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.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 86
- 试验地点
- 1
- 主要终点
- Percentage of patients with Anorexia
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The Mirtazapine and placebo containers of same appearance will be identified with a code, which will be uncovered at the end of the study. The codes assigned to Mirtazapine and placebo will be protected by the protocols coordination of the Functional Unit of Thoracic Oncology. The code will be assigned to patients in order of admission, according to a list pre-established by random numbers without knowing to which group the attending physician, the nutritionist, the psychiatrist or the patient belongs.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Intervention group
arm to receive 15 to 30 mg of Mirtazapine for a period of 8 weeks.
干预措施: Mirtazapine (Drug)
Placebo group
arm to receive 15 to 30 mg of placebo for a period of 8 weeks.
干预措施: Placebo Oral Tablet (Drug)
结局指标
主要结局
Percentage of patients with Anorexia
时间窗: 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
时间窗: From the baseline assessment to 4 and 8 weeks
Total kilocalories consumed on average per day by a subject
次要结局
- Weight(From the baseline assessment to 8 weeks)
- Body Mass Index(From the baseline assessment to 8 weeks)
- Subjetive Global Assessment(From the baseline assessment to 8 weeks)
- Protein consumption(From the baseline assessment to 8 weeks)
- Lipids consumption(From the baseline assessment to 8 weeks)
- Carbohydrates consumption(From the baseline assessment to 8 weeks)
- Body fat(From the baseline assessment to 8 weeks)
- Fat free mass(From the baseline assessment to 8 weeks)
- phase angle(From the baseline assessment to 8 weeks)
- Quality of life - Global status(From the baseline assessment to 8 weeks)
- Quality of life - physical functioning(From the baseline assessment to 8 weeks)
- Quality of life - Emotional functioning(From the baseline assessment to 8 weeks)
- Quality of life - Social functioning(From the baseline assessment to 8 weeks)
- Quality of life -Role functioning(From the baseline assessment to 8 weeks)
- Quality of life - Cognitive functioning(From the baseline assessment to 8 weeks)
- Quality of life - Fatigue(From the baseline assessment to 8 weeks)
- Quality of life - loss of appetite(From the baseline assessment to 8 weeks)
- Quality of life - Nausea and vomiting(From the baseline assessment to 8 weeks)
- Depression(From the baseline assessment to 8 weeks)
- Anxiety(From the baseline assessment to 8 weeks)
研究者
Oscar Gerardo Arrieta Rodríguez
M.D.,M.Sc.
Instituto Nacional de Cancerologia de Mexico