The Effect of a SGLT2 Inhibitor on Glucose Flux, Lipolysis and Exercise in Type 2 Diabetes

NCT04219124 | Completed Phase 4

• 1 other identifier: 0585
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

The study is a randomised double blind placebo control cross over trial with 4 weeks washout period. The expected duration of participant participation is 103 days. the study aims to investigate the effect of dapagliflozin, a SGLT2 inhibitor, on glucose flux, lipolysis and exercise in patients with type 2 diabetes.

Conditions

Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• Plasma concentration of 3-hydroxybutyrate

  At visit 4 and visit 6, concentration of 3-hydroxybutyrate in plasma at baseline and during the visit (hourly for 8hr) will be measured by an enzymatic assay using PENTRA clinical chemistry analyser. The mean concentration of 3-hydroxybutyrate between 420-480 mins and the AUC of 3-hydroxybutyrate concentration time curve between 0-240 mins and 0-480 mins where the IMP was given at 0 mins in visits 4 and 6 will be calculated.The response will be compared following 4 weeks treatment with dapagliflozin versus placebo.

  The main analysis will be conducted once all participants have completed the metabolic studies within 2 years

Secondary Outcomes (16)

• Response to exercise testing: Plasma non-esterified fatty acid (NEFA) concentrations

  The main analysis will be conducted once all participants have completed the metabolic studies within 2 years

• Response to exercise testing: Plasma 3-hydroxybutyrate (BOHB) concentration

  The main analysis will be conducted once all participants have completed the metabolic studies within 2 years

• Response to exercise testing: Atrial natriuretic peptide, noradrenaline and adrenaline

  The main analysis will be conducted once all participants have completed the metabolic studies within 2 years

• Response to exercise testing: Glucose concentration, insulin and growth hormone

  The main analysis will be conducted once all participants have completed the metabolic studies within 2 years

• Response to exercise testing:ECG abnormality

  The main analysis will be conducted once all participants have completed the metabolic studies within 2 years

Study Arms (2)

Dapagliflozin

ACTIVE COMPARATOR

Investigational product: Dapagliflozin 10 mg Dosage form and strength: Green, plain, diamond shaped, film coated 10 mg tablet with frequency of 1 tablet per day for 4 weeks

Drug: IMP oral tablet

Placebo

PLACEBO COMPARATOR

Investigational product: Matching placebo for Dapagliflozin 10 mg. Dosage form and strength: Green, plain, diamond shaped, and film coated tablet with frequency of 1 tablet per day for 4 weeks

Drug: Placebo oral tablet

Interventions

IMP oral tablet DRUG

Dapagliflozin 10 MG

Also known as: Farexiga, gliflozin class, SGLT2 inhibitor

Dapagliflozin

Placebo oral tablet DRUG

Matching placebo tablets

Also known as: Matching placebo tablet for dapagliflozin 10 MG

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able in the opinion of the investigator, and willing to give informed consent obtained before any study-related activities.
• Diagnosis of type 2 diabetes greater than 12 months.
• Single, dual or triple therapy glucose lowering agents comprising of sulphonylureas, biguanides and DDP-IV.
• No previous exposure to SGLT2 inhibitors.
• BMI of less than 40.
• HbA1c of greater or equal to 6.5% and less than 9% within 1 month of screening.
• Able to comply with the study and the study procedures.
• Patients who are or who have previously been involved in research are eligible provided a participant has not received an investigational drug within one month of entry into the study.

You may not qualify if:

• Participants over 75.
• Participants under 18.
• Participants who cannot adequately understand verbal and / or written explanations given in English.
• Clinical suspicion of Hypoglycaemic unawareness.
• 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.
• Has a history of chronic pancreatitis.
• Restricted food intake - Determined by history.
• Diagnosis of osteoporosis confirmed by DEXA scan.
• Participants on insulin, insulin analogs or GLP-1 in the preceding 6 months.
• Proliferative retinopathy that has required acute treatment within last three months.
• 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.

Sponsors & Collaborators

• University of Leicester: lead
• Royal Surrey County Hospital NHS Foundation Trust: collaborator
• AstraZeneca: collaborator

Study Sites (1)

CEDAR, Royal Surrey County Hospital

Guildford, Surrey, GU2 7XX, United Kingdom

Location

Related Publications (2)

• Herring RA, Parsons I, Shojaee-Moradie F, Stevenage M, Jackson N, Manders R, Umpleby AM, Fielding BA, Davies M, Russell-Jones DL. Effect of Dapagliflozin on Cardiac Function and Metabolic and Hormonal Responses to Exercise. J Clin Endocrinol Metab. 2023 Mar 10;108(4):888-896. doi: 10.1210/clinem/dgac617.

  PMID: 36274035 DERIVED

• Herring RA, Shojaee-Moradie F, Stevenage M, Parsons I, Jackson N, Mendis J, Middleton B, Umpleby AM, Fielding BA, Davies M, Russell-Jones DL. The SGLT2 Inhibitor Dapagliflozin Increases the Oxidation of Ingested Fatty Acids to Ketones in Type 2 Diabetes. Diabetes Care. 2022 Jun 2;45(6):1408-1415. doi: 10.2337/dc21-2043.

  PMID: 35312749 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Sodium-Glucose Transporter 2 Inhibitors; dapagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Hypoglycemic Agents; Physiological Effects of Drugs

Study Officials

• Roselle Herring, MD PhD

  CEDAR, Royal Surrey County Hospital

  PRINCIPAL INVESTIGATOR

• Mellanie Davis, MD PhD

  University of Leicester

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Matching placebo for Dapagliflozin 10 mg. Dosage form and strength: Green, plain, diamond shaped, and film coated tablet
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study is a randomised double blind placebo control cross over trial. with 4-weeks washout period.

Study Record Dates

• First Submitted: January 2, 2020
• First Posted: January 6, 2020
• Study Start: September 20, 2018
• Primary Completion: January 8, 2020
• Study Completion: January 8, 2020
• Last Updated: April 27, 2021

Record last verified: 2021-04

Locations

GB (1)