Study of Sulphonylurea Synergy With DPP4 Inhibitors
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Difference in incretin effect between mixed meal tests
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Sulfonylurea (Drug)
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.
干预措施: DPP4 Inhibitor (Drug)
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.
干预措施: Sulfonylurea (Drug)
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.
干预措施: DPP4 Inhibitor (Drug)
结局指标
主要结局
Difference in incretin effect between mixed meal tests
时间窗: 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.
次要结局
- Insulin secretory response analysed by KCNJ11 genotype(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(Meansurements taken via continuous glucose monitoring sensors worn by participants for duration of 8 week clinical phase)