CancerPhase 4NCT03145012
Histamine Receptor 2 Antagonists as Enhancers of Anti-Tumour Immunity
A Phase 4 study testing Ranitidine in people with Cancer, run by Nova Scotia Health Authority at 1 site in Canada.
Trial summary
The immune response against tumors can be highly effective in preventing tumor development, growth and metastasis under certain circumstances. However, tumor associated immune suppression can profoundly limit the impact of natural tumor immunity and also reduce the effectiveness of tumor immunotherapy strategies. Read more about this study
- Who is it for?
- Ages 20 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Cancer
- What is being tested?
- Ranitidine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteCanada
- Study dates
- 1 May 2018to 24 Oct 2018
- Phase
- Phase 4
- 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 20 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age 20-50 years old, all sexes or genders
- Veins acceptable for blood draw
- Able to provide informed consent
- eGFR > 90 mL/min/1.73m2
- Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on physical examination and/or clinical laboratory evaluations (hematology, biochemistry, ECG, urinalysis). Clinical laboratory values within stated normal range; if not within this range, they must be without clinical significance
- Female volunteers who are of childbearing potential that agree to use of the accepted contraceptive regimens from at least 21 days prior to the first administration of study drug, during the study, and for at least 30 days after the last dose of study drug
- Female volunteers who are postmenopausal (no menses for at least 1 year, or surgically sterile
Who cannot join
- Use of ranitidine for greater than 1 week within 6 months of starting the study
- Medical requirement for ranitidine use
- Current or past diagnosis of: porphyria, cancer, immune deficiency disorder
- Active infection at the time of screening
- Known liver, hematologic, renal disease
- Past history of allergic reaction to ranitidine or past history of hypersensitivity to any ingredient in the formulation or past history of hypersensitivity to other drugs
- Pregnant, planning to be pregnant, or breastfeeding during the study period
- Weight (kg) exceeds 109kg
Trial locations and contacts
1 site in 1 country.
About this study
The immune response against tumors can be highly effective in preventing tumor development, growth and metastasis under certain circumstances. However, tumor associated immune suppression can profoundly limit the impact of natural tumor immunity and also reduce the effectiveness of tumor immunotherapy strategies.
A major component of tumor associated immune suppression is mediated by myeloid cells, especially the monocytic subset of myeloid derived suppressor cells (MDSC). In recent studies that were conducted through a CCSRI Innovation grant, the investigators discovered that oral treatment of mice with the commonly used histamine receptor 2 (H2) antagonists ranitidine or famotidine inhibits both primary breast tumor development and metastasis, in three distinct mouse tumor models and reduces the numbers of monocytic MDSC. These findings have enormous potential to aid in effective cancer immunotherapy and may have immediate implications for cancer patients.
Read more
The objective of this investigation is to determine whether treatment with the H2 receptor antagonist ranitidine alters immune suppression, through modulation of immune cell populations.
The investigators will examine peripheral blood monocyte, neutrophil and NK cell numbers, subsets and activation status from healthy volunteers treated for 6 weeks with daily oral ranitidine.
Ranitidine is widely available and used over the counter in Canada. These drugs are widely recognized as safe, well tolerated and have very few side effects. It has been suggested that among the general population, over 10% of those over the age of 65 take such medications on a regular basis for relief against gastrointestinal discomfort. The outcome of pre-clinical studies in mice warrant further investigation into transferability to humans.
If the outcome of the current proposal proves to be viable, then these drugs could provide a safe method to reduce tumor associated immunosuppression with broad implications, both for current cancer patients and for those at high risk of developing cancer. Further to this, the outcome of our proposal may provide a new strategy for improving the effectiveness of T-cell mediated immunotherapy.
- Conditions
- Cancer
- Being tested
- Ranitidine
- Keywords
- Cancer, Immunity, Peripheral Blood Mononuclear Cells, Ranitidine
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RanitidineDrug
Also called Zantac
Thirty subjects will receive Ranitidine to a maximum of 900 mg/day in 2 daily oral doses for 6 weeks. The dosage target is 8 mg/kg/day, but the range of ranitidine intake will be between 7.5- 9 mg/kg/day. This is due to the formulation of the tablets, sold as 75, 150, and 300mg tablets.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Group | Experimental | This is a one arm study in which all individuals receive the treatment; therefore there is no allocation or randomization.
Thirty subjects will receive ranitidine to a maximum of 900 mg/day in 2 daily doses for 6 weeks. The dosage target is 8 mg/kg/day, but the range of ranitidine intake will be between 7.5- 9 mg/kg/day. This is due to the formulation of the tablets, sold as 75, 150, and 300mg tablets. The ranitidine will be taken orally. Receives: Drug: Ranitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intra-individual frequency and function of immune cell subsets
To determine the effect of histamine 2 receptor antagonists on immune cell function in healthy humans. Frequency and function of B cell, T cell, monocyte, NK cell and MDSC cells will be assessed by flow cytometry and ELISPOT.
Measured: Frequency and function were calculated as the values at 6 wks after treatment compared to the values at baseline.
Secondary outcomes (1)
Inter-individual frequency and function of immune cell subsets
To determine the effect of histamine 2 receptor antagonists on immune cell function cross-sectionally. B cell, T cell, monocyte, NK cell and MDSC cells will be assessed by flow cytometry and ELISPOT.
Measured: Frequency and function were calculated as the values at 6 wks after treatment compared to the values at baseline.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2017
- Study start1 May 2018
- Primary completion24 Oct 2018
- Study completion24 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CancerStudies of the same condition, open and under way.
- More trials run by Nova Scotia Health AuthorityThe 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 4
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Healthy individuals will be asked to take ranitidine for 6 weeks to determine the effect on peripheral blood immune cells.
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nova Scotia Health Authority
- Sponsor type
- University, hospital or other
- Collaborators
- Dalhousie University
- Responsible party
- Sponsor
- Investigators
- Lisa Barrett, MD/PhD, Principal investigator, Nova Scotia Health Authority
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03145012
- Sponsor's protocol ID
- SAIL-002
- Status last verified
- Feb 2023
- First submitted
- 26 Apr 2017
- Last updated
- 8 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: There is no plan to share the IPD with other researchers.
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Histamine Receptor 2 Antagonists as Enhancers of Anti-Tumour Immunity
- ClinicalTrials.gov ID
- NCT03145012
- Acronym / sponsor ID
- SAIL-002
- Conditions
- Cancer
- Keywords
- Cancer, Immunity, Peripheral Blood Mononuclear Cells, Ranitidine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Nova Scotia Health AuthorityUniversity, hospital or other
- Collaborators
- Dalhousie University
- Study start
- 1 May 2018 (actual)
- Primary completion
- 24 Oct 2018 (actual)
- Study completion
- 24 Oct 2018 (actual)
- First posted
- 9 May 2017 (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.
The immune response against tumors can be highly effective in preventing tumor development, growth and metastasis under certain circumstances. However, tumor associated immune suppression can profoundly limit the impact of natural tumor immunity and also reduce the effectiveness of tumor immunotherapy strategies.
A major component of tumor associated immune suppression is mediated by myeloid cells, especially the monocytic subset of myeloid derived suppressor cells (MDSC). In recent studies that were conducted through a CCSRI Innovation grant, the investigators discovered that oral treatment of mice with the commonly used histamine receptor 2 (H2) antagonists ranitidine or famotidine inhibits both primary breast tumor development and metastasis, in three distinct mouse tumor models and reduces the numbers of monocytic MDSC. These findings have enormous potential to aid in effective cancer immunotherapy and may have immediate implications for cancer patients.
The objective of this investigation is to determine whether treatment with the H2 receptor antagonist ranitidine alters immune suppression, through modulation of immune cell populations.
The investigators will examine peripheral blood monocyte, neutrophil and NK cell numbers, subsets and activation status from healthy volunteers treated for 6 weeks with daily oral ranitidine.
Ranitidine is widely available and used over the counter in Canada. These drugs are widely recognized as safe, well tolerated and have very few side effects. It has been suggested that among the general population, over 10% of those over the age of 65 take such medications on a regular basis for relief against gastrointestinal discomfort. The outcome of pre-clinical studies in mice warrant further investigation into transferability to humans.
If the outcome of the current proposal proves to be viable, then these drugs could provide a safe method to reduce tumor associated immunosuppression with broad implications, both for current cancer patients and for those at high risk of developing cancer. Further to this, the outcome of our proposal may provide a new strategy for improving the effectiveness of T-cell mediated immunotherapy.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Healthy individuals will be asked to take ranitidine for 6 weeks to determine the effect on peripheral blood immune cells.
| Arm | Type | Receives |
|---|---|---|
| Treatment Group | Experimental | Drug: RanitidineThis is a one arm study in which all individuals receive the treatment; therefore there is no allocation or randomization. Thirty subjects will receive ranitidine to a maximum of 900 mg/day in 2 daily doses for 6 weeks. The dosage target is 8 mg/kg/day, but the range of ranitidine intake will be between 7.5- 9 mg/kg/day. This is due to the formulation of the tablets, sold as 75, 150, and 300mg tablets. The ranitidine will be taken orally. |
Who may qualify
- Ages
- 20 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Age 20-50 years old, all sexes or genders
- Veins acceptable for blood draw
- Able to provide informed consent
- eGFR > 90 mL/min/1.73m2
- Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on physical examination and/or clinical laboratory evaluations (hematology, biochemistry, ECG, urinalysis). Clinical laboratory values within stated normal range; if not within this range, they must be without clinical significance
Key exclusion criteria (8 listed)
- Use of ranitidine for greater than 1 week within 6 months of starting the study
- Medical requirement for ranitidine use
- Current or past diagnosis of: porphyria, cancer, immune deficiency disorder
- Active infection at the time of screening
- Known liver, hematologic, renal disease
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 |
|---|---|---|
| RanitidineAlso: ZantacThirty subjects will receive Ranitidine to a maximum of 900 mg/day in 2 daily oral doses for 6 weeks. The dosage target is 8 mg/kg/day, but the range of ranitidine intake will be between 7.5- 9 mg/kg/day. This is due to the formulation of the tablets, sold as 75, 150, and 300mg tablets. | Drug | Treatment Group |
Primary outcome
Intra-individual frequency and function of immune cell subsets
Time frame: Frequency and function were calculated as the values at 6 wks after treatment compared to the values at baseline.
To determine the effect of histamine 2 receptor antagonists on immune cell function in healthy humans. Frequency and function of B cell, T cell, monocyte, NK cell and MDSC cells will be assessed by flow cytometry and ELISPOT.
1 secondary outcome
Inter-individual frequency and function of immune cell subsets
Time frame: Frequency and function were calculated as the values at 6 wks after treatment compared to the values at baseline.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2023.
- Individual participant dataSharing planned: No. There is no plan to share the IPD with other researchers.
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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.
Lisa Barrett, MD/PhD principal investigator
Nova Scotia Health Authority
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ranitidine in people with Cancer, run by Nova Scotia Health Authority at 1 site in Canada.
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 7 inclusion and 8 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: finished, as of the sponsor's last update on 8 Feb 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 Canada. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intra-individual frequency and function of immune cell subsets (time frame: Frequency and function were calculated as the values at 6 wks after treatment compared to the values at baseline.). 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 8 Feb 2023.