Trial Title:
Cangpo Liujun Prescription on Cancer-related Fatigue in Advanced Colorectal Cancer With Spleen Deficiency and Dampness Excess
NCT ID:
NCT06394128
Condition:
Cancer-Related Fatigue
Colorectal Cancer
Conditions: Official terms:
Colorectal Neoplasms
Fatigue
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
Single (Participant)
Intervention:
Intervention type:
Drug
Intervention name:
Cangpo Liujun Prescription
Description:
Based on the diagnostic criteria of spleen deficiency and dampness excess syndrome,
Cangpo Liujun Prescription could be used to treat cancer-related fatigue in patients with
advanced colorectal cancer undergoing second-line chemotherapy.
Arm group label:
Cangpo Liujun Prescription
Arm group label:
Placebo
Other name:
CPLJ
Summary:
The goal of this clinical trial is to learn if Cangpo Liujun Prescription works to treat
cancer-related fatigue in patients with advanced colorectal cancer undergoing second-line
chemotherapy with spleen deficiency and dampness excess. It will also learn about the
safety of Cangpo Liujun Prescription. The main questions it aims to answer are:
Does Cangpo Liujun Prescription improve the fatigue symptoms for participants? How about
the relationship between taking Cangpo Liujun Prescription and distribution of intestinal
flora?
Researchers will compare Cangpo Liujun Prescription to a placebo (a look-alike substance
that contains no drug) to see if Cangpo Liujun decoction works to treat cancer-related
fatigue in patients with advanced colorectal cancer undergoing second-line chemotherapy
with spleen deficiency and dampness excess.
Participants will:
Take Cangpo Liujun Prescription or a placebo every day for 3 months Visit the clinic once
every 2 weeks for checkups and tests Keep a diary of their symptoms Take blood samples to
detect immune function and inflammatory factors Collected Feces for gut microbiota
analysis
Detailed description:
1. Patients with advanced colorectal cancer undergoing chemotherapy constitute a
significant demographic affected by cancer-related fatigue (CRF).
CRF, as delineated by NCCN guidelines, is described as enduring, subjective
physical, emotional, and/or cognitive weariness or fatigue related to cancer or its
treatment, significantly interfering with daily life and function. It stands as one
of the most common and severe accompanying symptoms among cancer patients, with
durations extending up to five years for a quarter to a third of patients. The
etiology of CRF is complex, with factors including tumor-related factors,
treatment-related factors (surgery, radiotherapy, chemotherapy, immunotherapy,
etc.), comorbidities (anemia, thyroid dysfunction, etc.), and psychosocial factors
(anxiety, depression, etc.). CRF exerts various adverse effects on patients,
significantly diminishing their quality of life, including changes in daily habits,
decreased vitality, a sense of loss of control, social isolation, and exacerbation
of other accompanying symptoms. Moreover, CRF may reduce patients' completion rates
of anti-tumor treatment, consequently diminishing their survival periods,
highlighting its substantial detrimental impact. Studies indicate that approximately
33% of colorectal cancer patients experience CRF after chemotherapy, with the
incidence rising to two-thirds in advanced colorectal cancer patients, likely
associated with multiple chemotherapy treatments and low nutritional status.
Chemotherapy can lead to immunosuppression, tissue cell damage, and release of
inflammatory cytokines. Among these, cytokines play a crucial role in CRF formation,
inducing central fatigue through mechanisms such as anemia, cachexia, and disruption
of the hypothalamic-pituitary-adrenal axis. Additionally, regimens such as
oxaliplatin and its combinations (FOLFOX, FOLFIRI, FOLFOXIRI) used in colorectal
cancer treatment can cause mitochondrial and energy homeostasis dysregulation,
leading to skeletal muscle fatigue, with cumulative toxicity. Reduced energy intake
due to chemotherapy often results in prolonged low nutritional status in colorectal
cancer patients. Decreased synthesis of proteinaceous substances and accumulation of
certain metabolites alter ATP metabolism within muscle cells, thereby precipitating
peripheral fatigue.
2. The principal pathogenesis of cancer-related fatigue (CRF) in patients undergoing
second-line treatment for colorectal cancer is spleen deficiency and dampness
accumulation.
Although ancient Chinese medical texts do not directly mention "colorectal cancer"
or "tumors," traditional Chinese medicine has a deep-rooted understanding of similar
symptoms associated with clinical manifestations, such as "intestinal tumors" and
"accumulations," found in the "Inner Canon." The "Surgical Orthodoxies · Doctrine of
Internal Infections" elucidates that spleen deficiency leads to the accumulation of
damp toxins, which, over time, accumulate heat. This accumulation of damp-heat
toxins flows into the intestines, resulting in poor local circulation of qi and
blood and the coagulation of damp toxins into cancerous masses. Prolonged retention
of tumors in the intestines depletes qi and injures body fluids, exacerbated by
chemotherapy and targeted therapies, giving rise to a clinical presentation akin to
traditional Chinese medicine's concept of "deficiency fatigue." This includes a
series of symptoms such as visceral function decline, overall debilitation,
weakness, lethargy, emaciation, and increased inclination toward sleep, aligning
closely with the scope of CRF. The term "deficiency fatigue" was first documented by
Zhang Zhongjing in "Synopsis of the Golden Chamber · Blood Stasis Deficiency Fatigue
Disease Pulse Syndrome and Treatment," illustrating that spleen deficiency is the
primary pathogenesis of deficiency fatigue and CRF. According to traditional Chinese
medicine, CRF is predominantly characterized by deficiency patterns, often
compounded with mixed patterns of deficiency and excess, with the affected organs
primarily involving the spleen, lungs, liver, and kidneys, accompanied by
pathological factors such as qi stagnation and damp turbidity. Second-line treatment
patients with advanced colorectal cancer, following first-line chemotherapy or
combined targeted therapy, often present with spleen and stomach deficiency, leading
to inefficient transformation and transportation processes. The spleen has an
inclination toward dryness while detesting dampness, yet internal damp evils
originate and propagate due to the humid climate of the southern region, inducing
internal dampness that exacerbates the deficiency of the spleen, resulting in a
state of spleen deficiency and dampness accumulation within the body. This dampness,
characterized by heaviness and turbidity, manifests as a sensation of head
heaviness, overall lethargy, and heaviness and laziness in the limbs. Dampness,
being a yin evil, easily obstructs the flow of qi and compromises yang qi,
exacerbating spleen deficiency and intensifying the symptoms of deficiency fatigue.
Hence, "spleen deficiency and dampness accumulation" constitute the primary
pathogenesis of CRF in second-line treatment patients with colorectal cancer. The
"Cangpo Liujun Prescription" is a commonly used prescription for the pattern of
spleen deficiency and dampness accumulation, demonstrating certain efficacy in
clinical prevention and treatment of CRF. Composed of Cang Zhu, Hou Po, Chen Pi, Ban
Xia, Dang Shen, Bai Zhu, Fu Ling, and Gan Cao, this formula employs Cang Zhu and Hou
Po to eliminate dampness and fortify the spleen, while Ban Xia and Chen Pi transform
phlegm and regulate qi. Dang Shen, Bai Zhu, Fu Ling, and Gan Cao collectively tonify
the spleen and boost qi, with all eight herbs synergistically promoting spleen
health and dampness transformation, thereby ameliorating CRF-related symptoms. A
preliminary retrospective study involving six patients with colorectal cancer who
underwent first-line treatment and were planned for second-line treatment found that
the Cangpo Liujun Prescription could reduce PFS-R scores, increase KPS scores, and
improve patients' quality of life.
3. The differences in intestinal microbiota among colorectal cancer patients with
different traditional Chinese medicine (TCM) patterns indicate that maintaining the
stability of the microbiota is pivotal for alleviating cancer-related fatigue (CRF)
symptoms.
Research has increasingly shown the relationship between disruptions in the gut
microbiota and various diseases. For instance, compared to healthy individuals, the
abundance of Clostridium and Haemophilus genera is significantly higher in cases of
Qi and Yin deficiency, while Bacteroides, Gemmiger, and Prevotella genera are more
prevalent in patients with Phlegm-Dampness syndrome. Contrasting wet-heat syndrome
with non-wet-heat syndrome individuals reveals a higher abundance of Veillonella,
Coprococcus, and Acidaminococcus genera in the latter. Additionally, studies on a
spleen deficiency rat model demonstrated that intervention with Si-Jun-Zi-Tang
significantly improved symptoms such as eye squinting, hunched back, and lethargy,
potentially by modulating the immune system and gut microbiota (mainly
lactobacillus, Dorea, and Butyricimonas genera).
Comparing late-stage colorectal cancer patients with early-stage ones, the former
exhibit higher spleen deficiency scores, accompanied by a significant increase in
Prevotella, Escherichia-Shigella, and Bacteroides genera, while the abundance of
Clostridium sensu stricto is notably reduced. Furthermore, our team investigated the
differences in intestinal microbiota between colorectal cancer patients with a
deficiency of righteous Qi and those with an abundance of pathogenic factors. We
found that, compared to the healthy control group, the abundance of Clostridium
difficile was reduced in the deficiency of righteous Qi group, while lactobacillus
abundance increased. In contrast, there was a decrease in Prevotellaceae abundance
and a significant increase in Streptococcaceae in the group with an abundance of
pathogenic factors, providing a biological basis for TCM syndrome differentiation
and treatment in colorectal cancer.
Current pharmacological treatments for CRF, such as psychostimulants (e.g.,
methylphenidate), modafinil, paroxetine, and dietary supplements (e.g., coenzyme
Q10, L-carnitine, guarana), have not yet achieved satisfactory efficacy and are
associated with certain side effects. With further research, it has been discovered
that the composition of the intestinal microbiota is closely related to the severity
of CRF. The central nervous system plays a crucial role in inducing CRF. Cancer
cells disrupt the stability of the gut microbiota during their development, and gut
microbiota imbalance can indirectly affect the central nervous system via the
gut-brain axis, further exacerbating CRF. Inflammation may be the primary driving
factor affecting the gut-brain axis. Therefore, maintaining the stability of the
microbiota is crucial for alleviating CRF symptoms. Traditional Chinese medicine
(TCM) and its active ingredients can regulate the composition of the gut microbiota,
thereby influencing the reshaping of the tumor microenvironment in colorectal cancer
treatment, and TCM has indeed been shown to significantly improve CRF-related
symptoms, warranting further investigation.
4. Scientific hypothesis and research significance. Based on the preliminary research
findings and literature review, our team posits a rational hypothesis: the
administration of Cangpo Liujun Prescription (CPLJ) may ameliorate cancer-related
fatigue (CRF) symptoms in advanced colorectal cancer patients with Spleen Deficiency
and Dampness Excess (SDDE) type by rectifying chemotherapy-induced intestinal
microbiota dysbiosis (IFI), thereby reducing the levels of inflammatory factors in
the body and modulating the gut-brain axis (refer to Figure 1). We propose to
include CRF patients with SDDE type late-stage colorectal cancer, randomly assigning
them into two groups (CPLJ group and placebo group), and comparing differences in
patients' Progression-Free Survival-Related (PFS-R) scores, traditional Chinese
medicine syndrome scores, quality of life assessments, immune function tests,
inflammatory factor assays, objective response rates (ORR), disease control rates
(DCR), as well as intestinal microbiota, aiming to offer a novel effective approach
for TCM treatment of CRF in late-stage colorectal cancer, to explore new biomarkers
for CRF and its translational research, and to further enrich the microcosmic
differentiation system of intestinal microbiota in SDDE type late-stage colorectal
cancer patients.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
(1) Diagnosis of stage IV colorectal cancer: confirmed by pathology or cytology; (2)
Second-line treatment; (3) Clinical diagnosis of cancer-related fatigue; (4) Traditional
Chinese medicine syndrome differentiation with spleen deficiency and damp excess; (5) PS
score ≤2; (6) Age of 18-75 years old; (7) Predicted survival time ≥3 months; (8) Without
other serious complications; (9) Non-pregnant and lactating patients; (10) Without
allergic reaction to the ingredients in the prescription; (11) Agreed to participate in
the study after informed consent, signed the informed consent form, and had good
compliance.
Exclusion Criteria:
1) Conditions that may prevent the subjects from completing the clinical trial process,
including but not limited to serious and difficult to control organic lesions or
infection, heart failure, etc.; Patients with severe liver and kidney dysfunction
(serum creatinine ≥1.5 times ULN; ALT or AST≥5 times ULN; Bilirubin ≥1.5 times ULN);
(2) Combined with hematopoietic system diseases, such as anemia, requiring anemia
correction drugs; (3) Receiving or preparing to receive treatment that may affect
CRF; (4) Taking other drugs that may improve CRF; (5) Combined with tumors of other
systems; (6) Mental illness or lack of independent behavior ability; (7) Cooperate
with the investigators to complete the clinical investigation; (8) Pregnant,
preparing to become pregnant or lactating women; (9) Participating in other clinical
trials or have participated in other clinical trials within 3 months; (10) Alcohol
and/or psychoactive substances, substance abusers and addicts; (11) According to the
investigator's judgment, other lesions or conditions that may reduce or complicate
the possibility of enrollment, such as frequent changes in work environment,
unstable living environment, and other conditions that may cause loss to follow-up.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Hangzhou First People' Hospital
Address:
City:
Hangzhou
Zip:
310006
Country:
China
Status:
Recruiting
Contact:
Last name:
Kaibo Guo, Dr.
Phone:
18072946765
Email:
guokaibo@zcmu.edu.cn
Start date:
April 30, 2024
Completion date:
April 1, 2026
Lead sponsor:
Agency:
First People's Hospital of Hangzhou
Agency class:
Other
Source:
First People's Hospital of Hangzhou
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06394128
