Type 2 DiabetesSSSNCT04192292
Study of Sulphonylurea Synergy With DPP4 Inhibitors
A study testing Sulfonylurea and DPP4 Inhibitor in people with Type 2 Diabetes, run by University of Dundee at 1 site in United Kingdom.
Trial summary
The Study of Sulphonylurea Synergy with DPP4 Inhibitors (SSS Study) will establish whether a very low dose of sulphonylurea will have a synergistic role on augmentation of insulin secretion when given in combination with a DPP4 inhibitor as a primary outcome. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- Sulfonylurea and DPP4 Inhibitor
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 8 Oct 2019to 2 Dec 2020
- 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 and ≦80
- Age of diabetes diagnosis ≧35
- T2DM on no treatment, or metformin monotherapy
- White British
- HbA1c ≦8% (64mmol/mol) in last 6 months
- eGFR ≧50ml/min-1
- ALT ≦2.5*ULN
- Able to consent
Who cannot join
- Does not meet inclusion criteria
- Pregnancy, lactation or a female planning to conceive within the study period
- Previous acute pancreatitis
- 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
- Inability or unwillingness to comply with protocol
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 DPP4 Inhibitors (SSS Study) will establish whether a very low dose of sulphonylurea will have a synergistic role on augmentation of insulin secretion when given in combination with a DPP4 inhibitor as a primary outcome. The study will recruit 30 patients with type 2 diabetes mellitus controlled with no treatment or metformin monotherapy with an HbA1c <64mmol/mol (<8%). In this unblinded, randomised physiological study, participants will receive four 14-day intervention blocks: low dose sulphonylurea alone, DPP4 inhibitor alone, low dose sulphonylurea + DPP4 inhibitor or no treatment change. The primary outcome will be assessed through evaulation of insulin secretion and sensitivity at mixed meal test at the end of each treatment block. Glycaemic variability on continuous glucose monitoring for each intervention block will be evaluated as a secondary outcome. In addition, the primary outcome will be evaulated for KCNJ11 genotype as an additional secondary outcome.
Read the detailed description
The Study of Sulphonylurea Synergy with DPP4 Inhibitors (SSS Study) aims to establish whether a very low dose of SU will have a synergistic role to increase insulin secretion when given in combination with DPP4 inhibitors (DPP4i). This physiological study will assess glucose variability and insulin secretion through mixed meal tests and continuous glucose monitoring.
The SSS Study is a follow-on study from The Study of Sulphonylurea Synergy with Incretins (LOGIC Study 2018DM01, 18/ES/0064, ClinicalTrials.gov NCT03705195) which established that the use of low dose sulphonylurea as a physiological stimulus augments insulin secretion through synergistic action with incretin hormones.
In this study, low dose sulphonylurea will again be used as a physiological stimulus. A DPP4i will be given to increase levels of incretin hormones. The investigator's hypothesis is that a combination of low-dose sulphonylurea with a DPP4i will further augment insulin secretion than with low-dose SU alone. In addition, utilising results from LOGIC Study, the low-dose SU has been shown to promote insulin secretion in a glucose-dependent mechanism via synergy with incretin hormones, therefore glycaemic variability should be minimised.
The SSS study will take place at The Clinical Research Centre in Dundee over 6 visits. It will evaluate 30 patients with T2DM on no diabetes therapy or metformin monotherapy. All participants will continue their existing diabetes treatment for the duration of the study.
SSS Study clinical stage will be 8 weeks. A screening visit will obtain Informed Written Consent for Study, along with baseline medical information and screening bloods to ensure the participant is safe to take part.
There are four, 2-week blocks during the clinical phase of the study:
- Block 1: No change to treatment
- Block 2: Low Dose Sulphonylurea Once Daily
- Block 3: DPP4i Once Daily
- Block 4: Low Dose Sulphonylurea + DPP4i Once Daily
The SSS Study is randomised to intervention order. Participants will crossover to receive each intervention during the study period. They will be randomised using a computer randomisation software.
At the four intensive visits, participants will undergo a two-hour MMT to assess post-prandial glucose variance. In addition, participants will wear CGM (Freestyle Libre Pro Flash Continuous Glucose Monitoring System, Abbot) for the duration of study to assess overall physiological glucose variability. The CGM sensor will be replaced at each study visit. The CGM has a dedicated software, meters will be downloaded to a secure University computer. The software produces an analysis of blood sugar readings for the last 14 days.
Comparison of glycaemic variability and post-prandial insulin secretion after each of the treatment periods will investigate whether low-dose SU and DPP4i further augment insulin secretion compared with low-dose SU alone.
- Conditions
- Type 2 Diabetes
- Being tested
- Sulfonylurea, DPP4 Inhibitor
- Keywords
- Metformin, Sulphonylurea, Gliclazide, DPP4 Inhibitor, Sitagliptin, Continuous Glucose Monitoring, KCNJ11, Incretin Effect
- 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.
SulfonylureaDrug
Also called Diamicron, Nordialex, Gliclazide
Given at very low dose as a physiological stimulus on the beta cell not as medical treatment. 20mg gliclazide is being used in this study.
DPP4 InhibitorDrug
Also called Sitagliptin, Januvia, Janumet, Ristaben
Given as a physiological stimulus to augment endogenous incretin hormone levels, not as a medical treatment. 100mg sitagliptin is being used in this study.
| Study group | Role | What they receive |
|---|---|---|
| No Treatment | No intervention | No change to participants standard care |
| Low dose sulphonylurea alone | Experimental | Participants will be given a single dose of low dose sulphonylurea once daily for 14 days as a physiological stimulus. The sulphonylurea given in this study will be gliclazide 20mg orally once daily. Receives: Drug: Sulfonylurea |
| DPP4 inhibitor alone | Experimental | Participants will be given a single dose of DPP4 inhibitor once daily for 14 days as a physiological stimulus. The DPP inhibitor given in this study will be sitagliption 100mg orally once daily. Receives: Drug: DPP4 Inhibitor |
| Low dose sulphonylurea + DPP4 inhibitor | Experimental | Participants will be given a single dose of low dose sulphonylurea once daily and a single dose of DPP4 inhibitor for 14 days as a physiological stimulus. The sulphonylurea given in this study will be gliclazide 20mg orally once daily and the DPP4 inhibitor will be sitagliptin orally100mg once daily. Receives: Drug: Sulfonylurea; Drug: DPP4 Inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in incretin effect between mixed meal tests
Comparison of four mixed meal tests performed at the end of each intervention block. Meal tests will evaluate 1) No intervention 2) Low dose sulphonylurea alone 3) DPP4 inhibitor alone 4) Low dose sulphonylurea + DPP4 inhibitor. Measures of the incretin effect will be compared between the different blocks.
Measured: Through four mixed meal tests which take place at the end of each 14 day intervention block. The four intervention blocks will be completed during an 8 week clinical phase of study.
Secondary outcomes (2)
Insulin secretory response analysed by KCNJ11 genotype
Difference in insulin secretory response to low dose gliclazide calculated by insulin/cpeptide levels in each meal test visit. Differences will then be compared by participants genotype e.g. insulin secretory response for E23K, E23E, K23K variants.
Measured: Through 4 meal test visits completed over an 8 week clinical phase of study. Outcome will also be evaluated through variability of glucose levels observed on continuous glucose monitoring worn for duration of 8 week clinical phase.
Variation in blood glucose during intervention blocks analysed by continuous glucose monitoring
Comparison time-in-range of blood sugars as low, target and high on continuous glucose monitoring between each intervention block
Measured: Meansurements taken via continuous glucose monitoring sensors worn by participants for duration of 8 week clinical phase
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2019
- Study start8 Oct 2019
- Primary completion2 Dec 2020
- Study completion2 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 DiabetesStudies 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
- Randomised
- Intervention model
- Parallel groups
- Model description
- Physiological Study
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Dundee
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04192292
- Sponsor's protocol ID
- 2018DM13
- Acronym
- SSS
- Status last verified
- Mar 2021
- First submitted
- 9 Oct 2019
- Last updated
- 4 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Sulphonylurea Synergy With DPP4 Inhibitors
- ClinicalTrials.gov ID
- NCT04192292
- Acronym / sponsor ID
- SSS / 2018DM13
- Conditions
- Type 2 Diabetes
- Keywords
- Metformin, Sulphonylurea, Gliclazide, DPP4 Inhibitor, Sitagliptin, Continuous Glucose Monitoring, KCNJ11, Incretin Effect
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of DundeeUniversity, hospital or other
- Study start
- 8 Oct 2019 (actual)
- Primary completion
- 2 Dec 2020 (actual)
- Study completion
- 2 Dec 2020 (actual)
- First posted
- 10 Dec 2019 (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 DPP4 Inhibitors (SSS Study) will establish whether a very low dose of sulphonylurea will have a synergistic role on augmentation of insulin secretion when given in combination with a DPP4 inhibitor as a primary outcome. The study will recruit 30 patients with type 2 diabetes mellitus controlled with no treatment or metformin monotherapy with an HbA1c <64mmol/mol (<8%). In this unblinded, randomised physiological study, participants will receive four 14-day intervention blocks: low dose sulphonylurea alone, DPP4 inhibitor alone, low dose sulphonylurea + DPP4 inhibitor or no treatment change. The primary outcome will be assessed through evaulation of insulin secretion and sensitivity at mixed meal test at the end of each treatment block. Glycaemic variability on continuous glucose monitoring for each intervention block will be evaluated as a secondary outcome. In addition, the primary outcome will be evaulated for KCNJ11 genotype as an additional secondary outcome.
Detailed description
The Study of Sulphonylurea Synergy with DPP4 Inhibitors (SSS Study) aims to establish whether a very low dose of SU will have a synergistic role to increase insulin secretion when given in combination with DPP4 inhibitors (DPP4i). This physiological study will assess glucose variability and insulin secretion through mixed meal tests and continuous glucose monitoring.
The SSS Study is a follow-on study from The Study of Sulphonylurea Synergy with Incretins (LOGIC Study 2018DM01, 18/ES/0064, ClinicalTrials.gov NCT03705195) which established that the use of low dose sulphonylurea as a physiological stimulus augments insulin secretion through synergistic action with incretin hormones.
In this study, low dose sulphonylurea will again be used as a physiological stimulus. A DPP4i will be given to increase levels of incretin hormones. The investigator's hypothesis is that a combination of low-dose sulphonylurea with a DPP4i will further augment insulin secretion than with low-dose SU alone. In addition, utilising results from LOGIC Study, the low-dose SU has been shown to promote insulin secretion in a glucose-dependent mechanism via synergy with incretin hormones, therefore glycaemic variability should be minimised.
The SSS study will take place at The Clinical Research Centre in Dundee over 6 visits. It will evaluate 30 patients with T2DM on no diabetes therapy or metformin monotherapy. All participants will continue their existing diabetes treatment for the duration of the study.
SSS Study clinical stage will be 8 weeks. A screening visit will obtain Informed Written Consent for Study, along with baseline medical information and screening bloods to ensure the participant is safe to take part.
There are four, 2-week blocks during the clinical phase of the study:
- Block 1: No change to treatment
- Block 2: Low Dose Sulphonylurea Once Daily
- Block 3: DPP4i Once Daily
- Block 4: Low Dose Sulphonylurea + DPP4i Once Daily
The SSS Study is randomised to intervention order. Participants will crossover to receive each intervention during the study period. They will be randomised using a computer randomisation software.
At the four intensive visits, participants will undergo a two-hour MMT to assess post-prandial glucose variance. In addition, participants will wear CGM (Freestyle Libre Pro Flash Continuous Glucose Monitoring System, Abbot) for the duration of study to assess overall physiological glucose variability. The CGM sensor will be replaced at each study visit. The CGM has a dedicated software, meters will be downloaded to a secure University computer. The software produces an analysis of blood sugar readings for the last 14 days.
Comparison of glycaemic variability and post-prandial insulin secretion after each of the treatment periods will investigate whether low-dose SU and DPP4i further augment insulin secretion compared with low-dose SU alone.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Physiological Study
| Arm | Type | Receives |
|---|---|---|
| No Treatment | No intervention | –No change to participants standard care |
| Low dose sulphonylurea alone | Experimental | Drug: SulfonylureaParticipants will be given a single dose of low dose sulphonylurea once daily for 14 days as a physiological stimulus. The sulphonylurea given in this study will be gliclazide 20mg orally once daily. |
| DPP4 inhibitor alone | Experimental | Drug: DPP4 InhibitorParticipants will be given a single dose of DPP4 inhibitor once daily for 14 days as a physiological stimulus. The DPP inhibitor given in this study will be sitagliption 100mg orally once daily. |
| Low dose sulphonylurea + DPP4 inhibitor | Experimental | Drug: Sulfonylurea, Drug: DPP4 InhibitorParticipants will be given a single dose of low dose sulphonylurea once daily and a single dose of DPP4 inhibitor for 14 days as a physiological stimulus. The sulphonylurea given in this study will be gliclazide 20mg orally once daily and the DPP4 inhibitor will be sitagliptin orally100mg once daily. |
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 and ≦80
- Age of diabetes diagnosis ≧35
- T2DM on no treatment, or metformin monotherapy
- White British
- HbA1c ≦8% (64mmol/mol) in last 6 months
Key exclusion criteria (7 listed)
- Does not meet inclusion criteria
- Pregnancy, lactation or a female planning to conceive within the study period
- Previous acute pancreatitis
- Established pancreatic disease
- Participating in clinical phase of another interventional trial/study or have done so within the last 30 days.
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 |
|---|---|---|
| SulfonylureaAlso: Diamicron, Nordialex, GliclazideGiven at very low dose as a physiological stimulus on the beta cell not as medical treatment. 20mg gliclazide is being used in this study. | Drug | Low dose sulphonylurea + DPP4 inhibitor, Low dose sulphonylurea alone |
| DPP4 InhibitorAlso: Sitagliptin, Januvia, Janumet, RistabenGiven as a physiological stimulus to augment endogenous incretin hormone levels, not as a medical treatment. 100mg sitagliptin is being used in this study. | Drug | DPP4 inhibitor alone, Low dose sulphonylurea + DPP4 inhibitor |
Primary outcome
Difference in incretin effect between mixed meal tests
Time frame: Through four mixed meal tests which take place at the end of each 14 day intervention block. The four intervention blocks will be completed during an 8 week clinical phase of study.
Comparison of four mixed meal tests performed at the end of each intervention block. Meal tests will evaluate 1) No intervention 2) Low dose sulphonylurea alone 3) DPP4 inhibitor alone 4) Low dose sulphonylurea + DPP4 inhibitor. Measures of the incretin effect will be compared between the different blocks.
2 secondary outcomes
Insulin secretory response analysed by KCNJ11 genotype
Time frame: Through 4 meal test visits completed over an 8 week clinical phase of study. Outcome will also be evaluated through variability of glucose levels observed on continuous glucose monitoring worn for duration of 8 week clinical phase.
Variation in blood glucose during intervention blocks analysed by continuous glucose monitoring
Time frame: Meansurements taken via continuous glucose monitoring sensors worn by participants for duration of 8 week clinical phase
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 4 Mar 2021.
- Study of Sulphonylurea Synergy with IncretinsLink provided by the sponsor.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sulfonylurea and DPP4 Inhibitor in people with Type 2 Diabetes, 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 7 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 4 Mar 2021. 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 incretin effect between mixed meal tests (time frame: Through four mixed meal tests which take place at the end of each 14 day intervention block. The four intervention blocks will be completed during an 8 week clinical phase of study.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Mar 2021.