- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04192292
Study of Sulphonylurea Synergy With DPP4 Inhibitors (SSS)
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
-
Dundee, United Kingdom, DD1 9SY
- Ninewells Hospital and Medical School
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: BASIC_SCIENCE
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
NO_INTERVENTION: No Treatment
No change to participants standard care
|
|
EXPERIMENTAL: Low dose sulphonylurea alone
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.
|
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.
Other Names:
|
EXPERIMENTAL: DPP4 inhibitor alone
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.
|
Given as a physiological stimulus to augment endogenous incretin hormone levels, not as a medical treatment.
100mg sitagliptin is being used in this study.
Other Names:
|
EXPERIMENTAL: Low dose sulphonylurea + DPP4 inhibitor
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.
|
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.
Other Names:
Given as a physiological stimulus to augment endogenous incretin hormone levels, not as a medical treatment.
100mg sitagliptin is being used in this study.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
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.
|
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
|
Comparison time-in-range of blood sugars as low, target and high on continuous glucose monitoring between each intervention block
|
Meansurements taken via continuous glucose monitoring sensors worn by participants for duration of 8 week clinical phase
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2018DM13
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Type 2 Diabetes
-
Antonio Di MauroCompletedType-2 DiabetesItaly
-
DiaMedica Therapeutics IncCompletedDiabetes Type 2Netherlands
-
RenJi HospitalUnknownType 2 Diabetes.China
-
Chengdu Brilliant Pharmaceutical Co., Ltd.Not yet recruitingType 2 Diabetes Mellitus
-
Nanjing First Hospital, Nanjing Medical UniversityRecruitingType 2 Diabetes MellitusChina
-
Xiangya Hospital of Central South UniversityRecruitingType 2 Diabetes MellitusChina
-
University of Alabama at BirminghamCompletedType 2 Diabetes MellitusUnited States
-
Imperial College LondonAstraZeneca; Huma; North West London Collaboration of CCGs (NWL CCGs); Imperial...CompletedType 2 Diabetes MellitusUnited Kingdom
-
Universiti Sains MalaysiaCompleted
-
University of Alabama at BirminghamUnited States Department of Defense; Loma Linda University; Brenda Davis Nutrition... and other collaboratorsCompletedType 2 Diabetes Mellitus
Clinical Trials on Sulfonylurea
-
Royal Devon and Exeter NHS Foundation TrustWellcome Trust; Haukeland University Hospital; Hôpital Necker-Enfants MaladesCompletedDiabetes Mellitus
-
Royal Devon and Exeter NHS Foundation TrustUniversity of Chicago; University of Bergen; University of Rome Tor VergataRecruitingEpilepsy | Intellectual Disability | ADHD | Neurodevelopmental Disorders | Autism Spectrum Disorder | Development DelayUnited States, United Kingdom, Italy, Norway
-
CinnagenUnknownDiabetes Mellitus, Type 2
-
Mitsubishi Tanabe Pharma CorporationCompletedType 2 Diabetes MellitusJapan
-
University Hospital, Gentofte, CopenhagenCompleted
-
All India Institute of Medical Sciences, BhubaneswarChemical ResourcesCompletedType-2 Diabetes MellitusIndia
-
Memorial Sloan Kettering Cancer CenterRecruitingPancreatic Cancer | Pancreatic Cancer Metastatic | Pancreatic Ductal Adenocarcinoma | Pancreatic Carcinoma | Metastatic Pancreatic Cancer | Metastatic Pancreatic Ductal AdenocarcinomaUnited States
-
TakedaCompletedType II Diabetes MellitusKorea, Republic of
-
All India Institute of Medical Sciences, BhubaneswarCompletedDiabetes Mellitus, Type 2India