- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00949572
Measuring Responses to Sublingual Antigens
January 26, 2011 updated by: St George's, University of London
Characterisation of Human Disseminated Cellular and Humoral Immune Responses Following Sublingual or Intramuscular Deposition of Antigens
This study is a preliminary investigation of immune responses, in the blood and in cervical & vaginal secretions, to proteins ("antigens") taken up across the undersurface of the tongue.
Study Overview
Status
Completed
Conditions
Detailed Description
Animal studies have shown that this "sublingual" surface can take up antigens and stimulate immune responses, which may have a different character to responses induced by injecting the same antigens.
In previous studies of nasal and oral delivery, we used licensed vaccine preparations as pure and well-characterised model antigens safe for use in humans.
We will use a licensed "HPV" vaccine as the source of antigens in this study.
The quantity and character of responses (lymphocyte number and pattern of surface proteins, concentration and type of antibodies in fluids) will be measured in detail in various anatomical sites (blood, vaginal secretions) before and after delivery of antigens on three occasions.
As well as using established immune assays to characterise the responses, we will develop new research assays to detect populations of lymphocytes and antibodies present in secretions.
To ensure we have positive samples to include in our assays and validate new techniques, we will recruit some subjects to receive a standard intramuscular injection, as this is known to be nearly 100% reliable in inducing measurable immune responses.
As this is a preliminary study we will recruit enough subjects (based on our previous experience with nasal, oral and injected delivery) to ensure we generate sufficient responses we can measure.
We may be able to draw some tentative conclusions about differences in character of immune responses following sublingual or injected delivery, but it is not the intention of this initial study to formally compare these two routes.
If we observe that sublingual delivery in humans can induce immune responses, we can select assays to test any differences more formally in subsequent bigger and more focused studies.
Study Type
Interventional
Enrollment (Actual)
18
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
England
-
London, England, United Kingdom, SW17 0RE
- St George's Vaccine Institute, St George's University of London
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 35 years (ADULT)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
Female
Description
Inclusion Criteria:
- A female adult volunteer aged between 18 and 35 years old.
- Subjects who the investigator believes can and will comply with the requirements of the protocol.
- Provide written informed consent following a detailed written explanation of participation in the protocol.
- They are in good health as determined by medical history, physical examination, haematology testing, and clinical judgement before entering into the study.
- They are available for the whole duration of the study.
- If of childbearing potential, must have a negative pregnancy test before each immunisation.
- They have not donated blood during 3 months prior to study entry and agree to not donate for 3 months after the end of their participation in the study.
- They are eligible for free medical treatment
Exclusion Criteria:
- They have already been vaccinated with an HPV vaccine
- They have participated in a clinical trial in the last 6 months in which they have been exposed to an investigational product (pharmaceutical product or placebo or device) or concurrent participation in another clinical research study at the time of enrolment.
- Use of any investigational or non-registered product (drug or vaccine) within 30 days preceding the first dose of challenge agent, or planned use during the study period.
- They are pregnant or breast-feeding.
- They have a known or suspected ongoing cervico-vaginal disease, malignancy or abnormality discovered at time of screening.
- They present in the samples obtained at the screening visit: positive results for HIV, HBs Ag, anti-HBc and anti-HCV antibody, a clinically significant abnormality in haematology. Normal ranges will be defined by the pathology laboratory undertaking assays.
- They have a clinically significant acute or chronic pulmonary, cardiovascular, hepatic or renal functional abnormality, blood or neurological disorders, immune dysfunction, autoimmune diseases, diabetes (excluding history of gestational diabetes), or malignancy at the time of enrolment, as determined by medical history, physical examination or laboratory screening tests.
- They have received any form of immunosuppressive therapy in the past 6 months.
- They are receiving any medications via vaginal route (as this may interfere with collection of samples).
- They have any tongue or frenulum piercings or oral jewellery that may interfere with sublingual delivery.
- They have received blood products or immunoglobulins 120 days prior to enrolment.
- They have thrombocytopaenia or any coagulation disorder (because bleeding may occur following an intramuscular administration in these individuals).
- Any other medical, psychiatric or social condition, drug treatment, occupational or other responsibility that, in the judgement of the investigator, would interfere with or serve as a contradiction to adherence to the study protocol or ability to give informed consent.
- Individuals who cannot read or speak fluent English.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: BASIC_SCIENCE
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Intramuscular administration
Intramuscular injection of HPV vaccine proteins
|
1 intramuscular dose (0.5 ml) on month 0, 1 and 4 containing approximately: Human Papillomavirus Type 6 L1 protein 20 micrograms Human Papillomavirus Type 11 L1 protein 40 micrograms Human Papillomavirus Type 16 L1 protein 40 micrograms Human Papillomavirus Type 18 L1 protein 20 micrograms
Other Names:
1 sublingual application on month 0, 1 and 4 of 0.5 ml containing approximately: Human Papillomavirus Type 6 L1 protein 20 micrograms Human Papillomavirus Type 11 L1 protein 40 micrograms Human Papillomavirus Type 16 L1 protein 40 micrograms Human Papillomavirus Type 18 L1 protein 20 micrograms
Other Names:
|
EXPERIMENTAL: Sublingual administration
Sublingual administration of HPV vaccine proteins
|
1 intramuscular dose (0.5 ml) on month 0, 1 and 4 containing approximately: Human Papillomavirus Type 6 L1 protein 20 micrograms Human Papillomavirus Type 11 L1 protein 40 micrograms Human Papillomavirus Type 16 L1 protein 40 micrograms Human Papillomavirus Type 18 L1 protein 20 micrograms
Other Names:
1 sublingual application on month 0, 1 and 4 of 0.5 ml containing approximately: Human Papillomavirus Type 6 L1 protein 20 micrograms Human Papillomavirus Type 11 L1 protein 40 micrograms Human Papillomavirus Type 16 L1 protein 40 micrograms Human Papillomavirus Type 18 L1 protein 20 micrograms
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Concentration and isotype profile of antigen-specific antibody in cervico-vaginal secretions measured by ELISA and/or LUMINEX assay
Time Frame: 0, 1, 4 and 5 months after first immunization
|
0, 1, 4 and 5 months after first immunization
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Concentration and isotype profile of antigen-specific antibody in serum measured by ELISA and/or LUMINEX assay
Time Frame: 0, 1, 4 & 5 months after first immunization
|
0, 1, 4 & 5 months after first immunization
|
Frequency and isotype profile of antigen-specific antibody secreting cells in blood
Time Frame: 0 and 1 week after each immunization
|
0 and 1 week after each immunization
|
Frequency and expression profile of mucosa-associated homing, memory and regulatory markers on antigen-specific T cells in blood in response to in vitro antigen stimulation
Time Frame: 0 and 4 weeks after each immunization
|
0 and 4 weeks after each immunization
|
Profile of cytokine secretion by peripheral blood mononuclear cells in response to in vitro antigen stimulation measured by ELISA
Time Frame: 0 and 4 weeks after each immunization
|
0 and 4 weeks after each immunization
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: David JM Lewis, MD, St George's, University of London
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
September 1, 2009
Primary Completion (ACTUAL)
June 1, 2010
Study Completion (ACTUAL)
January 1, 2011
Study Registration Dates
First Submitted
July 29, 2009
First Submitted That Met QC Criteria
July 29, 2009
First Posted (ESTIMATE)
July 30, 2009
Study Record Updates
Last Update Posted (ESTIMATE)
January 27, 2011
Last Update Submitted That Met QC Criteria
January 26, 2011
Last Verified
January 1, 2010
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- SG09-EN01
- REC number: 09/80803/77 (OTHER: NRES, UK)
- EC grant number 201038 (OTHER: European Commission)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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