung H. Prevalence and risk factors of malnutrition among cancer patients according to tumor location and stage in the National Cancer Center in Korea. Nutrition. 2010 Mar;26(3):263-8. doi: 10.1016/j.nut.2009.04.013. Epub 2009 Aug 8.
PubMed 19665873Ross PJ, Ashley S, Norton A, Priest K, Waters JS, Eisen T, Smith IE, O'Brien ME. Do patients with weight loss have a worse outcome when undergoing chemotherapy for lung cancers? Br J Cancer. 2004 May 17;90(10):1905-11. doi: 10.1038/sj.bjc.6601781.
PubMed 15138470Slaviero KA, Read JA, Clarke SJ, Rivory LP. Baseline nutritional assessment in advanced cancer patients receiving palliative chemotherapy. Nutr Cancer. 2003;46(2):148-57. doi: 10.1207/S15327914NC4602_07.
PubMed 14690790Muscaritoli M, Anker SD, Argiles J, Aversa Z, Bauer JM, Biolo G, Boirie Y, Bosaeus I, Cederholm T, Costelli P, Fearon KC, Laviano A, Maggio M, Rossi Fanelli F, Schneider SM, Schols A, Sieber CC. Consensus definition of sarcopenia, cachexia and pre-cachexia: joint document elaborated by Special Interest Groups (SIG) "cachexia-anorexia in chronic wasting diseases" and "nutrition in geriatrics". Clin Nutr. 2010 Apr;29(2):154-9. doi: 10.1016/j.clnu.2009.12.004. Epub 2010 Jan 8.
PubMed 20060626Marin Caro MM, Laviano A, Pichard C. Impact of nutrition on quality of life during cancer. Curr Opin Clin Nutr Metab Care. 2007 Jul;10(4):480-7. doi: 10.1097/MCO.0b013e3281e2c983.
PubMed 17563467Kosacka M, Werynska B, Golecki M, Jankowska R, Passowicz-Muszynska E. [The incidence and pathogenesis of cancer anorexia-cachexia syndrome in lung cancer]. Pneumonol Alergol Pol. 2008;76(5):360-5. Polish.
PubMed 19003767Laviano A, Meguid MM, Inui A, Muscaritoli M, Rossi-Fanelli F. Therapy insight: Cancer anorexia-cachexia syndrome--when all you can eat is yourself. Nat Clin Pract Oncol. 2005 Mar;2(3):158-65. doi: 10.1038/ncponc0112.
PubMed 16264909Dewys WD, Begg C, Lavin PT, Band PR, Bennett JM, Bertino JR, Cohen MH, Douglass HO Jr, Engstrom PF, Ezdinli EZ, Horton J, Johnson GJ, Moertel CG, Oken MM, Perlia C, Rosenbaum C, Silverstein MN, Skeel RT, Sponzo RW, Tormey DC. Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. Am J Med. 1980 Oct;69(4):491-7. doi: 10.1016/s0149-2918(05)80001-3.
PubMed 7424938Martin L, Senesse P, Gioulbasanis I, Antoun S, Bozzetti F, Deans C, Strasser F, Thoresen L, Jagoe RT, Chasen M, Lundholm K, Bosaeus I, Fearon KH, Baracos VE. Diagnostic criteria for the classification of cancer-associated weight loss. J Clin Oncol. 2015 Jan 1;33(1):90-9. doi: 10.1200/JCO.2014.56.1894. Epub 2014 Nov 24.
PubMed 25422490LeBlanc TW, Samsa GP, Wolf SP, Locke SC, Cella DF, Abernethy AP. Validation and real-world assessment of the Functional Assessment of Anorexia-Cachexia Therapy (FAACT) scale in patients with advanced non-small cell lung cancer and the cancer anorexia-cachexia syndrome (CACS). Support Care Cancer. 2015 Aug;23(8):2341-7. doi: 10.1007/s00520-015-2606-z. Epub 2015 Jan 14.
PubMed 25586527
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT04748523
- Acronym / sponsor ID
- Mirtazapine
- Conditions
- Anorexia, Non-small Cell Lung Cancer
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 86 participants (actual)
- Lead sponsor
- Instituto Nacional de Cancerologia de MexicoUniversity, hospital or other
- Study start
- 29 Aug 2018 (actual)
- Primary completion
- 29 Jul 2022 (actual)
- Study completion
- 29 Oct 2022 (actual)
- First posted
- 10 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, double-blind clinical trial
| Arm | Type | Receives |
|---|---|---|
| Intervention group | Active comparator | Drug: Mirtazapinearm to receive 15 to 30 mg of Mirtazapine for a period of 8 weeks. |
| Placebo group | Placebo comparator | Drug: Placebo Oral Tabletarm to receive 15 to 30 mg of placebo for a period of 8 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mirtazapinearm to receive 15 to 30 mg of Mirtazapine for a period of 8 weeks. | Drug | Intervention group |
| Placebo Oral TabletAlso: Placeboarm to receive 15 to 30 mg of Placebo for a period of 8 weeks. | Drug | Placebo group |
Primary outcome
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.
Energy Consumption
Time frame: From the baseline assessment to 4 and 8 weeks
Total kilocalories consumed on average per day by a subject
20 secondary outcomes
Weight
Time frame: From the baseline assessment to 8 weeks
Body Mass Index
Time frame: From the baseline assessment to 8 weeks
Subjetive Global Assessment
Time frame: From the baseline assessment to 8 weeks
Protein consumption
Time frame: From the baseline assessment to 8 weeks
Lipids consumption
Time frame: From the baseline assessment to 8 weeks
Carbohydrates consumption
Time frame: From the baseline assessment to 8 weeks
Body fat
Time frame: From the baseline assessment to 8 weeks
Fat free mass
Time frame: From the baseline assessment to 8 weeks
phase angle
Time frame: From the baseline assessment to 8 weeks
Quality of life - Global status
Time frame: From the baseline assessment to 8 weeks
Quality of life - physical functioning
Time frame: From the baseline assessment to 8 weeks
Quality of life -Role functioning
Time frame: From the baseline assessment to 8 weeks
Quality of life - Emotional functioning
Time frame: From the baseline assessment to 8 weeks
Quality of life - Cognitive functioning
Time frame: From the baseline assessment to 8 weeks
Quality of life - Social functioning
Time frame: From the baseline assessment to 8 weeks
Quality of life - Fatigue
Time frame: From the baseline assessment to 8 weeks
Quality of life - Nausea and vomiting
Time frame: From the baseline assessment to 8 weeks
Quality of life - loss of appetite
Time frame: From the baseline assessment to 8 weeks
Anxiety
Time frame: From the baseline assessment to 8 weeks
Depression
Time frame: From the baseline assessment to 8 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2023.
- Background: PubMed 25220842Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015 Mar 1;136(5):E359-86. doi: 10.1002/ijc.29210. Epub 2014 Oct 9.
- Background: PubMed 14769840Watanabe H, Yamamoto N, Tamura T, Shimoyama T, Hotta K, Inoue A, Sawada M, Akiyama Y, Kusaba H, Nokihara H, Sekine I, Kunitoh H, Ohe Y, Kodama T, Saijo N. Study of paclitaxel and dose escalation of cisplatin in patients with advanced non-small cell lung cancer. Jpn J Clin Oncol. 2003 Dec;33(12):626-30. doi: 10.1093/jjco/hyg116.
- Background: PubMed 14649565Sarhill N, Mahmoud FA, Christie R, Tahir A. Assessment of nutritional status and fluid deficits in advanced cancer. Am J Hosp Palliat Care. 2003 Nov-Dec;20(6):465-73. doi: 10.1177/104990910302000610.
- Background: PubMed 20170547Arrieta O, Michel Ortega RM, Villanueva-Rodriguez G, Serna-Thome MG, Flores-Estrada D, Diaz-Romero C, Rodriguez CM, Martinez L, Sanchez-Lara K. Association of nutritional status and serum albumin levels with development of toxicity in patients with advanced non-small cell lung cancer treated with paclitaxel-cisplatin chemotherapy: a prospective study. BMC Cancer. 2010 Feb 21;10:50. doi: 10.1186/1471-2407-10-50.
- Background: PubMed 22489794Sanchez-Lara K, Turcott JG, Juarez E, Guevara P, Nunez-Valencia C, Onate-Ocana LF, Flores D, Arrieta O. Association of nutrition parameters including bioelectrical impedance and systemic inflammatory response with quality of life and prognosis in patients with advanced non-small-cell lung cancer: a prospective study. Nutr Cancer. 2012;64(4):526-34. doi: 10.1080/01635581.2012.668744. Epub 2012 Apr 10.
- Background: PubMed 19665873Wie GA, Cho YA, Kim SY, Kim SM, Bae JM, Joung H. Prevalence and risk factors of malnutrition among cancer patients according to tumor location and stage in the National Cancer Center in Korea. Nutrition. 2010 Mar;26(3):263-8. doi: 10.1016/j.nut.2009.04.013. Epub 2009 Aug 8.
- Background: PubMed 15138470Ross PJ, Ashley S, Norton A, Priest K, Waters JS, Eisen T, Smith IE, O'Brien ME. Do patients with weight loss have a worse outcome when undergoing chemotherapy for lung cancers? Br J Cancer. 2004 May 17;90(10):1905-11. doi: 10.1038/sj.bjc.6601781.
- Background: PubMed 14690790Slaviero KA, Read JA, Clarke SJ, Rivory LP. Baseline nutritional assessment in advanced cancer patients receiving palliative chemotherapy. Nutr Cancer. 2003;46(2):148-57. doi: 10.1207/S15327914NC4602_07.
- Background: PubMed 20060626Muscaritoli M, Anker SD, Argiles J, Aversa Z, Bauer JM, Biolo G, Boirie Y, Bosaeus I, Cederholm T, Costelli P, Fearon KC, Laviano A, Maggio M, Rossi Fanelli F, Schneider SM, Schols A, Sieber CC. Consensus definition of sarcopenia, cachexia and pre-cachexia: joint document elaborated by Special Interest Groups (SIG) "cachexia-anorexia in chronic wasting diseases" and "nutrition in geriatrics". Clin Nutr. 2010 Apr;29(2):154-9. doi: 10.1016/j.clnu.2009.12.004. Epub 2010 Jan 8.
- Background: PubMed 17563467Marin Caro MM, Laviano A, Pichard C. Impact of nutrition on quality of life during cancer. Curr Opin Clin Nutr Metab Care. 2007 Jul;10(4):480-7. doi: 10.1097/MCO.0b013e3281e2c983.
- Background: PubMed 19003767Kosacka M, Werynska B, Golecki M, Jankowska R, Passowicz-Muszynska E. [The incidence and pathogenesis of cancer anorexia-cachexia syndrome in lung cancer]. Pneumonol Alergol Pol. 2008;76(5):360-5. Polish.
- Background: PubMed 16264909Laviano A, Meguid MM, Inui A, Muscaritoli M, Rossi-Fanelli F. Therapy insight: Cancer anorexia-cachexia syndrome--when all you can eat is yourself. Nat Clin Pract Oncol. 2005 Mar;2(3):158-65. doi: 10.1038/ncponc0112.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Oscar G Arrieta Rodriguez, M.D., M.Sc. principal investigator
Instituto Nacional de Cancerología de México
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Mirtazapine in people with Anorexia and Non-small Cell Lung Cancer, run by Instituto Nacional de Cancerologia de Mexico at 1 site in Mexico.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of patients with Anorexia (time frame: From the baseline assessment to 4 and 8 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04748523, which also lists 25 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2023.