Fufang E'Jiao Jiang Intervening Cancer-related Fatigue

Study Overview
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Brief Summary
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With the therapeutic tool of carcinoma increasing, life span extending, the solicitude for the patients'quality of life appear more important. Cancer-related fatigue (CRF) is one of the most prevalent and debilitating symptoms experienced by people with cancer. It can persist for months or years after cancer therapy is completed and has a negative impact on all areas of function. Meaningful evidence-based treatment options for CRF are extremely limited and finding safe, inexpensive, and effective interventions for managing this distressing symptom are urgently needed. Our previous clinical experience have shown that traditional Chinese medicine（TCM） had a great effect on improving CRF, Several studies proven that its'mechanism were related to the regulation of immune function and endocrine hormones. Fufang E'Jiao Jiang (FFEJJICRF) is a commonly-used Chinese patent medicine and successfully marketed in China for many years, which are effective in improvement for TCM symptoms of deficiency with qi and blood. This proposal will investigate the effects of FFEJJICRF on CRF among non-small cell lung cancer, colorectal cancer, and gastric cancer, so as to find a new way for curing it in clinical.

Detailed Description
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By conducting large sample, multicenter, double-blind, randomized comparison clinical research, this test will investigate the effects of fufang E'Jiao Jiang intervening cancer-related fatigue (CRF) with deficiency of qi and blood, under the guidance of its specification. This test choose the improvement of fatigue degree as key indicator, and choose the improvement both symptoms of patients and quality of life as second indicators. And last, the study will try to verify its safety and efficacy with some haematological indexs and reveal its mechanism from the perspectives of hormone, immune and metabonomics, so as to explore the advantages of traditional Chinese medicine（TCM） in the treatment of CRF and support some high quality, internationally recognized clinical evidence.

Official Title
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The Study on the Clinical Value of Fufang E'Jiao Jiang Intervening Cancer-related Fatigue (Deficiency of Qi and Blood)

Conditions
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Cancer-related Fatigue

Intervention / Treatment
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* Drug: Fufang E'Jiao Jiang
* Drug: placebo containing low-dose fufang E'Jiao Jiang


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The age of patients between 18 and 75，gender not limited. Patients that pathologically diagnosed with colorectal cancer, non-small cell lung cancer (NSCLC) or gastric cancer. The patients' TNM stage of NSCLC is IIIB-IV, colorectal cancer is IV, and gastric cancer is IV, in addition all of them should be with tumors that can not be radically resected. If patients have not received chemotherapy, they should be evaluated that tumor will not progress within 30 days, and their bodies can tolerate intravenous targeted therapy. Patients who meet the diagnostic criterion for cancer related fatigue with deficiency of qi and blood. The expected survival period is more than 3 months. Fatigue score evaluated by visual analogue fatigue scale isn't lower than 4, and Karnofsky scale score isn't lower than 60. Good compliance and agreeable to sign an informed consent before test. Subjects agree not to participate in other intervention studies during test. Exclusion Criteria: Those who need immunotherapy or radiotherapy during the test. Those who have significant trauma injuries in the past one month. Those who have severe bleeding or systemic infection diseases that had not been completely controlled. Those who have tangible proofs of marrow or central nervous system metastasis. Those who have received erythropoietin or blood transfusion within 1 month before test. Those who have hypersplenism, hyperthyroidism, desmosis, tuberculosis and other diseases that have not been completely controlled. Those who complicated with serious diseases such as cardiovascular or cerebrovascular system diseases, active hepatitis, disfunction of liver or kidney. Those who are known or suspected to be allergic to test drugs. Those who have eaten EJiao products in the past 2 weeks. Those who have occurred Ileus. Those suffering from severe malabsorption or other diseases that affect gastrointestinal absorption. Those who cannot understand, read and fill in the self-rating scale due to their level of knowledge or intelligence. Those who may happen any unstable conditions or conditions that endanger the patient's safety or compliance, for example the spirits. Those who have been diagnosed with other malignant tumors (except fully treated cervix and skin carcinoma in situ, or other tumors that have been surgically cured and not recurred for at least 5 years) . Those who participated in other therapeutic clinical trials within 30 days. Pregnant or nursing women, or childbearing female that are inadequate contraception. Those who are inappropriate to participate in the study determined by investigators.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group<br>Fufang E'Jiao Jiang, 20milliliters(mL) once, 3 times a day, continuous intervention for 21days each cycle, and use 2 cycles | Drug: Fufang E'Jiao Jiang<br>* Fufang E'Jiao Jiang, 20milliliters(mL) once, 3 times a day, continuous intervention for 21 days each cycle, and use 2 cycles<br>* Other names: A listed Chinese Medicine;|
| Placebo Comparator: control group<br>Placebo containing low-dose Fufang E'Jiao Jiang, 20mL once, 3 times a day, continuous intervention for 21 days each cycle, and use 2 cycles | Drug: placebo containing low-dose fufang E'Jiao Jiang<br>* placebo containing low-dose Fufang E'Jiao Jiang, 20mL once, 3 times a day, continuous intervention for 21 days each cycle, and use 2 cycles<br>* Other names: placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fatigue degree with the Piper fatigue scale (Piper) | Piper is composed of 24 questions assessing total CRF, as well as subscales of behavioral, affective, sensory, and cognitive/mood fatigue. Each question is cored from 0 to10 points, where a higher score indicates severe symptoms; 1 to 3 point is mild, 4 to 6 point is moderate, and 7 to 10 point is severe. Piper is taken at the baseline, 1 weeks, 3 weeks,4 weeks, and 6 weeks after treatment | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The occurrence of myelosuppression during chemotherapy | 1)the duration time of myelosuppression; 2) the proportion among them that should be intervened with salvage treatments; the salvage treatments, including their variety, quantity and duration times; 3) the incidence and duration time of grade 3-4 myelosuppression. Those measurements were recorded and calculated separately at the end of the study. | 10 weeks | 
| The amounts of leukocyte cells, hemoglobin and platelet in peripheral blood | Those who are receiving chemotherapy should be measured at the baseline, 1 weeks, 3 weeks,4 weeks, 6 weeks and 10 weeks after treatment. Those who are not receiving chemotherapy should be measured at the baseline, 3 weeks, 6 weeks, 10 weeks. | 10 weeks | 
| Change of patients' living quality with the Edmonton symptom assessment scale(ESAS) | Changes of patients' living quality with ESAS to measure participants'responses to 11 common symptoms (pain, fatigue, nausea, depression, anxiety, drowsiness, shortness of breath, appetite, sleep problems, feeling of well-being and pruritus). Intensity of symptoms rated on a 0 to 10 scale from 0 no symptom to 10 worst possible symptom | 10 weeks | 
| Change of patients' functional status with Karnofsky performance status (KPS) | KPS Scores ranged from 100 to 0,The higher score represent the better health, the more likely that you are able to tolerate the side effects of treatment. It is generally considered that Karnofsky80 score or above represent patients can live independently, 60 80 score represent semi-independently, Under 60 represent patients often need help in living. | 10 weeks | 
| Quality of Life with Functional assessment of cancer therapy-fatigue（FACT-F） | FACT-F investigates participants from six dimensions (physiology, social/family status, emotion, function, fatigue, tumor) and each question is rated on a 5-point Likert scale. Higher scores represent more agreeable with the content of the items | 6 weeks | 
| Aldosterone, insulin-like growth factor, cortisol, growth hormone | Levels of serum hormone on aldosterone, insulin-like growth factor, cortisol, growth hormone | 6 weeks | 
| Change from baseline in lymphocyte subsets counts up to 6 Weeks: T Cell, B Cell, Natural Killer Cell (T,B,NK) | Lymphocyte subsets include T cell, B cell and Natural killer (NK) cells | 6 weeks | 
| Change from baseline in T-cells Subsets Counts up to 6 Weeks: T-Cells Subsets | T-cells Subsets Counts up to 6 Weeks: T-Cells Subsets | 6 weeks | 
| T-Cell Cytokines | T-cell cytokine subsets include IFNγ, IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-17A,IL-17F,IL-22,TNFα,TNFβ | 6 weeks | 
| Circulating metabolite concentrations by nontargeted metabolomics techniques | Blood concentrations of metabolites including amino acids, acylcarnitines, hexoses, biogenic amines, phosphatidylcholines, and sphingomyelins | 6 weeks | 
| Triiodothyronine, free triiodothyronine, bound thyroxine, free thyroxine, thyroid stimulating hormone | Thyroid hormones index | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Traditional Chinese medicine, Fufang E'Jiao Jiang, Randomized controlled trial