Type 2 Diabetes MellitusLOGICNCT03705195
Study of Sulphonylurea Synergy With Incretins
A study testing Gliclazide in people with Type 2 Diabetes Mellitus, run by University of Dundee at 1 site in United Kingdom.
Trial summary
The Study of Sulphonylurea Synergy with Incretins (LOGIC) is a Proof-of-Concept Physiological study in the form of two matched isoglycaemic clamps. A matched clamp consists of an of oral glucose tolerance test followed by an isoglycaemic intravenous glucose infusion (IGII). Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Type 2 Diabetes Mellitus
- What is being tested?
- Gliclazide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 3 Aug 2018to 26 Jun 2019
- Phase
- Interventional
- 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 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 40 - 80,
- Age of Diabetes Diagnoses ≥ 35
- T2DM on no treatment or metformin monotherapy
- White British
- HbA1c ≤ 8% (64mmol/mol)
- eGFR ≥ 50ml/min-1
- ALT ≤ 2.5 x ULN
- Able to consent
Who cannot join
- Type 1 Diabetes Mellitus
- HbA1c > 8.0% (> 64mmol/mol)
- eGFR <50ml/min-1
- ALT >2.5 x ULN
- Anaemia (Haemoglobin <12.0 g/dL for women, <13.0 g/dL for men)
- Pregnancy, lactation or a female planning to conceive within the study period
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- Established pancreatic disease
- Participating in clinical phase of another interventional trial/study or have done so within the last 30 days
- Any other significant medical reason for exclusion as determined by the investigator
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Ninewells Hospital and Medical School
Dundee, DD1 9SY
About this study
The Study of Sulphonylurea Synergy with Incretins (LOGIC) is a Proof-of-Concept Physiological study in the form of two matched isoglycaemic clamps. A matched clamp consists of an of oral glucose tolerance test followed by an isoglycaemic intravenous glucose infusion (IGII). The study will investigate whether there is synergy between a physiological sulphonylurea (SU) stimulus and the incretin effect, causing augmentation of insulin secretion in patients with type 2 diabetes mellitus (T2DM). The study will take place at The Clinical Research Centre at Ninewells Hospital in Dundee over five visits. It will evaluate 20 patients with T2DM on no diabetes therapy, or metformin monotherapy.
All participants will undergo two matched clamps. The first matched clamp will be with no intervention. The second intervention matched clamp, low-dose liquid gliclazide will be administered 1-hour prior to each test. The sulphonylurea, Gliclazide, in this this instance will be used as a physiological stimulus and will only be given on two occasions as part of the second matched clamp. The first eight participants will participate in the dose-ranging phase. They will receive either 10mg or 20mg gliclazide as a stimulus to augment the incretin effect. A further twelve participants will then be recruited to complete the study utilising the dose which caused the greatest increment in insulin secretion. LOGIC will also evaluate the cohort for effect of KCNJ11 genotype on physiological response.
Read the detailed description
The Study of Sulphonylurea Synergy with Incretins (LOGIC) is a Proof-of-Concept Physiological study in the form of two matched isoglycaemic clamps. A matched clamp consists of an of oral glucose bolus test followed by an isoglycaemic intravenous glucose infusion (IGII) the next day. The study will investigate whether there is synergy between a physiological sulphonylurea (SU) stimulus and the incretin effect, causing augmentation of insulin secretion in patients with type 2 diabetes mellitus (T2DM).
The study will take place at The Clinical Research Centre at Ninewells Hospital in Dundee over five visits. It will evaluate 20 patients with T2DM on no diabetes therapy, or metformin monotherapy.
The first visit is a screening visit to ensure the participant meets inclusion and exclusion criteria, and, if so, to obtain written informed consent for study. Visits 2-5 will all occur following an overnight 10-hour fast at home. The second and third visits will make up the first matched clamp. In visit 2, the participant will undergo a 75-gram oral glucose bolus with frequent blood sampling to assess the glucose variance, insulin secretion and incretin hormone response from an oral glucose stimulus. Blood glucose level (BGL) will be sampled every 5 minutes along with hormone biochemical analysis at regular defined time points. The third visit consists of an IGII to replicate the glucose curve from the OGTT to allow measurement of incretin effect. BGL will again be sampled every 5 minutes with regular biochemical analysis of hormones.
The investigators aim to establish whether a low-dose of sulphonylurea will have a synergistic role on insulin secretion with endogenously secreted GLP-1 and GIP, therefore visits four and five will complete the same matched clamp, however, low-dose liquid gliclazide will be administered 1-hour prior to each test. The sulphonylurea, Gliclazide, in this this instance will be used as a physiological stimulus and will only be given on two occasions as part of the second matched clamp. The first eight participants will receive either 10mg or 20mg gliclazide as a stimulus to augment the incretin effect. A further twelve patients will then be recruited to complete the study utilising the dose which caused the greatest increment in insulin secretion.
The comparison of these tests will investigate the hypothesis that there is a synergistic effect between low-dose sulphonylurea and augmentation of the incretin effect on the beta cell. LOGIC will also evaluate the cohort for effect of KCNJ11 genotype on physiological response. Participants will be consented for genotyping as part of this study.
- Conditions
- Type 2 Diabetes Mellitus
- Being tested
- Gliclazide
- 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.
GliclazideDrug
Also called Diamicron, Zicron
Low dose liquid gliclazide will be used with the second matched clamp (OGTT/IGII) in visits 4 \& 5.
| Study group | Role | What they receive |
|---|---|---|
| No Intervention | No intervention | All participants in study will complete two matched clamp studies (OGTT + IGII). The first matched clamp without any intervention the second matched clamp with low dose gliclazide |
| Low Dose Gliclazide | Experimental | The first 8 participants will complete the dose-ranging phase of LOGIC study. Low dose gliclazide is being used a physiological stimulus. In the dose-ranging phase, 4 participants will receive 10mg gliclazide, the remaining 4 will receive 20mg gliclazide. The allocation to 10mg or 20mg will be randomised and unblinded. The study will analyse after the first 8 participants to assess which dose produces the greatest augmentation of insulin secretion when acting synergistically with the incretin effect.
The further 12 participants will complete the study with the identified best dose. Receives: Drug: Gliclazide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in insulin secretion and incretin effect between two matched clamps (presence and absence of low dose gliclazide)
Comparison of two matched clamps (oral glucose tolerance test + isoglycaemic intravenous glucose infusion). Matched clamp 1 - control. Matched clamp 2 - low dose gliclazide. Levels of insulin/c-peptide, incretin hormones and plasma glucose will be compared in the presence and absence of low dose gliclazide
Measured: Through four study visits completed over 4 weeks
Secondary outcomes (1)
Insulin secretory response analysed by KCNJ11 Genotype (E23K, E23E, K23K)
Difference in insulin secretory response to low dose gliclazide calculated by insulin/cpeptide levels in matched clamp(gliclazide). Differences will then be compared by participants genotype e.g. insulin secretory response for E23K, E23E, K23K variants.
Measured: Through four study visits completed over 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2018
- Study start3 Aug 2018
- Primary completion26 Jun 2019
- Study completion26 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Proof-of-Concept Physiological Study
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Dundee
- Sponsor type
- University, hospital or other
- Collaborators
- NHS Tayside
- Responsible party
- Principal investigator, Ruth Cordiner, University of Dundee
- Investigators
- Ewan R Pearson, Study chair, University of Dundee
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03705195
- Sponsor's protocol ID
- 2018DM01
- Acronym
- LOGIC
- Status last verified
- Feb 2020
- First submitted
- 3 Jul 2018
- Last updated
- 24 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Aaboe K, Knop FK, Vilsboll T, Volund A, Simonsen U, Deacon CF, Madsbad S, Holst JJ, Krarup T. KATP channel closure ameliorates the impaired insulinotropic effect of glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes. J Clin Endocrinol Metab. 2009 Feb;94(2):603-8. doi: 10.1210/jc.2008-1731. Epub 2008 Dec 2.
PubMed 19050053Gloyn AL, Pearson ER, Antcliff JF, Proks P, Bruining GJ, Slingerland AS, Howard N, Srinivasan S, Silva JM, Molnes J, Edghill EL, Frayling TM, Temple IK, Mackay D, Shield JP, Sumnik Z, van Rhijn A, Wales JK, Clark P, Gorman S, Aisenberg J, Ellard S, Njolstad PR, Ashcroft FM, Hattersley AT. Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes. N Engl J Med. 2004 Apr 29;350(18):1838-49. doi: 10.1056/NEJMoa032922.
PubMed 15115830Fritsche A, Stefan N, Hardt E, Schutzenauer S, Haring H, Stumvoll M. A novel hyperglycaemic clamp for characterization of islet function in humans: assessment of three different secretagogues, maximal insulin response and reproducibility. Eur J Clin Invest. 2000 May;30(5):411-8. doi: 10.1046/j.1365-2362.2000.00649.x.
PubMed 10809901Holst JJ, Vilsboll T, Deacon CF. The incretin system and its role in type 2 diabetes mellitus. Mol Cell Endocrinol. 2009 Jan 15;297(1-2):127-36. doi: 10.1016/j.mce.2008.08.012. Epub 2008 Aug 20.
PubMed 18786605Henquin JC. Regulation of insulin secretion: a matter of phase control and amplitude modulation. Diabetologia. 2009 May;52(5):739-51. doi: 10.1007/s00125-009-1314-y. Epub 2009 Mar 14.
PubMed 19288076Cordiner RLM, Mari A, Tura A, Pearson ER. The Impact of Low-dose Gliclazide on the Incretin Effect and Indices of Beta-cell Function. J Clin Endocrinol Metab. 2021 Jun 16;106(7):2036-2046. doi: 10.1210/clinem/dgab151.
PubMed 33693776
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Sulphonylurea Synergy With Incretins
- ClinicalTrials.gov ID
- NCT03705195
- Acronym / sponsor ID
- LOGIC / 2018DM01
- Conditions
- Type 2 Diabetes Mellitus
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of DundeeUniversity, hospital or other
- Collaborators
- NHS Tayside
- Study start
- 3 Aug 2018 (actual)
- Primary completion
- 26 Jun 2019 (actual)
- Study completion
- 26 Jun 2019 (actual)
- First posted
- 15 Oct 2018 (actual)
- 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.
The Study of Sulphonylurea Synergy with Incretins (LOGIC) is a Proof-of-Concept Physiological study in the form of two matched isoglycaemic clamps. A matched clamp consists of an of oral glucose tolerance test followed by an isoglycaemic intravenous glucose infusion (IGII). The study will investigate whether there is synergy between a physiological sulphonylurea (SU) stimulus and the incretin effect, causing augmentation of insulin secretion in patients with type 2 diabetes mellitus (T2DM). The study will take place at The Clinical Research Centre at Ninewells Hospital in Dundee over five visits. It will evaluate 20 patients with T2DM on no diabetes therapy, or metformin monotherapy.
All participants will undergo two matched clamps. The first matched clamp will be with no intervention. The second intervention matched clamp, low-dose liquid gliclazide will be administered 1-hour prior to each test. The sulphonylurea, Gliclazide, in this this instance will be used as a physiological stimulus and will only be given on two occasions as part of the second matched clamp. The first eight participants will participate in the dose-ranging phase. They will receive either 10mg or 20mg gliclazide as a stimulus to augment the incretin effect. A further twelve participants will then be recruited to complete the study utilising the dose which caused the greatest increment in insulin secretion. LOGIC will also evaluate the cohort for effect of KCNJ11 genotype on physiological response.
Detailed description
The Study of Sulphonylurea Synergy with Incretins (LOGIC) is a Proof-of-Concept Physiological study in the form of two matched isoglycaemic clamps. A matched clamp consists of an of oral glucose bolus test followed by an isoglycaemic intravenous glucose infusion (IGII) the next day. The study will investigate whether there is synergy between a physiological sulphonylurea (SU) stimulus and the incretin effect, causing augmentation of insulin secretion in patients with type 2 diabetes mellitus (T2DM).
The study will take place at The Clinical Research Centre at Ninewells Hospital in Dundee over five visits. It will evaluate 20 patients with T2DM on no diabetes therapy, or metformin monotherapy.
The first visit is a screening visit to ensure the participant meets inclusion and exclusion criteria, and, if so, to obtain written informed consent for study. Visits 2-5 will all occur following an overnight 10-hour fast at home. The second and third visits will make up the first matched clamp. In visit 2, the participant will undergo a 75-gram oral glucose bolus with frequent blood sampling to assess the glucose variance, insulin secretion and incretin hormone response from an oral glucose stimulus. Blood glucose level (BGL) will be sampled every 5 minutes along with hormone biochemical analysis at regular defined time points. The third visit consists of an IGII to replicate the glucose curve from the OGTT to allow measurement of incretin effect. BGL will again be sampled every 5 minutes with regular biochemical analysis of hormones.
The investigators aim to establish whether a low-dose of sulphonylurea will have a synergistic role on insulin secretion with endogenously secreted GLP-1 and GIP, therefore visits four and five will complete the same matched clamp, however, low-dose liquid gliclazide will be administered 1-hour prior to each test. The sulphonylurea, Gliclazide, in this this instance will be used as a physiological stimulus and will only be given on two occasions as part of the second matched clamp. The first eight participants will receive either 10mg or 20mg gliclazide as a stimulus to augment the incretin effect. A further twelve patients will then be recruited to complete the study utilising the dose which caused the greatest increment in insulin secretion.
The comparison of these tests will investigate the hypothesis that there is a synergistic effect between low-dose sulphonylurea and augmentation of the incretin effect on the beta cell. LOGIC will also evaluate the cohort for effect of KCNJ11 genotype on physiological response. Participants will be consented for genotyping as part of this study.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Proof-of-Concept Physiological Study
| Arm | Type | Receives |
|---|---|---|
| No Intervention | No intervention | –All participants in study will complete two matched clamp studies (OGTT + IGII). The first matched clamp without any intervention the second matched clamp with low dose gliclazide |
| Low Dose Gliclazide | Experimental | Drug: GliclazideThe first 8 participants will complete the dose-ranging phase of LOGIC study. Low dose gliclazide is being used a physiological stimulus. In the dose-ranging phase, 4 participants will receive 10mg gliclazide, the remaining 4 will receive 20mg gliclazide. The allocation to 10mg or 20mg will be randomised and unblinded. The study will analyse after the first 8 participants to assess which dose produces the greatest augmentation of insulin secretion when acting synergistically with the incretin effect. The further 12 participants will complete the study with the identified best dose. |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age 40 - 80,
- Age of Diabetes Diagnoses ≥ 35
- T2DM on no treatment or metformin monotherapy
- White British
- HbA1c ≤ 8% (64mmol/mol)
Key exclusion criteria (9 listed)
- Type 1 Diabetes Mellitus
- HbA1c > 8.0% (> 64mmol/mol)
- eGFR <50ml/min-1
- ALT >2.5 x ULN
- Anaemia (Haemoglobin <12.0 g/dL for women, <13.0 g/dL for men)
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 |
|---|---|---|
| GliclazideAlso: Diamicron, ZicronLow dose liquid gliclazide will be used with the second matched clamp (OGTT/IGII) in visits 4 \& 5. | Drug | Low Dose Gliclazide |
Primary outcome
Difference in insulin secretion and incretin effect between two matched clamps (presence and absence of low dose gliclazide)
Time frame: Through four study visits completed over 4 weeks
Comparison of two matched clamps (oral glucose tolerance test + isoglycaemic intravenous glucose infusion). Matched clamp 1 - control. Matched clamp 2 - low dose gliclazide. Levels of insulin/c-peptide, incretin hormones and plasma glucose will be compared in the presence and absence of low dose gliclazide
1 secondary outcome
Insulin secretory response analysed by KCNJ11 Genotype (E23K, E23E, K23K)
Time frame: Through four study visits completed over 4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2020.
- Background: PubMed 19050053Aaboe K, Knop FK, Vilsboll T, Volund A, Simonsen U, Deacon CF, Madsbad S, Holst JJ, Krarup T. KATP channel closure ameliorates the impaired insulinotropic effect of glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes. J Clin Endocrinol Metab. 2009 Feb;94(2):603-8. doi: 10.1210/jc.2008-1731. Epub 2008 Dec 2.
- Background: PubMed 15115830Gloyn AL, Pearson ER, Antcliff JF, Proks P, Bruining GJ, Slingerland AS, Howard N, Srinivasan S, Silva JM, Molnes J, Edghill EL, Frayling TM, Temple IK, Mackay D, Shield JP, Sumnik Z, van Rhijn A, Wales JK, Clark P, Gorman S, Aisenberg J, Ellard S, Njolstad PR, Ashcroft FM, Hattersley AT. Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes. N Engl J Med. 2004 Apr 29;350(18):1838-49. doi: 10.1056/NEJMoa032922.
- Background: PubMed 10809901Fritsche A, Stefan N, Hardt E, Schutzenauer S, Haring H, Stumvoll M. A novel hyperglycaemic clamp for characterization of islet function in humans: assessment of three different secretagogues, maximal insulin response and reproducibility. Eur J Clin Invest. 2000 May;30(5):411-8. doi: 10.1046/j.1365-2362.2000.00649.x.
- Background: PubMed 18786605Holst JJ, Vilsboll T, Deacon CF. The incretin system and its role in type 2 diabetes mellitus. Mol Cell Endocrinol. 2009 Jan 15;297(1-2):127-36. doi: 10.1016/j.mce.2008.08.012. Epub 2008 Aug 20.
- Background: PubMed 19288076Henquin JC. Regulation of insulin secretion: a matter of phase control and amplitude modulation. Diabetologia. 2009 May;52(5):739-51. doi: 10.1007/s00125-009-1314-y. Epub 2009 Mar 14.
- Derived from this study: PubMed 33693776Cordiner RLM, Mari A, Tura A, Pearson ER. The Impact of Low-dose Gliclazide on the Incretin Effect and Indices of Beta-cell Function. J Clin Endocrinol Metab. 2021 Jun 16;106(7):2036-2046. doi: 10.1210/clinem/dgab151.
- Individual participant dataSharing planned: No
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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.
Ewan R Pearson study chair
University of Dundee
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Gliclazide in people with Type 2 Diabetes Mellitus, run by University of Dundee 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 8 inclusion and 9 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: finished, as of the sponsor's last update on 24 Feb 2020. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in insulin secretion and incretin effect between two matched clamps (presence and absence of low dose gliclazide) (time frame: Through four study visits completed over 4 weeks). 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 NCT03705195, which also lists 6 linked publications.
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 24 Feb 2020.