NCT02723110

Brief Summary

Recent genetic association studies have identified variants in the Peptidyl-Glycine alpha-amidating mono-oxygenase (PAM) gene that increase the risk of diabetes likely through a defect in beta-cell function. This has been followed up and supported by novel kinetic assays and cellular studies. This investigation will recall heterozygous carriers of the risk allele at rs78408340 and age, BMI and gender matched controls from the Oxford Biobank. The study will compare the incretin effect, glucagon-like peptide-1(GLP-1), insulin, glucose levels and PAM protein activity in individuals both with and without the risk variant. The aim of the study is to gain mechanistic insight into the effect of the variant on human physiology and diabetes pathogenesis.

Trial Health

43
At Risk

Trial Health Score

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

Trial has exceeded expected completion date
Enrollment
40

participants targeted

Target at P25-P50 for all trials

Timeline
Completed

Started Jun 2015

Geographic Reach
1 country

1 active site

Status
unknown

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 Start

First participant enrolled

June 1, 2015

Completed
9 months until next milestone

First Submitted

Initial submission to the registry

February 12, 2016

Completed
2 months until next milestone

First Posted

Study publicly available on registry

March 30, 2016

Completed
3 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2016

Completed
Last Updated

June 22, 2016

Status Verified

June 1, 2016

Enrollment Period

1.1 years

First QC Date

February 12, 2016

Last Update Submit

June 21, 2016

Conditions

Type 2 Diabetes

Keywords

Type 2 Diabetes Risk

Outcome Measures

Primary Outcomes (1)

  • Calculated Incretin Effect

    Will be calculated from the amount of IV glucose required to reproduce OGTT glycaemic profile

    3 months

Secondary Outcomes (4)

  • Insulin concentration

    3 months

  • Glucose concentrations

    3 months

  • GLP-1 (glucagon-like peptide-1) amidated and unamidated concentration

    3 months

  • PAM enzyme activity assay

    3 months

Study Arms (2)

rs78408340 heterozygous carriers

Other: 4 Hour Frequently Sampled Oral Glucose Tolerance TestOther: Isoglycaemic Clamp

homozygous non-risk allele carriers

Other: 4 Hour Frequently Sampled Oral Glucose Tolerance TestOther: Isoglycaemic Clamp

Interventions

4 Hour Frequently Sampled Oral Glucose Tolerance TestOTHER

Blood glucose level(BGL) every 5 min, blood for hormone, biochemical analysis at -15,0,15,30,45,60,90,120,180, 240

Also known as: OGTT
homozygous non-risk allele carriersrs78408340 heterozygous carriers
Isoglycaemic ClampOTHER

Glucose infusion over 4 hours to reproduce OGTT glucose curve to allow measurement of incretin effect. BGL every 5 min, blood for hormone, biochemical analysis at -15,0,15,30,45,60,90,120,180, 240

Also known as: Matched clamp
homozygous non-risk allele carriersrs78408340 heterozygous carriers

Eligibility Criteria

Age30 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Healthy volunteers enrolled in the Oxford Biobank

You may qualify if:

  • Adult, age 30-65 inclusive, healthy, appropriate genotype
  • Mental capacity to consent

You may not qualify if:

  • Demographics: \<30 and \>65 years old
  • Medical history: Bariatric surgery, surgery on gut/ stomach; history of recent significant weight loss (\>10% of weight in last year); known cardiovascular disease
  • Medications: Currently prescribed glucose-lowering medication, oral/IV corticosteroid treatment, any medication effecting gastric motility or glucose metabolism

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

OCDEM, University of Oxford

Oxford, Oxfordshire, OX3 7LE, United Kingdom

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

EDTA plasma, serum, lithium heparin

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Glucose Tolerance Test

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

Blood Chemical AnalysisClinical Chemistry TestsClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisDiagnostic Techniques, EndocrineInvestigative Techniques

Central Study Contacts

Fredrik Karpe

CONTACT

01865 857222fredrik.karpe@ocdem.ox.ac.uk

Mahesh M Umapathysivam

CONTACT

01865857261mahesh.umapathysivam@spc.ox.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

February 12, 2016

First Posted

March 30, 2016

Study Start

June 1, 2015

Primary Completion

July 1, 2016

Study Completion

July 1, 2016

Last Updated

June 22, 2016

Record last verified: 2016-06

Locations

GB(1)