Ignite Creation Date:
2024-07-17 @ 11:44 AM
Last Modification Date:
2024-10-26 @ 3:33 PM
Study NCT ID:
NCT06478121
Status:
RECRUITING
Last Update Posted:
2024-06-27
First Post:
2024-06-11
Brief Title:
Understanding Beta Cell Disorders Through the Study of Rare Genotypes ENDURE
Sponsor:
University of Exeter
Organization:
University of Exeter
Study Overview
Official Title:
Understanding Beta Cell Disorders Through the Study of Rare Genotypes ENDURE
Status:
RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ENDURE
Brief Summary:
This observational recruit by genotype study aims to provide insights into the cellular and molecular pathways underlying beta cell disorders and their physiological consequences Eligible individuals are those with and without a pathogenic genetic variant acting as case and control respectively Using a recruit by genotype approach the researchers will perform detailed and specific analysis according to the individuals genetic variant
The studys main aims are to 1 identify and describe biomarkers and cellular features in blood samples that occur because of the rare causal genetic variant 2 study the altered physiology or cellular function that are due to the rare causal genetic variant
Participants will attend a study visit that will entail
Consent
Data collection
Height and weight measures
Blood samples
MRI optional dependent on genotype and sub-study objectives
There is no treatment and the participants normal clinical care will be unaffected and will continue uninterrupted
A small subset of participants may be invited for further sub-studies in the future Researchers may recruit sex-matched healthy controls without the variant of interest with similar age and BMI age -15 BMI - 3 kgm2 for specified case-control studies
The studys main aims are to 1 identify and describe biomarkers and cellular features in blood samples that occur because of the rare causal genetic variant 2 study the altered physiology or cellular function that are due to the rare causal genetic variant
Participants will attend a study visit that will entail
Consent
Data collection
Height and weight measures
Blood samples
MRI optional dependent on genotype and sub-study objectives
There is no treatment and the participants normal clinical care will be unaffected and will continue uninterrupted
A small subset of participants may be invited for further sub-studies in the future Researchers may recruit sex-matched healthy controls without the variant of interest with similar age and BMI age -15 BMI - 3 kgm2 for specified case-control studies
Detailed Description:
The human body needs sugar for energy but too much or too little sugar in the blood is bad for health To control the amount of sugar in the blood a molecule called insulin is made by specialised beta cells in the pancreas In diabetes beta cells dont make enough insulin which causes high blood sugar levels In hyperinsulinism they make too much insulin leading to very low blood sugar levels Over time these disorders can lead to serious health problems
The cause of some cases of diabetes and nearly all cases of hyperinsulinism is a single spelling mistake in the persons DNA a variant that changes how the insulin producing beta cells work
The overarching aim of the ENDURE study is to understand how DNA variants cause beta cell disorders and to improve understanding of how beta cells work It is hoped that the insights from this research may lead to new ways to treat andor improve the lives of people living with beta cell disorders
Participants will be selected based on having a confirmed disease-causing genetic change that results in beta cells not working properly or a suitably matched control same sex close in age and weight
Consent Prospective study participants will be provided with the appropriate participant information sheet PIS and Sub-Study Flowchart detailing the study and procedures specific to the participants genotype If interested in participating the ENDURE study team will contact them to discuss the study in detail and answer any questions and address concerns raised to allow the prospective participant to make an informed decision regarding taking part in the study For the Imaging Sub-Study following receipt of verbal consent participants will be asked to complete a MRI Safety Checklist Screening Form that is necessary to screen them prior to booking their MRI scan Prospective study participants are individuals with a rare genetic mutation that is associated with a monogenic beta cell disorder The cohort of prospective study participants is diverse in terms of background primary language home country To have an inclusive study set-up the study team will provide documents that are translated into the participants or guardians primary language where English is not the primary language Additionally a National Health Service NHS appointed interpreterinterpretation service eg Language Line will be arranged for phone calls and the study visit to ensure clear communication The participants clinician may also attend and provide translation
Withdrawal of consent All participants and their legal guardians will be informed of their right to withdraw from the study without stating a reason at any time up to and including data and sample analysis without prejudice or jeopardy to any future clinical care If a participant permanently withdraws from the study the reason if provided will be recorded
Research visits All study participants will be invited to the National Institute for Health and Care Research NIHR Exeter Clinical Research Facility Exeter CRF or alternative convenient location to provide written informed consentassent and undergo Core Study data collection measurements and provide blood samples collected by a nurse or doctor paediatric if necessary fully trained in this procedure This Core Study visit should take approximately 40 minutes to 1 hour
MRI Depending on their genotype participants will be invited to take part in the Imaging Sub-Study to have an MRI Magnetic Resonance Imaging scan to measure organ size and body fat distribution The MRI appointment may be arranged as a separate visit if more convenient for the participant
Patients with genetic variants that result in neonatal diabetes often lack insulin in utero as well as after birth These patients are typically born at proximately half normal birth weight as the foetus in the womb lack insulin and this is a major growth factor for the foetus To allow assessment of the impact of lack of insulin in utero on post-natal growth fat distribution and the pancreatic size participants with genetic subtypes that stop insulin secretion in utero will be invited to have an MRI optional during their visit A CE marked MRI scanner at the Mirielle Gillings Neuroimaging Centre MGNC will be used to acquire multiple standard vendor sequences of the participants body to look at fat distribution and measure organ size 40-60 minutes During the procedure the participant can ask to stop the procedure at any time between and during scans and can also have breaks between the scans A priority scan list will be followed to obtain images according to importance to address the research questions
Data Collection and Recording All participants will be pseudo-anonymised by assigning a unique study identifier ID under which all data and samples collected will be recorded and stored The relevant visit Case Report Form CRF will capture all the information required to ensure that all the documented statistical information dictated in the protocol is captured and documented at each visit This also serves to monitor patient eligibility and safety at Sponsor level Hard copies will be stored in the Trial Master File TMF
Sample collection and storage All samples will be collected and processed by a suitably qualified and trained member of the clinicalresearch team whose role is documented on the study delegation log The amount of blood to be drawn from participants is solely for research purposes and will not exceed the recommended limits in accordance with World Health Organization WHO guidelines according to age andor weight of study participants Children will be offered use of a topical anaesthetic as is common practise during phlebotomy of children Blood collection will be made into specific blood collection tubes according to the study aim
The Exeter Blood Sciences Laboratory will provide analyses from routine biochemistry tests available in the NHS test repertoire All assays are CE marked fully validated and accredited by Clinical Pathology Accreditation CPA Clinical results will be available within 21 days of receipt of the sample
The investigators laboratories based at the University of Exeter will receive blood samples to isolate blood fractions according to established protocols according to manufacturers description A detailed Standard Operating Procedure SOP will be provided detailing clear instruction to the logistics of sample labelling logging and management of sample processing and storage of isolated blood fractions
Robust procedures in compliance with the Human Tissue Act 2004 are always followed to monitor and maintain the integrity and traceability of the samples stored in a licensed area including their disposal All samples will be processed logged and frozen using sample-appropriate storage procedures Human Tissue Authority HTA approved locations for storage are available within the investigators laboratories at the University of Exeter Medical School All saved samples will be stored under the study ID with the file linking the study code to personal identifiable information held securely by the PI accessible only to personnel with training in data protection who require this information to perform their duties Those with access to personal identifiable data will be documented on the study Delegation Log
The Study ID will provide a robust pseudo-anonymised system for management and location tracking of all study samples The research team will monitor consent status via the study database Where samples are unable to be collected this should be documented under the participant Study ID with reason for non-collection provided
Transfer of custodianship of stored samples with consent to the Genetic Beta Cell Research Bank GBCRB managed by The Royal Devon University Healthcare NHS Foundation Trusts Exeter Genomics Laboratory may occur during the study or at the end of the study as defined above Stored samples will then be made available for further separate ethically-approved research
End of Study The parameter marking the end of the study is the 3 months after the final participants final visit or 3 months prior to end of the funded period whichever is later to allow for final collection of data and analysis
Incidental Findings Investigations in this study are aimed to answer research questions and not guide clinical care Therefore individual results will not be reported routinely to the participant and their clinicians However incidental findings outside the range of the normal population may occur All incidental findings will be discussed with the Chief Investigator CI or medically qualified delegate to assess whether immediate clinical action is required If required the test results would be communicated back to the participant and their healthcare providers to enable initiation of follow-up andor treatment Participants will not expect to receive individual results unless clinical action is needed A statement to this effect is included in the information sheet and consent form
Safety The timeframe for recording a Serious Adverse Event SAE will be from the time of consent to one week following the last visit of a study participant Any reportable adverse effects noted will be reported within 24 hours to the CI and the Sponsor as per standard NHS RD protocols Nominated co-investigators will be authorised to sign the SAE forms in the absence of the CI at the co-ordinating site or the PI at the participating sites
Indemnity The lead Sponsor University of Exeter provides cover under its No Fault Compensation Insurance which provides for payment of damages or compensation in respect of any claim made by a research participant for bodily injury arising out of participation in a clinical trial or healthy volunteer study with certain restrictions Public liability insurance is provided to cover the design and management of the study
NHS indemnity covers potential legal liability i for harm to participants arising from the design of the research and ii of investigatorsresearch staff for harm to participants arising from the conduct of the research
Access to Final Study Dataset and Archiving Where consent is given by the participantparentguardian their remaining samples and data from the project will be gifted to the Genetic Beta Cell Research Bank GBCRB an approved tissue bank REC ref Wales Research Ethics Committee 5 22WA0268 in Exeter to be used for future research The GBCRB is managed by The Royal Devon University Healthcare NHS Foundation Trusts Exeter Genomics Laboratory Access to samplesdata is through application to the Genetic Beta Cell Research Bank steering committee
When the research study is complete it is a requirement of the UK Policy Framework for Health Social Care and Sponsor Trust Policy that the records are kept for a further 15 years At the end of the study the study data will be archived by the CI at the University of Exeter
Dissemination Policy Results will be written up and submitted for publication in open-access peer-reviewed journals and prior to open access preprint servers eg such as medRxiv or bioRxiv Abstracts will be submitted to national and international conferences Results will also be presented to colleagues clinical and research at regular in-house meetings Ongoing updates on study progress will also be made to Exeter PPIE group for continued feedback
Some data will also be deposited in electronic archives that are available to other researchers upon request to ensure data is used only to advance scientific and medical understanding
Written information outlining the key findings of the study will be sent to all participants and uploaded to the NIHR Exeter CRF and study websites
The cause of some cases of diabetes and nearly all cases of hyperinsulinism is a single spelling mistake in the persons DNA a variant that changes how the insulin producing beta cells work
The overarching aim of the ENDURE study is to understand how DNA variants cause beta cell disorders and to improve understanding of how beta cells work It is hoped that the insights from this research may lead to new ways to treat andor improve the lives of people living with beta cell disorders
Participants will be selected based on having a confirmed disease-causing genetic change that results in beta cells not working properly or a suitably matched control same sex close in age and weight
Consent Prospective study participants will be provided with the appropriate participant information sheet PIS and Sub-Study Flowchart detailing the study and procedures specific to the participants genotype If interested in participating the ENDURE study team will contact them to discuss the study in detail and answer any questions and address concerns raised to allow the prospective participant to make an informed decision regarding taking part in the study For the Imaging Sub-Study following receipt of verbal consent participants will be asked to complete a MRI Safety Checklist Screening Form that is necessary to screen them prior to booking their MRI scan Prospective study participants are individuals with a rare genetic mutation that is associated with a monogenic beta cell disorder The cohort of prospective study participants is diverse in terms of background primary language home country To have an inclusive study set-up the study team will provide documents that are translated into the participants or guardians primary language where English is not the primary language Additionally a National Health Service NHS appointed interpreterinterpretation service eg Language Line will be arranged for phone calls and the study visit to ensure clear communication The participants clinician may also attend and provide translation
Withdrawal of consent All participants and their legal guardians will be informed of their right to withdraw from the study without stating a reason at any time up to and including data and sample analysis without prejudice or jeopardy to any future clinical care If a participant permanently withdraws from the study the reason if provided will be recorded
Research visits All study participants will be invited to the National Institute for Health and Care Research NIHR Exeter Clinical Research Facility Exeter CRF or alternative convenient location to provide written informed consentassent and undergo Core Study data collection measurements and provide blood samples collected by a nurse or doctor paediatric if necessary fully trained in this procedure This Core Study visit should take approximately 40 minutes to 1 hour
MRI Depending on their genotype participants will be invited to take part in the Imaging Sub-Study to have an MRI Magnetic Resonance Imaging scan to measure organ size and body fat distribution The MRI appointment may be arranged as a separate visit if more convenient for the participant
Patients with genetic variants that result in neonatal diabetes often lack insulin in utero as well as after birth These patients are typically born at proximately half normal birth weight as the foetus in the womb lack insulin and this is a major growth factor for the foetus To allow assessment of the impact of lack of insulin in utero on post-natal growth fat distribution and the pancreatic size participants with genetic subtypes that stop insulin secretion in utero will be invited to have an MRI optional during their visit A CE marked MRI scanner at the Mirielle Gillings Neuroimaging Centre MGNC will be used to acquire multiple standard vendor sequences of the participants body to look at fat distribution and measure organ size 40-60 minutes During the procedure the participant can ask to stop the procedure at any time between and during scans and can also have breaks between the scans A priority scan list will be followed to obtain images according to importance to address the research questions
Data Collection and Recording All participants will be pseudo-anonymised by assigning a unique study identifier ID under which all data and samples collected will be recorded and stored The relevant visit Case Report Form CRF will capture all the information required to ensure that all the documented statistical information dictated in the protocol is captured and documented at each visit This also serves to monitor patient eligibility and safety at Sponsor level Hard copies will be stored in the Trial Master File TMF
Sample collection and storage All samples will be collected and processed by a suitably qualified and trained member of the clinicalresearch team whose role is documented on the study delegation log The amount of blood to be drawn from participants is solely for research purposes and will not exceed the recommended limits in accordance with World Health Organization WHO guidelines according to age andor weight of study participants Children will be offered use of a topical anaesthetic as is common practise during phlebotomy of children Blood collection will be made into specific blood collection tubes according to the study aim
The Exeter Blood Sciences Laboratory will provide analyses from routine biochemistry tests available in the NHS test repertoire All assays are CE marked fully validated and accredited by Clinical Pathology Accreditation CPA Clinical results will be available within 21 days of receipt of the sample
The investigators laboratories based at the University of Exeter will receive blood samples to isolate blood fractions according to established protocols according to manufacturers description A detailed Standard Operating Procedure SOP will be provided detailing clear instruction to the logistics of sample labelling logging and management of sample processing and storage of isolated blood fractions
Robust procedures in compliance with the Human Tissue Act 2004 are always followed to monitor and maintain the integrity and traceability of the samples stored in a licensed area including their disposal All samples will be processed logged and frozen using sample-appropriate storage procedures Human Tissue Authority HTA approved locations for storage are available within the investigators laboratories at the University of Exeter Medical School All saved samples will be stored under the study ID with the file linking the study code to personal identifiable information held securely by the PI accessible only to personnel with training in data protection who require this information to perform their duties Those with access to personal identifiable data will be documented on the study Delegation Log
The Study ID will provide a robust pseudo-anonymised system for management and location tracking of all study samples The research team will monitor consent status via the study database Where samples are unable to be collected this should be documented under the participant Study ID with reason for non-collection provided
Transfer of custodianship of stored samples with consent to the Genetic Beta Cell Research Bank GBCRB managed by The Royal Devon University Healthcare NHS Foundation Trusts Exeter Genomics Laboratory may occur during the study or at the end of the study as defined above Stored samples will then be made available for further separate ethically-approved research
End of Study The parameter marking the end of the study is the 3 months after the final participants final visit or 3 months prior to end of the funded period whichever is later to allow for final collection of data and analysis
Incidental Findings Investigations in this study are aimed to answer research questions and not guide clinical care Therefore individual results will not be reported routinely to the participant and their clinicians However incidental findings outside the range of the normal population may occur All incidental findings will be discussed with the Chief Investigator CI or medically qualified delegate to assess whether immediate clinical action is required If required the test results would be communicated back to the participant and their healthcare providers to enable initiation of follow-up andor treatment Participants will not expect to receive individual results unless clinical action is needed A statement to this effect is included in the information sheet and consent form
Safety The timeframe for recording a Serious Adverse Event SAE will be from the time of consent to one week following the last visit of a study participant Any reportable adverse effects noted will be reported within 24 hours to the CI and the Sponsor as per standard NHS RD protocols Nominated co-investigators will be authorised to sign the SAE forms in the absence of the CI at the co-ordinating site or the PI at the participating sites
Indemnity The lead Sponsor University of Exeter provides cover under its No Fault Compensation Insurance which provides for payment of damages or compensation in respect of any claim made by a research participant for bodily injury arising out of participation in a clinical trial or healthy volunteer study with certain restrictions Public liability insurance is provided to cover the design and management of the study
NHS indemnity covers potential legal liability i for harm to participants arising from the design of the research and ii of investigatorsresearch staff for harm to participants arising from the conduct of the research
Access to Final Study Dataset and Archiving Where consent is given by the participantparentguardian their remaining samples and data from the project will be gifted to the Genetic Beta Cell Research Bank GBCRB an approved tissue bank REC ref Wales Research Ethics Committee 5 22WA0268 in Exeter to be used for future research The GBCRB is managed by The Royal Devon University Healthcare NHS Foundation Trusts Exeter Genomics Laboratory Access to samplesdata is through application to the Genetic Beta Cell Research Bank steering committee
When the research study is complete it is a requirement of the UK Policy Framework for Health Social Care and Sponsor Trust Policy that the records are kept for a further 15 years At the end of the study the study data will be archived by the CI at the University of Exeter
Dissemination Policy Results will be written up and submitted for publication in open-access peer-reviewed journals and prior to open access preprint servers eg such as medRxiv or bioRxiv Abstracts will be submitted to national and international conferences Results will also be presented to colleagues clinical and research at regular in-house meetings Ongoing updates on study progress will also be made to Exeter PPIE group for continued feedback
Some data will also be deposited in electronic archives that are available to other researchers upon request to ensure data is used only to advance scientific and medical understanding
Written information outlining the key findings of the study will be sent to all participants and uploaded to the NIHR Exeter CRF and study websites
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 340277 | OTHER | None | None |
| 24NW0117 | OTHER | None | None |
| 224600Z21Z | OTHER_GRANT | None | None |
| R-2304-05983 | OTHER_GRANT | None | None |
| 230006516 | OTHER | None | None |