The effect of SGLT2 inhibitors on glucose and ketone productio

Phase 1

• Conditions: Type 1 and Type 3c diabetes; Therapeutic area: Body processes [G] - Physiological processes [G07]

• Registration Number: EUCTR2015-002094-38-GB
• Lead Sponsor: niversity of Leicester

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-09-18
• Last Update Posted: 30 April 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 30

Inclusion Criteria

•Able in the opinion of the investigator, and willing to give informed consent obtained before any trial-related activities.
•Type 1 diabetes or type 3c (chronic pancreatitis or undergone pancreatic surgery) according to clinical judgment.
•Duration of type 1 or type 3c diabetes (chronic pancreatitis or undergone pancreatic surgery) greater than 12 months.
•Current treatment basal bolus or insulin pump therapy
•Aged 18 years or over
•BMI of less than 35.
•HbA1c of greater or equal to 6.5% and less than 9%.
•Able and willing to complete the trial.
•Patients who are or who have previously been involved in research are eligible provided they have not received an investigational drug within one month of entry into the study

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

•Participants over 65
• Participants who cannot adequately understand verbal and / or written explanations given in English
• Proliferative retinopathy that has required acute treatment within last three months.
•LADA –latent autoimmune diabetes in adults due to differing nature of the illness/Type 1
•Confirmed excessive and compulsive drinking of alcohol i.e. alcohol abuse as determined from GP medical notes by the Fast Alcohol Screening Test (FAST) or history of previous alcohol abuse
•Restricted food intake (e.g. on VLC diets) - as this depletes the person of calories and may affect your data. Consider excluding Individuals on a severe calorie restricted diet <800cals/day. Determined by history
•Diagnosis of osteoporosis confimed by DEXA scan.
•Moderate to severe renal impairment (creatinine clearance [CrCl] < 60 ml/min or estimated glomerular filtration rate [eGFR] < 60 ml/min/1.73 m2.
•History of unstable or rapidly progressing renal disease
•Severe hepatic insufficiency / and or significant abnormal liver function defines as aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and / or alanine aminotransferase (ALT) > 3ULN.
•Positive serologic evidence of current infectious liver disease including Hepatitis B viral antibody IGM, Hepatitis B surface antigen and Hepatitis C virus antibody.
•Congestive heart failure defined as New York Heart Association (NYHA) class III and IV, unstable or acute congestive heart failure. Note: eligible patients with congestive heart failure, especially
•Uncontrolled cardiac arrhythmias.
•Uncontrolled hypertension. (BP greater than 160/90).
•Mental incapacity.
•Pregnancy or breast feeding women
•Those of child-bearing potential not taking adequate contraception precautions. Adequate protection is defined as barrier protection, oral contraceptive pill or intrauterine device
•Volume depleted patients, patients at risk of volume depleting due to co-existing conditions or concomitant medications, such as loop diuretics should have careful monitoring of their volume status
•History of unstable angina.
•Recent Cardiovascular Events in a patient:
•Acute Coronary Syndrome (ACS) within 2 months prior to enrolment
•Hospitalisation for unstable angina or acute myocardial infarction within 2 months prior to enrolment
•Acute Stroke or TIA within two months prior to enrolment
•Less than two months post coronary artery revascularization
•History of diabetic ketoacidosis (DKA) requiring medical intervention (e.g. Accident and Emergency and/or hospitalisation) within 1 month prior to the Screening visit.
•Known or suspected allergy to trial products.
•Known lactose-intolerant individuals.
•Any other medical or psychological conditions that would interfere with the trial participation.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br> Main Objective: To determine the difference in glucose concentration of Dapagliflozin when compared with placebo treatment following insulin withdrawal.<br><br><br> ;Secondary Objective: To determine the difference in glucose and lipid flux of Dapagliflozin when compared to placebo following insulin withdrawal. ;Primary end point(s): Plasma glucose concentration at 600 minutes following insulin cessation or at the time of glycaemic rescue, whichever occurs first.;Timepoint(s) of evaluation of this end point: 600 minutes

Secondary Outcome Measures

Name	Time	Method
<br> Secondary end point(s): 1.Endogenous glucose production<br> 2.Peripheral glucose uptake<br> 3.Urinary glucose excretion<br> 4.Glycerol rate of appearance<br> 5.Non-esterified fatty acid production<br> 6.Ketone body production<br> ;Timepoint(s) of evaluation of this end point: 600 minutes