NCT06478121

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 individual's genetic variant. The study's 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 kg/m2) for specified case-control studies.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
50

participants targeted

Target at P25-P50 for all trials

Timeline
34mo left

Started Nov 2025

Typical duration for all trials

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress15%
Nov 2025Feb 2029

First Submitted

Initial submission to the registry

June 11, 2024

Completed
16 days until next milestone

First Posted

Study publicly available on registry

June 27, 2024

Completed
1.4 years until next milestone

Study Start

First participant enrolled

November 11, 2025

Completed
3.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 28, 2029

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 28, 2029

Last Updated

January 16, 2026

Status Verified

January 1, 2026

Enrollment Period

3.3 years

First QC Date

June 11, 2024

Last Update Submit

January 14, 2026

Conditions

Diabetes MellitusMonogenic DiabetesHyperinsulinism

Keywords

Monogenic DiabetesHyperinsulinismBeta cell disordersGenotype-to-phenotypeCausal genetic variantBeta cell

Outcome Measures

Primary Outcomes (2)

  • Identification and description of biomarkers or cellular features associated with specific rare causal genetic variants.

    Study of cellular features (assessing gene and protein expression by relevant methodologies, including RNA sequencing and Flow Cytometry) in blood samples that occur because of the rare causal genetic variant.

    5 years

  • Identification of alterations in physiological function with specific rare genetic variants.

    Study of the altered physiology (assessed by magnetic resonance imaging) or cellular function (biochemical assessment of pancreatic hormones/enzymes) that are due to the rare causal genetic variant.

    5 years

Study Arms (2)

Case with confirmed disease-causing genetic change

Cases with confirmed disease-causing genetic change that results in beta cells not working properly. Consent, collection of clinical data and blood samples, MRI (optional)

Other: Data and Blood collectionOther: MRI

Control (without the variant of interest)

Sex-matched controls with similar age and BMI (age +/-15%, BMI +/- 3 kg/m2). Consent, collection of clinical data and blood samples, MRI (optional)

Other: Data and Blood collectionOther: MRI

Interventions

Data and Blood collectionOTHER

Data and Blood collection

Case with confirmed disease-causing genetic changeControl (without the variant of interest)
MRIOTHER

MRI (optional)

Case with confirmed disease-causing genetic changeControl (without the variant of interest)

Eligibility Criteria

Age6 Years - 99 Years
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Participants will be selected based on: 1. having a confirmed disease-causing genetic change that results in a beta cell disorder; 2. or being a suitably matched control (same sex; age +/- 15%; BMI +/- 3 kg/m2).

You may qualify if:

  • Mental capacity to give informed consent
  • Of any sex, ethnicity, location.
  • Group 1: Cases will have a genetic variant(s) resulting in a beta cell disorder.
  • Group 2: Controls will not have a genetic variant(s) resulting in a beta cell disorder and will be matched to a Case for sex, age (+/- 15%) and BMI (+/- 3 kg/m2).

You may not qualify if:

  • Lack of mental capacity to give informed consent
  • Age \<6 years; \>99 years
  • Cochlear Implant
  • Aneurysm Clips
  • Neurological stimulator
  • Implanted cardiac devices (ICD, PPM, loop recorders, or any others)
  • Metal heart valve
  • History of metal foreign bodies in orbits
  • Other implanted metal device which prevents MRI
  • Known claustrophobia.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Royal Devon University Healthcare NHS Foundation Trust

Exeter, Devon, EX2 5DW, United Kingdom

RECRUITING

Related Publications (4)

  • Gupsilonemes M, Rahman SA, Kapoor RR, Flanagan S, Houghton JAL, Misra S, Oliver N, Dattani MT, Shah P. Hyperinsulinemic hypoglycemia in children and adolescents: Recent advances in understanding of pathophysiology and management. Rev Endocr Metab Disord. 2020 Dec;21(4):577-597. doi: 10.1007/s11154-020-09548-7.

    PMID: 32185602BACKGROUND

  • De Franco E. From Biology to Genes and Back Again: Gene Discovery for Monogenic Forms of Beta-Cell Dysfunction in Diabetes. J Mol Biol. 2020 Mar 6;432(5):1535-1550. doi: 10.1016/j.jmb.2019.08.016. Epub 2019 Aug 31.

    PMID: 31479665BACKGROUND

  • Hughes AE, De Franco E, Freathy RM; Fetal Insulin and Growth Consortium; Flanagan SE, Hattersley AT. Monogenic disease analysis establishes that fetal insulin accounts for half of human fetal growth. J Clin Invest. 2023 Mar 15;133(6):e165402. doi: 10.1172/JCI165402. No abstract available.

    PMID: 36808723BACKGROUND

  • Wilman HR, Kelly M, Garratt S, Matthews PM, Milanesi M, Herlihy A, Gyngell M, Neubauer S, Bell JD, Banerjee R, Thomas EL. Correction: Characterisation of liver fat in the UK Biobank cohort. PLoS One. 2017 Apr 26;12(4):e0176867. doi: 10.1371/journal.pone.0176867. eCollection 2017.

    PMID: 28445545BACKGROUND

Related Links

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral blood mononuclear cells (PBMC), Serum, Plasma

MeSH Terms

Conditions

Diabetes MellitusHyperinsulinism

Condition Hierarchy (Ancestors)

Glucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Study Officials

  • Andrew Hattersley, FRS, FMed

    University of Exeter

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Matthew Johnson, PhD

CONTACT

+44 (0) 1392 408277m.johnson@exeter.ac.uk

Martin Eichmann, PhD

CONTACT

m.eichmann@exeter.ac.uk

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 11, 2024

First Posted

June 27, 2024

Study Start

November 11, 2025

Primary Completion (Estimated)

February 28, 2029

Study Completion (Estimated)

February 28, 2029

Last Updated

January 16, 2026

Record last verified: 2026-01

Locations

GB(1)