A study of cell signalling biomarkers in patients with tuberous sclerosis
| ISRCTN | ISRCTN62388748 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN62388748 |
| IRAS number | 316411 |
| Secondary identifying numbers | mTOR Bio-001, IRAS 316411, CPMS 52900 |
- Submission date
- 31/08/2022
- Registration date
- 09/09/2022
- Last edited
- 02/01/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Genetic Diseases
Plain English summary of protocol
Background and study aims?
Tuberous sclerosis is a rare genetic condition that causes mainly non-cancerous tumours to develop in different parts of the body. It is thought that a biochemical pathway known as the mTOR (mechanistic Target of Rapamycin) pathway is overactive in tuberous sclerosis. Specific chemicals found naturally in the blood are linked to this pathway. These naturally occurring chemicals are called biomarkers. These chemicals could show how well the body responds to new treatments and in turn speed up the discovery of new medicines. This study will check that the method by which the biomarkers are being measured is working and appropriate for patients with tuberous sclerosis.
Who can participate?
Patients aged from 10 to 65 years known to have tuberous sclerosis
What does the study involve?
This study requires the patient to provide a blood sample to measure mTOR biomarkers in their blood. No additional medication will be received, and all other treatments for tuberous sclerosis will remain as they are. Wherever possible the study will be conducted as part of usual clinic visits. The first visit is a screening visit so that the doctor can check the patient is suitable to take part, provide the study information and if appropriate, take consent. This will take about 60 minutes. The second visit (up to 6 weeks later) will be to check there are no changes in health status/medications and to take the blood sample. This will take about 30 minutes. To provide this sample, the patient must not eat for 8 hours beforehand (overnight) and avoid drinks containing sugar and alcohol. Then a qualified healthcare professional (nurse, doctor or phlebotomist) will take 10 ml (about 2 teaspoons) of blood. It is intended that extra blood will be taken as part of routine blood tests. Blood will then be transferred, on the same day, to a central laboratory that will analyse your blood sample for the mTOR biomarkers.
What are the possible benefits/risks of participating?
Research like this helps to continually improve the treatments and care provided to all patients. Although no extra benefit is received from taking part in this study the results will be used to support the use of biomarkers in future clinical studies which means it could help in the development of new drugs. The patient's routine treatment remains unchanged. The risk involved in taking blood is the same as for any clinic visit where blood is taken. At the site where blood is taken there may have pain or bruising and, although extremely rare, an infection could develop. The patient may feel dizzy or could faint during or after blood has been taken.
Where is the study run from?
1. Bristol Childrens Hospital (UK)
2. The Royal Sussex County Hospital (UK)
3. St George’s Hospital Medical School (UK)
When is the study starting and how long is it expected to run for?
January 2022 to February 2023
Who is funding the study?
Aeovian Pharmaceuticals Inc. (USA)
Who is the main contact?
1. Dr Sam Amin, sam.amin@uhbw.nhs.uk
2. Kaye Hallett, khallett@aeovian.com
3. Pierre Rehbaum, pierre.rehbaum@iqvia.com
Contact information
Public
7, Oriel Hill
Camberley
GU15 2JW
United Kingdom
| Phone | +44 (0)7786117003 |
|---|---|
| khallett@aeovian.com |
Principal Investigator
University Hospitals Bristol and Weston
Marlborough St
Bristol
BS1 3NU
United Kingdom
| Phone | +44 (0)7886660762 |
|---|---|
| sam.amin@uhbw.nhs.uk |
Scientific
Aeovian Pharmaceuticals Inc
2930 Domingo Dr
Suite 145
Berkeley
CA 94705
United States of America
| Phone | +1 (0)510 439 1050 |
|---|---|
| dryman@aeovian.com |
Study information
| Study design | Non-interventional study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Biomarker study |
| Study setting(s) | Hospital |
| Study type | Other |
| Participant information sheet | Not available in web format |
| Scientific title | A study to validate the assay of biomarkers of the mTOR signalling pathway (p-S6RP(Ser240/244) for mTORC1 and p-AKT (Ser473) for mTORC2) and other non-genetic biomarkers in whole blood samples from patients with tuberous sclerosis complex (TSC): Biomarkers in Patients with Tuberous Sclerosis (BioPaTS) |
| Study acronym | BioPaTS |
| Study objectives | It is thought that a biochemical pathway known as the mTOR (mechanistic Target of Rapamycin) pathway is overactive in tuberous sclerosis. Specific chemicals found naturally in the blood are linked to this pathway. These naturally occurring chemicals are called biomarkers. These chemicals could show how well the body responds to new treatments and in turn speed up the discovery of new medicines. This study will check that the method by which the biomarkers are being measured is working and appropriate for patients with tuberous sclerosis. |
| Ethics approval(s) | Approved 22/7/2022, South Central – Hampshire A Research Ethics Committee (Temple Quay House, 2 The Square, Bristol Research Ethics Committee Centre, BS1 6PN, UK; +44 (0)207 104 8196; hampshirea.rec@hra.nhs.uk), ref: 22/SC/0188 |
| Health condition(s) or problem(s) studied | Tuberous sclerosis complex (TSC) |
| Intervention | This study requires the patient to provide a blood sample to measure mTOR biomarkers in their blood. No additional medication will be received, and all other treatments for tuberous sclerosis will remain as they are. Wherever possible the study will be conducted as part of usual clinic visits. The first visit is a screening visit so that the doctor can check the patient is suitable to take part, provide the study information and if appropriate, take consent. This will take about 60 minutes. The second visit (up to 6 weeks later) will be to check there are no changes in health status/medications and to take the blood sample. This will take about 30 minutes. To provide this sample, the patient must not eat for 8 hours beforehand (overnight) and avoid drinks containing sugar and alcohol. Then a qualified healthcare professional (nurse, doctor or phlebotomist) will take 10 ml (about 2 teaspoons) of blood. It is intended that extra blood will be taken as part of routine blood tests. Blood will then be transferred, on the same day, to a central laboratory that will analyse the blood sample for the mTOR biomarkers. |
| Intervention type | Other |
| Primary outcome measure | Inter- and intra- assay precision measured as % inhibition of the mTOR signal, as measured by electrochemiluminescence (ECL) units at a single timepoint |
| Secondary outcome measures | The stability of signal in samples after freeze/thawing cycles and long-term storage (up to 1 month), pre- and post-processing of blood will be assessed by measuring ECL signal strength and % inhibition at a single timepoint |
| Overall study start date | 25/01/2022 |
| Completion date | 28/02/2023 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Sex | Both |
| Target number of participants | 12 evaluable blood samples |
| Total final enrolment | 14 |
| Key inclusion criteria | 1. Patients who are able to provide written informed consent appropriate to age/local law - patient and/or parent(s)/legal representative who are willing and able to give informed consent/assent for participation in the study 2. Patients who have a definite diagnosis of tuberous sclerosis complex (TSC) according to the Updated International Tuberous Sclerosis Complex Diagnostic Criteria (Paediatric Neurology 123 (2021) 3. Patients who are male or female aged 10 to 65 years 4. All medications or interventions for epilepsy (including ketogenic diet and any neurostimulation devices for epilepsy) must have been stable for 4 weeks prior to the screening visit |
| Key exclusion criteria | 1. Patients with a history of pseudo-seizures 2. Patients with clinically significant unstable medical conditions other than epilepsy 3. Patients who have a serious intercurrent illness or uncontrolled disease that could compromise the interpretation of the data from this study 4. Patients who have received treatment with felbamate, unless continuous for >1 year 5. Patients who have received any other investigational product within the 30 days prior to the screening visit 6. Patients who are unlikely to comply with the requirements of this study |
| Date of first enrolment | 05/09/2022 |
| Date of final enrolment | 13/02/2023 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Bristol
BS2 8BJ
United Kingdom
BN2 5BE
United Kingdom
SW17 0RE
United Kingdom
Sponsor information
Industry
2930 Domingo Ave., Suite #145
Berkeley
94705
United States of America
| Phone | +1 (0)510 439 1050 |
|---|---|
| ahulme@aeovian.com | |
| Website | https://www.aeovian.com/ |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 30/12/2023 |
|---|---|
| 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 peer-reviewed journal |
| IPD sharing plan | All data generated or analysed during this study will be included in the subsequent results publication |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
02/01/2024: Contact details updated.
09/02/2023: The following changes were made to the trial record:
1. The recruitment end date was changed from 19/12/2022 to 13/02/2023.
2. The overall end date was changed from 31/01/2022 to 28/02/2023.
3. The plain English summary was updated to reflect these changes.
4. The contact was updated
01/11/2022: The following changes were made to the trial record:
1. The recruitment end date was changed from 28/10/2022 to 19/12/2022.
2. The overall end date was changed from 16/12/2022 to 31/01/2022.
3. The participant level data sharing plan was added.
03/10/2022: Internal review.
07/09/2022: Trial's existence confirmed by the HRA.
