Type 2 DiabetesDIVA - PAMNCT02723110
Defining the Physiological Mechanisms of Risk Genes for Hyperglycaemia, Insulin Resistance and Type 2 Diabetes
An observational study of Type 2 Diabetes, run by University of Oxford at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- 4 Hour Frequently Sampled Oral Glucose Tolerance Test and Isoglycaemic Clamp
- Type of treatment
- Pill or oral medicine, Injection or infusion
- How many people
- 40 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jun 2015to Jul 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Healthy volunteers enrolled in the Oxford Biobank
Who may be able to join
- Adult, age 30-65 inclusive, healthy, appropriate genotype
- Mental capacity to consent
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
OCDEM, University of Oxford
Oxford, Oxfordshire, OX3 7LE
Fredrik Karpe, 01865 857222, fredrik.karpe@ocdem.ox.ac.uk
Mahesh M Umapathysivam, mahesh.umapathysivam@spc.ox.ac.uk
About this study
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.
Read the detailed description
Note: The study will utilize an adaptive study design with an interim analysis at 40 volunteers (20 v 20) with the possibility of adding an additional 20 volunteers to the study (10 v 10) if the criteria for futility or clear effect are not met.
The criteria are; stop and reject null hypothesis if t > 2.490 and stop and accept null hypothesis if t < 1.033. If the t falls between these values an additional 20 volunteers (10 v10) will be recruited. The decision to stop or additional volunteers will be based on the incretin effect (primary outcome).
- Conditions
- Type 2 Diabetes
- Being tested
- 4 Hour Frequently Sampled Oral Glucose Tolerance Test, Isoglycaemic Clamp
- Keywords
- Type 2 Diabetes Risk
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
4 Hour Frequently Sampled Oral Glucose Tolerance TestOther
Also called OGTT
Blood glucose level(BGL) every 5 min, blood for hormone, biochemical analysis at -15,0,15,30,45,60,90,120,180, 240
Isoglycaemic ClampOther
Also called Matched clamp
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
| Study group | Role | What they receive |
|---|---|---|
| rs78408340 heterozygous carriers | Not described Receives: Other: 4 Hour Frequently Sampled Oral Glucose Tolerance Test; Other: Isoglycaemic Clamp | |
| homozygous non-risk allele carriers | Not described Receives: Other: 4 Hour Frequently Sampled Oral Glucose Tolerance Test; Other: Isoglycaemic Clamp |
What is being measured
The primary outcome is the main question the study is designed to answer.
Calculated Incretin Effect
Will be calculated from the amount of IV glucose required to reproduce OGTT glycaemic profile
Measured: 3 months
Secondary outcomes (4)
Insulin concentration
Measured: 3 months
Glucose concentrations
Measured: 3 months
GLP-1 (glucagon-like peptide-1) amidated and unamidated concentration
Measured: 3 months
PAM enzyme activity assay
This assay is based off the protocol in the published literature, and is based on the turnover of radio-labelled substrate to quantify the amidating ability of the PAM enzyme
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2016 (estimated)
- Study startJun 2015
- Primary completionJul 2016 (estimated)
- Study completionJul 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- University of Exeter, Medical Research Council
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02723110
- Sponsor's protocol ID
- 15/SC/0072
- Acronym
- DIVA - PAM
- Status last verified
- Jun 2016
- First submitted
- 12 Feb 2016
- Last updated
- 22 Jun 2016
- Results posted
- No
Publications
Umapathysivam MM, Araldi E, Hastoy B, Dawed AY, Vatandaslar H, Mayrhofer JE, Lindquist P, Silva PN, Goga A, Trullinger GO, Godbersen S, Sengupta S, Kaufmann A, Thomsen SK, Hartmann B, Chen YC, Jonsson AE, Kabakci H, Thaman S, Grarup N, Have CT, Pallo LP, Faerch K, Gjesing AP, Nawaz S, Cheeseman J, Neville MJ, Pedersen O, Walker M, Sun H, Jennison C, Hattersley AT, Rehfeld JF, Holman RR, Verchere BC, Hansen T, Karpe F, Holst JJ, Rosenkilde MM, Jones AG, Ristow M, McCarthy MI, Pearson ER, Stoffel M, Gloyn AL. Type 2 diabetes risk alleles in peptidyl-glycine alpha-amidating monooxygenase influence GLP-1 levels and response to GLP-1 receptor agonists. Genome Med. 2026 Mar 29;18(1):40. doi: 10.1186/s13073-026-01630-0.
PubMed 41906117
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Defining the Physiological Mechanisms of Risk Genes for Hyperglycaemia, Insulin Resistance and Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT02723110
- Acronym / sponsor ID
- DIVA - PAM / 15/SC/0072
- Conditions
- Type 2 Diabetes
- Keywords
- Type 2 Diabetes Risk
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- University of Exeter, Medical Research Council
- Study start
- Jun 2015
- Primary completion
- Jul 2016 (estimated)
- Study completion
- Jul 2016 (estimated)
- First posted
- 30 Mar 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Note: The study will utilize an adaptive study design with an interim analysis at 40 volunteers (20 v 20) with the possibility of adding an additional 20 volunteers to the study (10 v 10) if the criteria for futility or clear effect are not met.
The criteria are; stop and reject null hypothesis if t > 2.490 and stop and accept null hypothesis if t < 1.033. If the t falls between these values an additional 20 volunteers (10 v10) will be recruited. The decision to stop or additional volunteers will be based on the incretin effect (primary outcome).
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| rs78408340 heterozygous carriers | – | Other: 4 Hour Frequently Sampled Oral Glucose Tolerance Test, Other: Isoglycaemic Clamp |
| homozygous non-risk allele carriers | – | Other: 4 Hour Frequently Sampled Oral Glucose Tolerance Test, Other: Isoglycaemic Clamp |
Who may qualify
- Ages
- 30 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Healthy volunteers enrolled in the Oxford Biobank
Key inclusion criteria (2 listed)
- Adult, age 30-65 inclusive, healthy, appropriate genotype
- Mental capacity to consent
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 4 Hour Frequently Sampled Oral Glucose Tolerance TestAlso: OGTTBlood glucose level(BGL) every 5 min, blood for hormone, biochemical analysis at -15,0,15,30,45,60,90,120,180, 240 | Other | homozygous non-risk allele carriers, rs78408340 heterozygous carriers |
| Isoglycaemic ClampAlso: Matched clampGlucose 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 | Other | homozygous non-risk allele carriers, rs78408340 heterozygous carriers |
Primary outcome
Calculated Incretin Effect
Time frame: 3 months
Will be calculated from the amount of IV glucose required to reproduce OGTT glycaemic profile
4 secondary outcomes
Insulin concentration
Time frame: 3 months
Glucose concentrations
Time frame: 3 months
GLP-1 (glucagon-like peptide-1) amidated and unamidated concentration
Time frame: 3 months
PAM enzyme activity assay
Time frame: 3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2016.
- Derived from this study: PubMed 41906117Umapathysivam MM, Araldi E, Hastoy B, Dawed AY, Vatandaslar H, Mayrhofer JE, Lindquist P, Silva PN, Goga A, Trullinger GO, Godbersen S, Sengupta S, Kaufmann A, Thomsen SK, Hartmann B, Chen YC, Jonsson AE, Kabakci H, Thaman S, Grarup N, Have CT, Pallo LP, Faerch K, Gjesing AP, Nawaz S, Cheeseman J, Neville MJ, Pedersen O, Walker M, Sun H, Jennison C, Hattersley AT, Rehfeld JF, Holman RR, Verchere BC, Hansen T, Karpe F, Holst JJ, Rosenkilde MM, Jones AG, Ristow M, McCarthy MI, Pearson ER, Stoffel M, Gloyn AL. Type 2 diabetes risk alleles in peptidyl-glycine alpha-amidating monooxygenase influence GLP-1 levels and response to GLP-1 receptor agonists. Genome Med. 2026 Mar 29;18(1):40. doi: 10.1186/s13073-026-01630-0.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Type 2 Diabetes, run by University of Oxford at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Fredrik Karpe (01865 857222, fredrik.karpe@ocdem.ox.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Calculated Incretin Effect (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02723110, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2016.