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Histamine Receptor 2 Antagonists as Enhancers of Anti-Tumour Immunity

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ClinicalTrials.gov Identifier: NCT03145012
Recruitment Status : Unknown
Verified March 2019 by Lisa Barrett, Nova Scotia Health Authority.
Recruitment status was:  Active, not recruiting
First Posted : May 9, 2017
Last Update Posted : March 11, 2019
Sponsor:
Collaborators:
Nova Scotia Health Authority
Dalhousie University
Information provided by (Responsible Party):
Lisa Barrett, Nova Scotia Health Authority

Tracking Information
First Submitted Date  ICMJE April 26, 2017
First Posted Date  ICMJE May 9, 2017
Last Update Posted Date March 11, 2019
Actual Study Start Date  ICMJE May 1, 2018
Estimated Primary Completion Date November 1, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 4, 2017)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 4, 2017)
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. ]
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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Histamine Receptor 2 Antagonists as Enhancers of Anti-Tumour Immunity
Official Title  ICMJE Histamine Receptor 2 Antagonists as Enhancers of Anti-Tumour Immunity
Brief 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.

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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention 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)
Primary Purpose: Basic Science
Condition  ICMJE Cancer
Intervention  ICMJE Drug: Ranitidine
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.
Other Name: Zantac
Study Arms  ICMJE Experimental: Treatment Group

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.

Intervention: Drug: Ranitidine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Actual Enrollment  ICMJE
 (submitted: May 4, 2017)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 1, 2019
Estimated Primary Completion Date November 1, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03145012
Other Study ID Numbers  ICMJE SAIL-002
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: There is no plan to share the IPD with other researchers.
Responsible Party Lisa Barrett, Nova Scotia Health Authority
Study Sponsor  ICMJE Lisa Barrett
Collaborators  ICMJE
  • Nova Scotia Health Authority
  • Dalhousie University
Investigators  ICMJE
Principal Investigator: Lisa Barrett, MD/PhD Nova Scotia Health Authority
PRS Account Nova Scotia Health Authority
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP