Understanding the impact of treatments for inflammatory bowel disease on immune responses to SARS-CoV2 vaccination
| ISRCTN | ISRCTN13495664 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13495664 |
| IRAS number | 292123 |
| Secondary identifying numbers | IRAS 293123 |
- Submission date
- 26/10/2021
- Registration date
- 13/12/2021
- Last edited
- 21/01/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Other
Plain English summary of protocol
Background and study aims
Vaccination is likely to be a key weapon to protect the health of the world’s population from COVID19 and is likely to be especially important in high risk individuals, such as those with pre-existing conditions including Inflammatory bowel disease (IBD).
Many IBD patients take immunosuppressive drugs, which leaves them vulnerable to infection. However, the risks associated with immunosuppression are not limited to increased susceptibility to infection. Immunosuppressive drugs may reduce the effectiveness of some vaccines, which could have major implications for the safety of immunosuppressed patients in the COVID-19 era.
The ultimate purpose of this study is to determine whether patients on different immunosuppressive drugs have impaired immune responses to SARS-CoV-2 vaccination. We will also investigate important mechanisms of successful vaccination and identify predictors of vaccination failure. This information will help planning for treatment and vaccination of immunosuppressed patients in the future.
Who can participate?
Patients with or without IBD who are on immunosuppressive medication and are receiving vaccination against SARS-CoV2
What does the study involve?
VIP is a prospective observational study to be conducted in IBD patients undergoing vaccination against SARS-CoV-2 at multiple centres across the United Kingdom. 600 IBD patients on different IBD medication (immunomodulators, anti-TNFs, combination immunomodulator and anti-TNF, Vedolizumab, Ustekinumab and Tofacitinib), and 200 healthy participants will be recruited. We will measure antibody levels and how the immune system responds to the vaccine over time. We will follow participants over two study visits at 60 days after the second dose of vaccine and 35-42 days after the third dose of vaccine.
What are the possible benefits and risks of participating?
The information we get from this study might help us to improve vaccination for patients on immunosuppressive treatments in the future. The findings may also help to inform government policies such as shielding for immunosuppressed patients. Travel costs for attending the research centre will be covered, a maximum of £20 per research visit will be offered. No significant risks to participants are anticipated. There may be bruising and discomfort at the site of the blood test, as with any blood test. The amount of blood you will donate is small enough that it should not make you feel faint or cause a low blood count.
Where is the study run from?
Imperial College London (UK)
When is the study starting and how long is it expected to run for?
March 2021 to June 2022
Who is funding the study?
Pfizer (USA)
Who is the main contact?
Dr James Alexander, j.alexander@imperial.ac.uk
Contact information
Public
10th floor Commonwealth Building Hammersmith Campus
Du Cane Road
London
W12 0HS
United Kingdom
 ORCID ID |
0000-0001-8542-327X |
|---|---|
| Phone | +44 (0)20 7589 5111 |
| j.alexander@imperial.ac.uk |
Study information
| Study design | Prospective observational clinical study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Longitudinal study |
| Study setting(s) | Hospital |
| Study type | Other |
| Participant information sheet | https://www.vipstudy.uk/info |
| Scientific title | SARS-CoV2 Vaccination immunogenicity in Immunosuppressed inflammatory bowel disease Patients |
| Study acronym | VIP |
| Study objectives | • Concentrations of anti-SARS-CoV2 antibodies following vaccination will be reduced in IBD patients prescribed anti-TNF therapy and other immunosuppressive agents. • The durability of antibodies against SARS-CoV2 following vaccination will be reduced in IBD patients prescribed anti-TNF therapy and other immunosuppressive agents. • SARS-CoV2 antigen-specific T-cell responses following vaccination will be reduced in IBD patients prescribed anti-TNF therapy anti-TNF therapy and other immunosuppressive agents. |
| Ethics approval(s) | Approved 18/03/2021, Wales Research Ethics Committee 5 (Health and Care Research Wales, Castlebridge 4,15-19 Cowbridge Road East, Cardiff, CF11 9AB, UK; +44 (0)1874 615950 Wales.REC5@wales.nhs.uk), ref 21/WA/0105 |
| Health condition(s) or problem(s) studied | Immune responses to SARS-CoV-2 vaccination in immunosuppressed inflammatory bowel disease patients. |
| Intervention | 600 IBD patients will be recruited stratified according to the immunosuppressive medication they are on. Patients must have been for at least 3 months on the following treatments: thiopurines (n=100), infliximab (anti-TNF) (n=100), combination infliximab/thiopurines (n=100), vedolizumab (n=100), ustekinumab (n=100) and tofacitinib (n=100). 200 healthy people without IBD will also be recruited. Following pre-screening, participants will be consented and enrolled in the study. Details including IBD phenotype, patient demographics and disease activity will be collected via the patient questionnaires, which will be completed after study consent is given. 40mL blood draw will be sampled at 2 time points, after 2nd dose of vaccination (days 60- 85), and 35-42 days post third dose of vaccine, to assess serology and T-cell responses. |
| Intervention type | Biological/Vaccine |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Not provided at time of registration |
| Primary outcome measure | Immunogenicity to routinely administered SARS-CoV2 vaccination at day 60-85 post second dose of vaccination, measured as the geometric mean titre of Anti-SARS-CoV-2 spike (S) antibodies (Roche Elecsys immunoassay)in IBD patients on immunosuppressive treatment regimens compared to non-IBD control participants. |
| Secondary outcome measures | 1. Immunogenicity to vaccination at the first visit (between days 60- 85) post second dose of vaccination, measured as the geometric mean titres of S1 binding IgG and RBD IgG antibodies in IBD patients on immunosuppressive treatment regimens compared to non-IBD control participants. 2. Immunogenicity to a third dose (or booster dose) of vaccination at the second visit, 35-42 days (+/- 7 days) following the third dose, measured as the geometric mean titres of neutralising anti-SARS-CoV2 antibodies, S1-binding IgG antibodies and RBD IgG antibodies in IBD patients. 3. Proportion of IBD patients on immunosuppressive treatment regimens compared to non-IBD control participants with seroprotection against SARS-CoV2 at the first visit (between days 60- 85) and at the second visit (35-42 days following third dose of vaccine). 4. Adaptive immune response to vaccination measured using T cell assays and longitudinal transcriptomics in each study arm. |
| Overall study start date | 18/03/2021 |
| Completion date | 01/06/2022 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 600-800 |
| Total final enrolment | 483 |
| Key inclusion criteria | 1. Adults (aged ≥18 years) 2. Established diagnosis of CD or UC using standard definitions of IBD or healthy people without IBD. 3. Established on current immunosuppressive regimen (as listed in ‘study subjects’ section) for at least 12 weeks. This criteria does not apply to healthy participants without IBD. 4. Receiving vaccination against SARS-CoV2 5. Able to give informed consent. |
| Key exclusion criteria | 1. Unable to give informed consent 2. Patients <18 years of age 3. Recipients of ‘accelerated dosing’ of vaccination (I.e. second dose of SARS-CoV-2 vaccination given within 42 days of first dose). 4. Patients on any other immune suppressants to those listed in study subjects section (other than oral steroids). 5. Excluded medication includes: 5.1. adalimumab 5.2. golimumab 5.3. certolizumab 5.4. mesazaline 5.5. mycophenolate 5.6. tacrolimus 5.7. thalidomide 5.8. ciclosporin 5.9. cyclophosphamide 5.10. hydroxychloroquine 5.11. leflunomide 5.12. methotrexate 5.13. mycophenolate 5.14. sulfasalazine |
| Date of first enrolment | 28/05/2021 |
| Date of final enrolment | 01/01/2022 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
Study participating centres
Du Cane Road
London
W12 0HS
United Kingdom
Edinburgh
EH4 2XU
United Kingdom
EX2 5DW
United Kingdom
Cambridge
CB2 0QQ
United Kingdom
Harrow
HA1 3UJ
United Kingdom
Whitechapel
London
E1 1BB
United Kingdom
Sponsor information
University/education
Joint Research Compliance Office
Imperial College London and Imperial College Healthcare NHS Trust
Room 215, Level 2, Medical School Building
Norfolk Place
London
W2 1PG
England
United Kingdom
| Phone | +44 (0)207 594 9459 |
|---|---|
| becky.ward@imperial.ac.uk | |
| Website | https://www.imperial.ac.uk/joint-research-compliance-office |
"ROR" |
https://ror.org/041kmwe10 |
Funders
Funder type
Industry
Government organisation / For-profit companies (industry)
- Alternative name(s)
- Pfizer Inc., Pfizer Consumer Healthcare, Davis, Charles Pfizer & Company, Warner-Lambert, King Pharmaceuticals, Wyeth Pharmaceuticals, Seagen
- Location
- United States of America
Results and Publications
| Intention to publish date | 01/12/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | Individual participant deidentified data that underlie the results reported in this study will be available immediately after publication for a period of 5 years. The data will be made available to investigators whose proposed use of the data has been approved by an independent review committee. Analyses will be restricted to the aims in the approved proposal. j.alexander@imperial.ac.uk |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 1.7 | 12/10/2021 | 27/10/2021 | No | No |
| Interim results article | 03/02/2022 | 07/02/2022 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Results article | 01/04/2022 | 18/07/2023 | Yes | No | |
| Results article | 01/11/2022 | 18/07/2023 | Yes | No | |
| Results article | 01/02/2023 | 18/07/2023 | Yes | No | |
| Results article | 05/10/2023 | 16/10/2023 | Yes | No | |
| Results article | 23/04/2024 | 21/01/2025 | Yes | No |
Additional files
Editorial Notes
21/01/2025: Publication reference added.
16/10/2023: Publication reference added.
18/07/2023: The following changes were made to the trial record:
1. Publication references added.
2. The total final enrolment was added.
07/02/2022: Publication reference added.
27/10/2021: Trial's existence confirmed by NHS HRA.
