NCT04192292

Brief 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. 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P25-P50 for not_applicable type-2-diabetes

Timeline
Completed

Started Oct 2019

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 8, 2019

Completed
1 day until next milestone

First Submitted

Initial submission to the registry

October 9, 2019

Completed
2 months until next milestone

First Posted

Study publicly available on registry

December 10, 2019

Completed
12 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 2, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 2, 2020

Completed
Last Updated

March 4, 2021

Status Verified

March 1, 2021

Enrollment Period

1.2 years

First QC Date

October 9, 2019

Last Update Submit

March 3, 2021

Conditions

Keywords

MetforminSulphonylureaGliclazideDPP4 InhibitorSitagliptinContinuous Glucose MonitoringKCNJ11Incretin Effect

Outcome Measures

Primary Outcomes (1)

  • 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.

    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

    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

Study Arms (4)

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.

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.

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.

Drug: SulfonylureaDrug: DPP4 Inhibitor

Interventions

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.

Also known as: Diamicron, Nordialex, Gliclazide
Low dose sulphonylurea + DPP4 inhibitorLow dose sulphonylurea alone

Given as a physiological stimulus to augment endogenous incretin hormone levels, not as a medical treatment. 100mg sitagliptin is being used in this study.

Also known as: Sitagliptin, Januvia, Janumet, Ristaben, Tesavel, Velmetia, Xelevia
DPP4 inhibitor aloneLow dose sulphonylurea + DPP4 inhibitor

Eligibility Criteria

Age40 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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.
  • Inability or unwillingness to comply with protocol

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Ninewells Hospital and Medical School

Dundee, DD1 9SY, United Kingdom

Location

Related Links

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Sulfonylurea CompoundsGliclazideDipeptidyl-Peptidase IV InhibitorsSitagliptin PhosphateSitagliptin Phosphate, Metformin Hydrochloride Drug Combination

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

UreaAmidesOrganic ChemicalsSulfonesSulfur CompoundsBenzenesulfonamidesSulfonamidesBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsProtease InhibitorsEnzyme InhibitorsMolecular Mechanisms of Pharmacological ActionPharmacologic ActionsChemical Actions and UsesHypoglycemic AgentsPhysiological Effects of DrugsTriazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPyrazinesMetforminBiguanidesGuanidinesAmidinesDrug CombinationsPharmaceutical Preparations

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Model Details: Physiological Study
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 9, 2019

First Posted

December 10, 2019

Study Start

October 8, 2019

Primary Completion

December 2, 2020

Study Completion

December 2, 2020

Last Updated

March 4, 2021

Record last verified: 2021-03

Data Sharing

IPD Sharing
Will not share

Locations