Trial Title:
Probiotics for Depression in Cancer Patients
NCT ID:
NCT06496438
Condition:
Depression
Anxiety Disorder
Probiotics
Gastrointestinal Cancer
Quality of Life
Chemotherapy
Conditions: Official terms:
Gastrointestinal Neoplasms
Depression
Depressive Disorder
Anxiety Disorders
Conditions: Keywords:
Randomized Clinical Trial
Gastrointestinal Cancer
Chemotherapy
Psychobiotics
Depression
Anxiety
Quality of life
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Supportive Care
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Intervention:
Intervention type:
Dietary Supplement
Intervention name:
Psychobiotics
Description:
Dietary Supplement: A four probiotic regime, containing Lactobacillus rhamnosus,
Bifidobacterium animalis subsp. lactis, Bifidobacterium breve, and Bifidobacterium longum
at a concentration of 1, 000,000,000 CFU.
Arm group label:
Psychobiotics
Intervention type:
Other
Intervention name:
Placebo
Description:
The placebo regime, containing powdered glucose polymer, will be identical in packaging,
appearance, consistency, and solubility in drinking water, thus making it impossible to
recognize which are placebo and which the therapeutic formulation. Both will be
identically standardized by the same pharmaceutical company [Uni-Pharma, Greece].
Arm group label:
Placebo
Summary:
Anxiety and depressive disorders are quite prevalent in the general population. In 2015,
it was estimated that 3.6% of the world population (around 264 million individuals) live
with depression and 4.4% (around 322 million) with anxiety, while in the recent years of
the COVID-19 pandemic, the prevalence of these disorders has significantly increased.
According to the American Psychiatric Association, in 2013 depression was defined as a
serious mental illness characterized by decreased mood lasting more than 15 days, a lack
of interest, and (even) apathy to normal daily activities. Depression, particularly in
its severe form - the major depressive disorder (MDD), is the second leading cause of
disability and the most common emotional disorder.
Recent research data indicate that this psychiatric disorder, as also similar
neuropsychological conditions (Parkinson's, autism, etc.) have, as their main substrate,
a disturbance in the diversity of the gut microbiome. More specifically, it has been
shown that there is a direct and bidirectional communication between gut and brain - the
"gut-brain-axis". The gut, through its microbiome, communicates with the brain by means
of neural, immunological, and metabolic pathways, either directly, through the vagus
nerve or indirectly, either through the microbiome immunomodulation or the tryptophan
pathway, or by the production of various neuroactive molecules.
The disturbance in the diversity of the gut microbiome, termed dysbiosis, involves
changes in the composition and the number of bacteria genera; and is causatively related
to depression via the gut-brain axis. The transmission of nerve impulses, both via the
hypothalamic-pituitary-adrenal axis and via the vagus nerve is disrupted by dysbiosis,
leading to anxiety and depression, or, conversely, stressful conditions, more
particularly emotional stress, which triggers an imbalance in the
hypothalamic-pituitary-adrenal axis, leading to systemic immune responses and intestinal
dysbiosis. This imbalance can clinically manifest with alterations in digestive tract
function, knowledge accepted since the beginning of the previous century.
Nowadays, there is considerable evidence that the gut microbiome represents a novel
anti-depressant and the term "psychobiotics" has been used to describe those species of
probiotic bacteria excreting mental health benefits.
Certain Bifidobacterium and Lactobacillus species have already demonstrated, both
experimentally and in clinical studies, their capability to improve mood, reduce anxiety,
and enhance cognitive function. On these grounds, it is reasonable to raise the
hypothesis that, by restoring the diversity of the gut microbiome, and thus enhancing the
population of these specific probiotic species - termed 'psychobiotics', due to their
specified functions, - could at least lead to an improvement in neuro-psychological
disorders through gut-brain-axis remodeling.
Detailed description:
Based on the assumption that 1. at least one third of digestive cancer patients operated
on - and probably more, when surgery is followed by chemotherapy sessions - suffer from
anxiety and depression, 2. psychobiotics can beneficially modify the gut microbiome, 3.
psychobiotics can improve the mental health of patients suffering from depression, and 4.
there is no other study on the use of psychobiotics in anxiety and/or depression symptoms
in patients operated on for digestive tract malignancies and subjected to chemotherapy
thereafter the present study was designed to investigate the ability of a probiotic
formulation containing bacteria with known psychobiotic properties to change the
depression and anxiety status of digestive cancer patients undergoing chemotherapy
postoperatively.
This study will be a prospective, double-blind, randomized study against placebo in
patients operated on for digestive cancer and undergoing chemotherapy. The study will be
conducted in the 1st Surgical Department of the Aristotle University of Thessaloniki, at
the AHEPA University Hospital of Thessaloniki, Greece, in collaboration with the
Outpatient Surgical Oncology Unit. Permission has already been obtained from the
Scientific Council of the AHEPA Hospital (Approval Number: 313/4.7.2023).
The oncologist involved in the study protocol will be responsible for randomization. She
will inform the patients who meet the study entry criteria of the purpose of the study,
and receiving their written consent after detailed information. Patients having signed
the informed consent will then be assigned at random [in a 1:1 ratio] to receive placebo
or probiotic regime treatment, according to a computer-based table [randomized.com]. The
randomization will be blinded to the study statistician, as well as to the physicians in
contact with patients for interviews to facilitate the collection of answers to the
questionnaires. Sealed envelops will be used to ensure blinding. Only the study
coordinator will be aware of the content, having no further involvement with the
patients. Each patient, having signed the consent, will then receive a unique
code-number, being a combination of the anatomical location of the tumor, the patient's
serial number, a capital letter A or B - blindly indicating the treatment groups - and a
small letter, [a,b,c] indicating the physician who contacts each patient.
After patient aggrees to be included in the study, the demographic data that will be
obtained in relation to each patient are: gender; age; body weight (in kilograms) and
height (in meters) to calculate BMI; reported weight loss in kilograms since the disease
diagnosis; marital status; smoking habits (no smoking or number of cigarettes/day);
alcohol consumption (type and volume); and the possible use of tranquilizers [mg of
active substance]. Optionally, patients will give information as to their educational
level (1st, 2nd, or 3rd grade), annual income (<10.000€, 10.001-30.000€, >30.001€/year);
and health care insurance (public, private, both). From their medical records cancer type
and anatomical localization; cancer stage (TNM classification); type of surgical
intervention; and co-morbidity indices (Charlson Comorbidity Index) will be obtained.
Additional information will be collated relating to the time lapse since diagnosis (in
days); the time lapse from hospital discharge to starting chemotherapy (in days); and the
time from starting chemotherapy to study entry (in days).
The probiotic regime under testing is a combination of 4 psychobiotics: Lactobacillus
rhamnosus, Bifidobacterium animalis subsp. lactis, Bifidobacterium breve, and
Bifidobacterium longum, at a dose of 1.000.000.000/CFU. These for psychobiotics are the
main ingredients of the commercially available formula LactoLevure®, ProbioMood
[UniPharma, Athens, Greece], which also contains saffron and magnesium. This formula is
marketed for "people with an anxious lifestyle who often suffer from symptoms such as low
mood or fatigue as a result of stress".
The placebo regime, containing powdered glucose polymer, will be identical in packaging,
appearance, consistency, and solubility in drinking water, thus making it impossible to
recognize which are placebo and which the therapeutic formulation. Both will be
identically standardized by the same pharmaceutical company [Uni-Pharma, Greece].
Patients will be administered the "treatment" or the placebo daily - one sachet twice a
day, two hours after breakfast, for 30 consecutive days. At the follow-up appointment
after treatment termination, patients will be required to return any remaining sachets
which they forgot to take [Patients will be telephoned to remind a day before
appointment). Fifteen days after the start of treatment, there will be telephone contact
(or a face-to-face contact if the new chemotherapy appointment coincides) for the purpose
of a rough, out of the protocol assessment of the patient's condition by the same
physician who conducted the initial interview; the purpose being to confirm that the
patient is receiving the treatment and to un-officially obtain information on whether
he/she is generally feeling better than previously.
Two follow up evaluations will be held 1 month and 3 months, after treatment begins.
Patients will be evaluated by means of standardized questionnaires - officially
translated and validated in the Greek language - for the quantification of depression,
emotional state, anxiety, quality of life, physical weakness and pain.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Age >18 and <85
- Histologically confirmed diagnosis of digestive tract malignancy, the tumor having
been surgically resected and the patient currently undergoing chemotherapy sessions
- Informed consent obtained to participate in the study
Exclusion Criteria:
- Not understanding the Greek language
- Dementia
- Pre-existing psychiatric disorders
- Already receiving probiotic supplements (apart from yoghurt)
- Participation in another clinical trial
- Consumption of less than the 90% of treatment sachets/doses (verified by the sachets
returned)
- Those having received during hospitalization other probiotic formulations
Gender:
All
Minimum age:
18 Years
Maximum age:
85 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
AHEPA University Hospital
Address:
City:
Thessaloníki
Zip:
54636
Country:
Greece
Status:
Recruiting
Contact:
Last name:
Katerina Kotzampassi, Dr.
Email:
kakothe@yahoo.com
Start date:
November 15, 2023
Completion date:
March 15, 2025
Lead sponsor:
Agency:
Aristotle University Of Thessaloniki
Agency class:
Other
Source:
Aristotle University Of Thessaloniki
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06496438
