Overview
- People with colorectal cancer who are scheduled to undergo colorectal surgery are eligible to participate in the LEONORA study.
- It is important that this surgery take place at a hospital participating in the LEONORA study.
- Colorectal cancer patients at all stages of the disease are eligible to participate.
- In this study, researchers are investigating whether a synbiotic can alleviate gastrointestinal symptoms following colorectal cancer surgery. Synbiotics are a combination of gut bacteria and the dietary fiber that serves as food for these bacteria.
Study status: The study is currently enrolling patients (recruitment open).
Colorectal cancer is one of the most common cancers worldwide. It is often treated with surgery, during which doctors remove the tumor and surrounding intestinal tissue.
Patients often also receive chemotherapy or antibiotics as part of their treatment. Both of these treatments severely disrupt the natural gut flora.
Due to treatment, people with colorectal cancer often suffer from gastrointestinal symptoms during and even long after treatment. The most common symptoms include:
- chronic diarrhea
- abdominal pain
- constipation
This can reduce quality of life and limit participation in daily activities.
To alleviate symptoms, it may help to support beneficial gut bacteria. The goal is to restore the natural balance of bacteria in the gut. Studies have shown that synbiotics can support this process.
A synbiotic consists of two components:
- A probiotic:These are live bacteria that occur naturally in the gut. They support healthy gut function.
- A prebiotic: These are dietary fibers that serve as food for bacteria in the gut and help them establish natural colonies.
Synbiotics can therefore influence the composition of the various bacteria in the gut and thus promote gut health.
Initial laboratory experiments and observational studies show that synbiotics may have additional beneficial effects—by influencing the immune system, they may potentially prevent cancer and support cancer treatments.
The researchers in the LEONORA study aim to investigate whether taking synbiotics alleviates gastrointestinal symptoms following colorectal cancer surgery. In addition, they are studying how this affects the quality of life and survival of colorectal cancer patients.
- For more details on the specific goals the scientists are pursuing with the LEONORA study, see the section “What is the goal of the LEONORA study?”.
The English title of the LEONORA study is: “Lower gastrointestinal symptom burden by prophylaxis with synbiotics after colorectal cancer surgeries”
This means:
- Researchers are testing beneficial bacteria for a healthy gut microbiota.
- They are investigating whether this improves people’s quality of life after colorectal cancer surgery.
Objectives of the LEONORA study
The LEONORA study investigates whether patients experience fewer gastrointestinal symptoms after colorectal cancer surgery if they take a synbiotic. Synbiotics contain beneficial gut bacteria and dietary fiber that support the growth of these bacteria. The researchers are examining whether this improves the participants’ quality of life.
In the study, they are comparing the group taking the synbiotic with a control group. The researchers aim to determine the effects of taking synbiotics during the first 90 days following surgery. They are also monitoring potential long-term effects.
In doing so, the study team is collecting data on:
- Certain blood levels that indicate inflammation in the body (inflammatory markers).
- Any infections or other illnesses that occur.
- Overall survival and recurrence-free survival.
- How the composition of gut bacteria changes.
- The participants’ quality of life (in general and regarding gastrointestinal symptoms).
Who is the study suitable for?
Patients who meet all the following criteria are eligible to participate in the LEONORA study:
- Patients have colorectal cancer.
- The patient is at least 18 years old.
- Surgery for colorectal cancer is scheduled within the next 14 days. It is important that the surgery be scheduled at a hospital participating in the LEONORA study. Information on participating hospitals can be found in the section “Where is the study conducted?”.
- All patients must sign a written informed consent form to participate in the LEONORA study.
- Patients must be willing to complete a questionnaire and provide a blood sample and a stool sample before surgery. Alternatively, doctors may take a rectal swab if bowel movements are problematic.
Patients cannot participate in the study if any of the following apply:
- The study team believes that patients may not be able to reliably participate in the study—for example, because they do not sufficiently understand the study information, are not willing to fully participate in the study, or are unlikely to be easily reachable after being discharged from the hospital.
- The participant has already taken part in the LEONORA study.
- The patient is already participating in another clinical trial that is evaluating treatments or medications that affect nutrition.
- The patient is pregnant.
- The patient is taking medications that suppress the immune system. Exceptions to this are chemotherapy and radiation therapy administered before or after surgery.
- The patient has diabetes and is being treated with insulin.
The LEONORA study is a:
- Multicenter study: Patients can participate at various study centers in Germany.
- Randomized study: In a randomized study, participants are randomly assigned to receive either the synbiotic or the placebo. This allows the results to be evaluated as objectively as possible.
- Double-blind study: Neither the participants nor the researchers know which participants are receiving the study drug and which are receiving the placebo. This helps the study team obtain results that are as unbiased as possible.
- Phase III trial: In a Phase III trial, researchers test whether the investigational drug is more effective than the comparator treatment.
(1) Participant selection and pre-treatment consultation
The study team at the participating clinics assesses whether patients are eligible to participate in the LEONORA study. The study physicians conduct a detailed information session with the patients and explain the details of participation in the study to them. Patients who decide to participate in the study following the informational meeting must sign an informed consent form.
(2) Before treatment begins
Before treatment begins, physicians collect study-relevant information regarding the participants’ health. This includes, for example:
- A questionnaire about the patient’s quality of life (as it relates to gastrointestinal symptoms). Information is also collected on previous treatments, diet, physical activity, and other factors that may influence the colorectal cancer patient’s health.
- A blood sample and a stool sample. Patients can collect the stool sample by themselves at home or at the clinic.
The examinations take place during the 2 weeks prior to colorectal cancer surgery.
Participants are randomly assigned to either the treatment group or the control group. This is also known as randomization.
(3) Colorectal Cancer Surgery
Patients undergo surgery. Their treating physicians will explain how the surgery will be conducted.
(4) Treatment phase
After colorectal cancer surgery, the patient remains in the hospital. During this time, the study team closely monitors the patient’s health.
The doctors document the patient’s progress, any symptoms that may arise, and whether the participants are taking the medications correctly.
Throughout the entire treatment period, patients are asked to keep a study diary. In this diary, they record when they took the two study medications along with any symptoms or other medical conditions that arise.
Treatment with the first study medication begins as soon as patients can consume liquid food again. This is usually possible 1–3 days after surgery.
First phase (Week 1 to Week 12):
Depending on the random assignment, participants will receive either a probiotic or a placebo. Half of the participants will receive the probiotic.
- Probiotics contain live bacteria that are “beneficial” to the gut.
- The placebo contains mannitol, a sugar that has no effect on the existing gut bacteria.
Participants take both in capsule form.
About 4 weeks after surgery, participants will complete a second questionnaire. They will also submit a second stool sample. Patients will receive questionnaires and stool collection kits by mail.
Second Phase (Week 5 to Week 12):
Four weeks after surgery, participants also take a prebiotic. This consists of dietary fiber inulin. It helps beneficial bacteria colonize the gut. Participants start this treatment later because prebiotics can cause bloating. Immediately after surgery, bloating could cause pain during wound healing. As an additional precaution, the prebiotic is initially administered at such a low dose that bloating is unlikely to occur.
The dose is increased every 2 weeks because the bacteria (which process the prebiotic) multiply in the gut. Previous studies have shown that this slow, gradual increase in dosage can prevent the occurrence of bloating.
Participants who have already received a placebo instead of the probiotic will also receive a placebo prebiotic. This contains maltodextrin, a sugar that has no effect on the bacteria in the gut.
The study team measures out and packages the prebiotic in powder form. They do the same with the “dummy prebiotic” (placebo). Study participants dissolve the powder in a beverage and drink it daily. Along with this beverage, they also take the capsule containing the study preparation (probiotic or placebo).
To allow the gut to adjust gradually and minimize any discomfort, the fiber dose in the prebiotic is increased every 2 weeks until the study ends in week 12. The study team measures out and packages the correct amount for the participants.
(5) End of the LEONORA study (final visit)
Treatment as part of the LEONORA study ends approximately 3 months after colorectal cancer surgery. At that time, patients must submit another stool sample and another blood sample. Blood drawing can take place either at the study center or at the patient’s primary care physician’s office.
In addition, the study team requires the third completed questionnaire as well as the participant’s study diary.
(6) Follow-up
For up to 2 years after colorectal cancer surgery, the study team collects data on the patients. This includes stool samples at 6 and 12 months, as well as quality-of-life questionnaires at 6, 12, and 24 months after enrollment in the LEONORA study. The stool sample collection kits and the quality-of-life questionnaires are sent by mail.
After 6 months, the participants’ primary care physicians and/or oncologists will also be contacted. This allows the study team to gather information about hospitalizations, infections, and the further course of the colorectal cancer and its treatment.
These are the potential benefits of participating in the LEONORA study:
- Taking synbiotics may help the gut flora recover more quickly after treatment. A synbiotic contains both beneficial bacteria and dietary fiber, thereby supporting gut health.
- Researchers believe this could also improve quality of life, particularly regarding gastrointestinal symptoms.
- The treatment may also help symptoms caused by cancer therapy and surgery subside more quickly.
- By participating in the LEONORA study, patients can help improve treatment for future colorectal cancer patients.
However, participating in the LEONORA study may also have some drawbacks:
- Taking prebiotics may cause bloating.
- Half of the participants will receive a placebo during the study. If the study medication has the expected benefits, they will not be able to benefit from it.
- The blood draws performed as part of the study may be associated with minor risks—such as bruising, bleeding, or mild pain. The study physicians will provide information about any additional risks.
Where is the study being conducted?
The LEONORA study is taking place at the NCT study centers in Heidelberg, Tübingen, Stuttgart, Cologne, Essen, Berlin, and Augsburg.
In addition, colorectal cancer patients can participate at the following collaborating hospitals:
- Frankfurt University Hospital
- University Medical Center Giessen & Marburg (Giessen campus)
An overview of the hospitals participating in LEONORA can be found on the website of the German Registry of Clinical Trials (under “Recruitment Sites”).
What costs will participants incur?
Participation in the study is free of charge for patients. However, you will not receive any compensation for your time or expenses. Travel expenses are not reimbursed as part of the study.
If you have any questions about the study’s funding, you can ask the study team, for example during the pre-treatment consultation.
How many participants will the study accept? Are there still places available?
In total, the LEONORA study will enroll 206 patients. Of these, 103 participants will receive the synbiotic and 103 participants will receive the placebo. The study is expected to continue enrolling participants until September 2027.
Scientific publications (selection)
Theodoropoulos, G. E., Memos, N. A., Peitsidou, K., Karantanos, T., Spyropoulos, B. G., & Zografos, G. (2016). Synbiotics and gastrointestinal function-related quality of life after elective colorectal cancer resection. Annals of gastroenterology, 29(1), 56–62 https://doi.org/10.20524/aog.2016.0018
Amitay, E. L., Carr, P. R., Gies, A., Laetsch, D. C., & Brenner, H. (2020). Probiotic/Synbiotic Treatment and Postoperative Complications in Colorectal Cancer Patients: Systematic Review and Meta-analysis of Randomized Controlled Trials. Clinical and translational gastroenterology, 11(12), e00268. https://doi.org/10.14309/ctg.0000000000000268
This study description was prepared by authors from the Cancer Information Service, under the direction of Dr. S. Weg-Remers, based on the study documentation.