Immune system changes after thymectomy (removal of the thymus gland) and childhood cardiac (heart) transplant
| ISRCTN | ISRCTN10096625 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN10096625 |
| IRAS number | 298986 |
| Secondary identifying numbers | CPMS 51000, IRAS 298986 |
- Submission date
- 14/10/2022
- Registration date
- 17/10/2022
- Last edited
- 11/12/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Infections and Infestations
Plain English summary of protocol
Background and study aims
Post-transplant lymphoproliferative disease (PTLD) is a potentially fatal cancer seen in children who have received an organ transplant. In most children, PTLD is caused by Epstein-Barr Virus (EBV), which infects B-lymphocytes and is also known to cause glandular fever. These infected cells are normally kept under control by the immune system. However, the lifelong medication taken by transplant recipients to prevent organ rejection (immunosuppressants) also diminishes the control of this virus, leading to an abnormal accumulation of infected B-lymphocytes and their transformation into cancerous cells. PTLD affects approximately 1 in every 10 children within the first 5 years following heart transplant, representing a substantially higher risk than following other types of organ transplant. However, the reason for this increased risk is still poorly understood. We have previously identified that children with congenital heart disease are more likely to develop PTLD than children who develop an "acquired" heart disease. We believe this could be linked to their younger age at routine surgical removal of the thymus, a gland in the neck that is important for developing a healthy immune response to EBV.
The aim of this study is to collect clinical information and blood samples from children having a heart transplant to study their immune response to EBV.
Who can participate?
The study would like to recruit any child (0-18 years) who has a heart transplant in the UK. It will also recruit a small number of children having a kidney transplant as a comparison group.
What does the study involve?
Participating in the study involves reading an information sheet, asking questions and then agreeing to take part (consenting). Once part of the study, small additional blood samples will be taken prior to transplant, and during routine follow-up clinic appointments at 3, 6, 12 and 24 months after transplant. No extra appointments for blood tests are needed. The trial team will also collect information from the clinical records.
What are the possible benefits and risks of participating?
The study is intended to further our understanding of the causes of post-transplant lymphoproliferative disorders. Participants will not directly benefit but neither are there any identified risks.
Where is the study run from?
The study is run from the Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University (UK). It is being carried out in collaboration with Great Ormond Street Hospital as these two hospitals undertake all children's heart transplants in the UK.
When is the study starting and how long is it expected to run for?
January 2020 to December 2025
Who is funding the study?
The study is jointly funded by Cancer Research UK and The Lymphoma Research Trust (UK)
Who is the main contact?
Dr Simon Bomken, s.n.bomken@ncl.ac.uk
Contact information
Principal Investigator
Level 6, Herschel Building
Brewery Lane
Newcastle upon Tyne
NE1 7RU
United Kingdom
 ORCID ID |
0000-0001-9163-5738 |
|---|---|
| Phone | +44 1912082231 |
| s.n.bomken@ncl.ac.uk |
Study information
| Study design | Multicentre observational cohort study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cohort study |
| Study setting(s) | Hospital |
| Study type | Other |
| Participant information sheet | 42605 ITHACA study - PIS v2.5.2 (11 - 15 years) 07July2022.pdf |
| Scientific title | Immunology of thymectomy and childhood cardiac transplant cohort study |
| Study acronym | ITHACA |
| Study objectives | In children undergoing heart transplant, prior early thymectomy is associated with a dysregulated immune response to Epstein Barr virus infection. |
| Ethics approval(s) | Approved 11/112021, North of Scotland Research Ethics Service (Summerfield House, 2 Eday Road, Aberdeen, AB15 6RE, UK; +44 (0)1224558458; gram.nosres@nhs.scot), ref: 21/NS/0142. |
| Health condition(s) or problem(s) studied | Response to Epstein Barr virus (EBV) infection in children undergoing heart transplant |
| Intervention | Blood samples assessing EBV status and to investigate systemic immune parameters will be obtained pre-transplant and during two years following transplant. |
| Intervention type | Other |
| Primary outcome measure | 1. Innate and adaptive immune cell populations will be assessed in peripheral blood samples taken pre-transplant and at 3, 6, 12 and 24 months post-transplant. 2. Peri-transplant EBV-specific immune responses will be assessed in peripheral blood samples taken pre-transplant and at 3, 6, 12 and 24 months post-transplant. |
| Secondary outcome measures | There are no secondary outcome measures |
| Overall study start date | 01/01/2020 |
| Completion date | 31/12/2025 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 0 Years |
| Upper age limit | 18 Years |
| Sex | Both |
| Target number of participants | 40 |
| Key inclusion criteria | 1. Resident in the UK. 2. Aged 0 – 18 years. 3. Actively listed on the NHS Blood and Transplant (NHSBT) waiting list for a primary organ transplant OR awaiting transplant with a living related donor kidney OR recently transplanted with pre-transplant blood samples available. 4. Written informed consent. |
| Key exclusion criteria | 1. Has a pre-existing diagnosis of an inherited or acquired immunodeficiency. 2. Has an underlying thymic disorder. 3. Has previously received a bone marrow or organ transplant. 4. Has had a previous cancer diagnosis. 5. Withheld consent. 6. Weight under 2.5kg |
| Date of first enrolment | 31/03/2022 |
| Date of final enrolment | 30/06/2024 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Freeman Road
High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom
Newcastle upon Tyne
NE1 4LP
United Kingdom
London
WC1N 3JH
United Kingdom
Sponsor information
Hospital/treatment centre
Newcastle Joint Research Office
Regent Point
Regent Farm Road
Gosforth
Newcastle upon Tyne
NE3 3HD
England
United Kingdom
| Phone | +44 191 2825789 |
|---|---|
| aaron.jackson@nhs.net | |
| Website | http://www.newcastle-hospitals.org.uk/ |
"ROR" |
https://ror.org/05p40t847 |
Funders
Funder type
Charity
Private sector organisation / Other non-profit organizations
- Alternative name(s)
- CR_UK, Cancer Research UK - London, CRUK
- Location
- United Kingdom
No information available
Results and Publications
| Intention to publish date | 31/12/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Published as a supplement to the results publication |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The datasets generated and/or analysed during the current study will be published as a supplement to the subsequent results publication |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | 11-15 years version 2.5.2 |
07/07/2022 | 17/10/2022 | No | Yes |
| Participant information sheet | 16 years and above version 2.6.2 |
07/07/2022 | 17/10/2022 | No | Yes |
| Participant information sheet | 6-10 years version 2.6.1 |
02/12/2021 | 17/10/2022 | No | Yes |
| Participant information sheet | Parents version 2.5.2 |
07/07/2022 | 17/10/2022 | No | Yes |
| Protocol file | version 2.4 | 07/07/2022 | 17/10/2022 | No | No |
| HRA research summary | 28/06/2023 | No | No | ||
| Protocol article | 21/10/2023 | 23/10/2023 | Yes | No |
Additional files
- 42605 ITHACA study - Protocol v2.4 07July2022.pdf
- 42605 ITHACA study - PIS v2.6.1 (6 - 10 years) 02 dec2021.pdf
- 6-10 years
- 42605 ITHACA study - PIS v2.5.2 (Parents) 07July2022.pdf
- Parents
- 42605 ITHACA study - PIS v2.5.2 (11 - 15 years) 07July2022.pdf
- 11-15 years
- 42605 ITHACA study - PIS v2.6.2 (16 years and over) 07July2022.pdf
- 16 years and above
Editorial Notes
11/12/2023: The recruitment start date has been changed from 31/12/2023 to 30/06/2024.
23/10/2023: Publication reference added.
17/10/2022: Trial's existence confirmed by North of Scotland Research Ethics Service
