ChemotherapyPhase 2NCT05871333
Effect of Losartan on the Incidence and Severity of Chemotherapy-Induced Mucositis in Gastrointestinal Cancer Patients
A Phase 2 study testing Losartan 50mg Tab in people with Chemotherapy and Colorectal Cancer, run by Ain Shams University at 1 site in Egypt.
Trial summary
Mucositis is a common and clinically significant side effect of both anticancer chemotherapy and radiation therapy that can affect any portion of the gastrointestinal tract. Not only associated with an adverse symptom profile, but also it may limit patients' ability to tolerate treatment if not adequately prevented… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chemotherapy, Colorectal Cancer, Intestinal Mucositis
- What is being tested?
- Losartan 50mg Tab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteEgypt
- Study dates
- 17 Jul 2023to 1 Jul 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients aged 18 years old or more.
- Patients diagnosed with gastrointestinal cancer eligible for chemotherapy
- Eastern Cooperative Oncology Group (ECOG) performance ≤ 2.
- Platelet count more than 100 × 10^9/L.
- Absolute neutrophil count: greater than 1.5 × 10^9/L.
- Aspartate aminotransferase level up to 2.5 times the upper limit normal.
- Serum bilirubin level not more than 1.5 times the institutional upper limit normal.
- Serum creatinine levels up to 1.5 mg% and 1.4 mg% for males and females respectively.
Who cannot join
- Currently taking an angiotensin converting enzyme inhibitor (ACEi) or Angiotensin receptor blocker (ARB)
- Prior reaction or intolerance to an ARB or ACE inhibitor, including but not limited to angioedema.
- Pregnant or breastfeeding women.
- Females in child bearing age not currently taking a protocol allowed version of contraception: intrauterine device, Depo-formulation of hormonal contraception.
- Patient reported history or electronic medical record history of kidney disease, defined as:
- Any history of dialysis. History of chronic kidney disease stage IV. Estimated Glomerular Filtration Rate (eGFR) of < 30ml/min/1.73 m2 Other Kidney disease that in the opinion of investigator, would affect Losartan Clearance.
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- Patient reported dehydration and significantly decreased urine output in the past 72 hours.
- Most recent systolic blood pressure prior to enrollment <110 mmHg.
- Current participation in any other clinical investigation.
- Currently taking any drug contraindicated with Losartan administration.
Trial locations and contacts
1 site in 1 country.
About this study
Mucositis is a common and clinically significant side effect of both anticancer chemotherapy and radiation therapy that can affect any portion of the gastrointestinal tract. Not only associated with an adverse symptom profile, but also it may limit patients' ability to tolerate treatment if not adequately prevented and managed. Moreover, it may be associated with secondary local and systemic infection and poor health outcomes, and generates additional use of healthcare resources resulting in additional costs.
Based on study of 38 patients of mean age sixty-one years old diagnosed with colorectal carcinoma were included to evaluate gastrointestinal adverse effect with different schedules of FOLFOX. Incidence of oral mucositis with FOLFOX-4 Is 76%, FOLFOX-6 is 62%, mFOLFOX-6 is 79% and FOLFOX-7 is 93%
Read more
Chemotherapy-induced mucositis is commonly described as a five-phase sequence:
initiation (0-2 days),upregulation and activation of messengers (2-3 days), signal amplification (2-5 days), ulceration with inflammation (5-14 days) and healing (14-21 days)
According to the model introduced by some studies the primary inducer involved in unleashing mucosal injury upon chemotherapy is the production of reactive oxygen species (ROS), leading to tissue inflammation and mucositis induction.
Inflammatory signaling pathways are upregulated during high reactive oxygen species states which further contribute to cytotoxicity. leading to the third step in the oral mucositis pathway. In this inflammatory phase, cytokines including Tissue Necrosis Factor alpha (TNF-α), prostaglandins, Nuclear factor Kappa β (NF-кβ), and interleukin (IL) 1β are released.
The cytotoxic effects of chemotherapy, inflammation, and reactive oxygen species-mediated DNA damage result in gradual apoptosis of mucosal epithelial cells. Ulcerative sites become relatively neutropenic which predisposes them to bacterial and yeast infections. These bacterial toxins further simulate the underlying inflammatory state through release of additional cytokines.
It is necessary to emphasize that oral mucositis is frequently documented only in its advanced phases owing to the requirements for clinical therapy and assistance. Therefore, the search for new active ingredients that could be used in the prevention (and even treatment) of oral and intestinal mucositis is of utmost importance.
Read the detailed description
in this study Losartan, a AT1 angiotensin 2 receptor blockers (ARB), used clinically for antihypertensive purposes, has anti-inflammatory effects widely described in the literature.
Losartan has been shown to reduce pro-inflammatory cytokines, such as TNF-α, IL-1β, IL-6, and the activation of nuclear transcription factor (NF-κB), in addition to an antioxidant effect in different inflammatory diseases as neuropathic pain in patients with paclitaxel- induced peripheral neuropathy.
Studies have already shown that angiotensin 2 pathway modulators have a protective effect on oral and intestinal mucositis in rats.
Patients meeting the study inclusion criteria will be educated firmly about the disease details and all information about the drug, then will be assigned to one of two groups, the control group or the intervention group.
The two groups will undergo baseline evaluation at the beginning of the study including Demographic data collection: Age, gender, weight, height, BSA, Risk factors related to mucositis, Medical history and Comorbidities reporting as HTN, DM and others, Vital signsas Blood pressure and pulse recording, Social history and Smoking status and Clinical assessment for confirmation of absence of mucositis and examination of oral mucous membrane and gut functions (bowel habits) Weekly for assessment of the following: occurrence and severity of OM and IM, Pain assessment will be done using the NRS score and through patient interview, occurrence and severity of dysphagia and Need for supportive management e.g. Painkillers and anti-diarrhea.
Every cycle for the need for hospitalization due to oral or intestinal symptoms or any unplanned chemotherapy breaks due to oral or intestinal toxicity in both groups.
In between cycles via phones for any side effects encountered by patients in both groups due to the administered drug (Losartan). Patients will be given a side effects reporting card for follow up if any side effect occurred during treatment. And Quality of Life assessment by Functional Assessment of Cancer Therapy- General (FACT-G).
By the end of cycle 8, all patients in both groups will be reassessed for all laboratory and clinical evaluations.
- Conditions
- Chemotherapy, Colorectal Cancer, Intestinal Mucositis, Oral Mucositis
- Being tested
- Losartan 50mg Tab
- Keywords
- Losartan, Colorectal Cancer, Chemotherapy-Induced Mucositis
- Medical subject headings
- Colorectal Neoplasms, Stomatitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Losartan 50mg TabDrug
Also called Angiotension receptor blockers
Losartan 50 mg oral tablets
| Study group | Role | What they receive |
|---|---|---|
| Standard of care | No intervention | Patients will receive FOLFOX-6 regimen consisted of 2-hour infusion of oxaliplatin (100 mg/m2) and 2-hour infusion of leucovorin (400 mg/m2) on Day 1, followed by 5-fluorouracil (5-FU) bolus (400 mg/ m2) on Day 1 and 46-hour infusion (2.4 g/m2) with cycle repeated every 2 weeks over range of 20-24 weeks depending on patients disease state. |
| standard of care + Losartan | Experimental | Patients will receive FOLFOX-6 regimen consisted of 2-hour infusion of oxaliplatin (100 mg/m2) and 2-hour infusion of leucovorin (400 mg/m2) on Day 1, followed by 5-fluorouracil (5-FU) bolus (400 mg/ m2) on Day 1 and 46-hour infusion (2.4 g/ m2) with cycle repeated every 2 weeks over range of 20-24 weeks depending on patients disease state. In addition to Losartan 50 mg/day orally for 4 months. Receives: Drug: Losartan 50mg Tab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Occurrence of oral mucositis
Assessment the occurrence of oral mucositis by physical examination of oral cavity
Measured: monthly for 6 months
change in Severtity of Oral Mucositis
Assessment of the severity of oral mucositis using the national cancer institute common
Measured: monthly for 6 months
change in severity of intestinal mucositis
assessment of the severity of oral mucositis using the national cancer institute terminology criteria version 5.0
Measured: monthly for 6 months
Secondary outcomes (4)
Evaluation of cancer control by Ultrasound
Disease control will be assessed by US
Measured: at Baseline and at week 24 ( end of study)
Quality of life questionnaire
Adverse events encountered by patients in both groups, need for hospitalization due to oral and/or intestinal symptoms and unplanned chemotherapy breaks due to oral and/or intestinal toxicity will be recorded on weekly bases.
Measured: monthy for 6 months
Laboratory evaluation of TNF-α level
Change in Tumor necrosis factor-a (TNF-α).
Measured: baseline and at week 16
Laboratory evaluation of Interleukin-1β level
Change in Interleukin-1β.
Measured: Baseline and at week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2023
- Study start17 Jul 2023 (estimated)
- Primary completion1 Jun 2024 (estimated)
- Study completion1 Jul 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ChemotherapyStudies of the same condition, open and under way.
- More trials run by Ain Shams UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Group I: Patients will receive only their standard therapy for 4 months. Group II: will receive the studied drug orally in addition to their standard therapy
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ain Shams University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Amira Yousry, Ain Shams University
- Investigators
- Amira Y mohamed, Principal investigator, Ain Shams University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05871333
- Sponsor's protocol ID
- Losartan, Mucositis
- Status last verified
- Jul 2023
- First submitted
- 15 Mar 2023
- Last updated
- 19 Jul 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Losartan on the Incidence and Severity of Chemotherapy-Induced Mucositis in Gastrointestinal Cancer Patients
- ClinicalTrials.gov ID
- NCT05871333
- Acronym / sponsor ID
- Losartan, Mucositis
- Conditions
- Chemotherapy, Colorectal Cancer, Intestinal Mucositis, Oral Mucositis
- Keywords
- Losartan, Colorectal Cancer, Chemotherapy-Induced Mucositis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Ain Shams UniversityUniversity, hospital or other
- Study start
- 17 Jul 2023 (estimated)
- Primary completion
- 1 Jun 2024 (estimated)
- Study completion
- 1 Jul 2024 (estimated)
- First posted
- 23 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Mucositis is a common and clinically significant side effect of both anticancer chemotherapy and radiation therapy that can affect any portion of the gastrointestinal tract. Not only associated with an adverse symptom profile, but also it may limit patients' ability to tolerate treatment if not adequately prevented and managed. Moreover, it may be associated with secondary local and systemic infection and poor health outcomes, and generates additional use of healthcare resources resulting in additional costs.
Based on study of 38 patients of mean age sixty-one years old diagnosed with colorectal carcinoma were included to evaluate gastrointestinal adverse effect with different schedules of FOLFOX. Incidence of oral mucositis with FOLFOX-4 Is 76%, FOLFOX-6 is 62%, mFOLFOX-6 is 79% and FOLFOX-7 is 93%
Chemotherapy-induced mucositis is commonly described as a five-phase sequence:
initiation (0-2 days),upregulation and activation of messengers (2-3 days), signal amplification (2-5 days), ulceration with inflammation (5-14 days) and healing (14-21 days)
According to the model introduced by some studies the primary inducer involved in unleashing mucosal injury upon chemotherapy is the production of reactive oxygen species (ROS), leading to tissue inflammation and mucositis induction.
Inflammatory signaling pathways are upregulated during high reactive oxygen species states which further contribute to cytotoxicity. leading to the third step in the oral mucositis pathway. In this inflammatory phase, cytokines including Tissue Necrosis Factor alpha (TNF-α), prostaglandins, Nuclear factor Kappa β (NF-кβ), and interleukin (IL) 1β are released.
The cytotoxic effects of chemotherapy, inflammation, and reactive oxygen species-mediated DNA damage result in gradual apoptosis of mucosal epithelial cells. Ulcerative sites become relatively neutropenic which predisposes them to bacterial and yeast infections. These bacterial toxins further simulate the underlying inflammatory state through release of additional cytokines.
It is necessary to emphasize that oral mucositis is frequently documented only in its advanced phases owing to the requirements for clinical therapy and assistance. Therefore, the search for new active ingredients that could be used in the prevention (and even treatment) of oral and intestinal mucositis is of utmost importance.
Detailed description
in this study Losartan, a AT1 angiotensin 2 receptor blockers (ARB), used clinically for antihypertensive purposes, has anti-inflammatory effects widely described in the literature.
Losartan has been shown to reduce pro-inflammatory cytokines, such as TNF-α, IL-1β, IL-6, and the activation of nuclear transcription factor (NF-κB), in addition to an antioxidant effect in different inflammatory diseases as neuropathic pain in patients with paclitaxel- induced peripheral neuropathy.
Studies have already shown that angiotensin 2 pathway modulators have a protective effect on oral and intestinal mucositis in rats.
Patients meeting the study inclusion criteria will be educated firmly about the disease details and all information about the drug, then will be assigned to one of two groups, the control group or the intervention group.
The two groups will undergo baseline evaluation at the beginning of the study including Demographic data collection: Age, gender, weight, height, BSA, Risk factors related to mucositis, Medical history and Comorbidities reporting as HTN, DM and others, Vital signsas Blood pressure and pulse recording, Social history and Smoking status and Clinical assessment for confirmation of absence of mucositis and examination of oral mucous membrane and gut functions (bowel habits) Weekly for assessment of the following: occurrence and severity of OM and IM, Pain assessment will be done using the NRS score and through patient interview, occurrence and severity of dysphagia and Need for supportive management e.g. Painkillers and anti-diarrhea.
Every cycle for the need for hospitalization due to oral or intestinal symptoms or any unplanned chemotherapy breaks due to oral or intestinal toxicity in both groups.
In between cycles via phones for any side effects encountered by patients in both groups due to the administered drug (Losartan). Patients will be given a side effects reporting card for follow up if any side effect occurred during treatment. And Quality of Life assessment by Functional Assessment of Cancer Therapy- General (FACT-G).
By the end of cycle 8, all patients in both groups will be reassessed for all laboratory and clinical evaluations.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Group I: Patients will receive only their standard therapy for 4 months. Group II: will receive the studied drug orally in addition to their standard therapy
| Arm | Type | Receives |
|---|---|---|
| Standard of care | No intervention | –Patients will receive FOLFOX-6 regimen consisted of 2-hour infusion of oxaliplatin (100 mg/m2) and 2-hour infusion of leucovorin (400 mg/m2) on Day 1, followed by 5-fluorouracil (5-FU) bolus (400 mg/ m2) on Day 1 and 46-hour infusion (2.4 g/m2) with cycle repeated every 2 weeks over range of 20-24 weeks depending on patients disease state. |
| standard of care + Losartan | Experimental | Drug: Losartan 50mg TabPatients will receive FOLFOX-6 regimen consisted of 2-hour infusion of oxaliplatin (100 mg/m2) and 2-hour infusion of leucovorin (400 mg/m2) on Day 1, followed by 5-fluorouracil (5-FU) bolus (400 mg/ m2) on Day 1 and 46-hour infusion (2.4 g/ m2) with cycle repeated every 2 weeks over range of 20-24 weeks depending on patients disease state. In addition to Losartan 50 mg/day orally for 4 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male or female patients aged 18 years old or more.
- Patients diagnosed with gastrointestinal cancer eligible for chemotherapy
- Eastern Cooperative Oncology Group (ECOG) performance ≤ 2.
- Platelet count more than 100 × 10^9/L.
- Absolute neutrophil count: greater than 1.5 × 10^9/L.
Key exclusion criteria (10 listed)
- Currently taking an angiotensin converting enzyme inhibitor (ACEi) or Angiotensin receptor blocker (ARB)
- Prior reaction or intolerance to an ARB or ACE inhibitor, including but not limited to angioedema.
- Pregnant or breastfeeding women.
- Females in child bearing age not currently taking a protocol allowed version of contraception: intrauterine device, Depo-formulation of hormonal contraception.
- Patient reported history or electronic medical record history of kidney disease, defined as:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Losartan 50mg TabAlso: Angiotension receptor blockersLosartan 50 mg oral tablets | Drug | standard of care + Losartan |
Primary outcome
Change in Occurrence of oral mucositis
Time frame: monthly for 6 months
Assessment the occurrence of oral mucositis by physical examination of oral cavity
change in Severtity of Oral Mucositis
Time frame: monthly for 6 months
Assessment of the severity of oral mucositis using the national cancer institute common
change in severity of intestinal mucositis
Time frame: monthly for 6 months
assessment of the severity of oral mucositis using the national cancer institute terminology criteria version 5.0
4 secondary outcomes
Evaluation of cancer control by Ultrasound
Time frame: at Baseline and at week 24 ( end of study)
Quality of life questionnaire
Time frame: monthy for 6 months
Laboratory evaluation of TNF-α level
Time frame: baseline and at week 16
Laboratory evaluation of Interleukin-1β level
Time frame: Baseline and at week 16
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jul 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amira Y mohamed principal investigator
Ain Shams University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Losartan 50mg Tab in people with Chemotherapy and Colorectal Cancer, run by Ain Shams University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Amira Y Mohamed (01020435341, amira.yousry@pharma.asu.edu.eg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Occurrence of oral mucositis (time frame: monthly for 6 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jul 2023.