Dapagliflozin in Type 1 Diabetes

NCT02211742 | Completed Phase 4 DMC

• 1 other identifier: CUI_001
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Dapagliflozin is a highly selective, reversible and potent inhibitor of the sodium-glucose-linked Transporter 2 (SGLT2), which was successfully investigated for its use as a treatment option in type 2 diabetes mellitus. The effect of dapagliflozin is an increased glucosuria, and it was shown that mean blood glucose concentrations and postprandial glucose excursion in special were significantly reduced in type 2 diabetic patients. Due to its mechanism-of action it seems likely that also type 1 diabetic patients will benefit from dapagliflozin. The present study is focused on the effects of dapagliflozin on fasting glucose homeostasis and postprandial glucose excursion in male type 1diabetic patients. Participants will subsequently receive 10 milligrams of dapagliflozin and placebo for 3 days (equals 2 x 30mg per cross-over period) in a double-blind, randomised, cross-over design. The effects will be measured via euglycemic hyperinsulinemic clamp studies (fasting glucose homeostasis) and euglycemic oral glucose tolerance clamp tests (postprandial glucose excursions).

Conditions

Fasting Glucose; Glucose Excursion; Glycemic Control

Keywords

dapagliflozin; fasting glucose; postprandial glucose excursion; euglycemic hyperinsulinemic clamp; euglycemic oral glucose tolerance test

Outcome Measures

Primary Outcomes (2)

• fasting glucose homeostasis

  During hyperinsulinemic, euglycemic clamp studies, fasting glucose homeostasis will be determined for both, dapagliflozin and placebo.

  study visit, immediatly

• postprandial glucose homeostasis

  During euglycemic oral glucose tolerance clamp tests, postprandial glucose excursion will be determined and compared between dapagliflozin and placebo.

  study visit, immediatly

Study Arms (2)

dapagliflozin

ACTIVE COMPARATOR

10mg dapagliflozin per 24h for 3 days per cross-over phase (equals 2 x 30mg)

Drug: Dapagliflozin

placebo sugar pills

PLACEBO COMPARATOR

placebo tablet, 1 per 24h for 3 days in total per cross-over phase (equals 2 x 3 tablets)

Drug: Dapagliflozin

Interventions

Dapagliflozin DRUG

euglycemic hyperinsulinemic clamp tests and euglycemic oral glucose tolerance clamp tests after the short-term (i.e.: 3 days, equals 10mg / 24h) intake of dapagliflozin

dapagliflozin; placebo sugar pills

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Type 1 diabetes mellitus (duration of disease at least 5 years)
• C-peptide concentration \< 0.2µg/l
• male sex
• aged 18 to 60 years
• Body Mass Index 20 - 25 kg/m2
• no measurable, clinically relevant ketonuria

You may not qualify if:

• insufficient venous status on both forearms
• renal and/or hepatic insufficiency (including microalbuminuria and/or albumin/creatinin-ratio)
• history of cancer
• alcohol- and/or drug abuse, nicotine consumption \> 5 cigarettes / 24h
• brittle-diabetes
• history of severe hypoglycemia, defined as the need for foreign assistance independent of actual blood glucose concentration measured
• history or evidence of any other clinically significant disorder, condition or disease other than those outlined above that, in the opinion of the investigator may compromise the ability of the participant to give written informed consent, would pose a risk to subject safety, or interfere with the study evaluation, procedures or completion.

Sponsors & Collaborators

• Medical University Innsbruck: lead
• Medical University of Graz: collaborator
• University of Bern: collaborator

Study Sites (1)

Medical University Innsbruck, Department of Internal Medicine I

Innsbruck, Tyrol, 6020, Austria

Location

Related Publications (4)

• DeFronzo RA, Hompesch M, Kasichayanula S, Liu X, Hong Y, Pfister M, Morrow LA, Leslie BR, Boulton DW, Ching A, LaCreta FP, Griffen SC. Characterization of renal glucose reabsorption in response to dapagliflozin in healthy subjects and subjects with type 2 diabetes. Diabetes Care. 2013 Oct;36(10):3169-76. doi: 10.2337/dc13-0387. Epub 2013 Jun 4.

  PMID: 23735727 BACKGROUND

• Abdul-Ghani MA, DeFronzo RA. Dapagliflozin for the treatment of type 2 diabetes. Expert Opin Pharmacother. 2013 Aug;14(12):1695-703. doi: 10.1517/14656566.2013.812632. Epub 2013 Jun 26.

  PMID: 23800130 BACKGROUND

• Mather A, Pollock C. Glucose handling by the kidney. Kidney Int Suppl. 2011 Mar;(120):S1-6. doi: 10.1038/ki.2010.509.

  PMID: 21358696 BACKGROUND

• Plosker GL. Dapagliflozin: a review of its use in type 2 diabetes mellitus. Drugs. 2012 Dec 3;72(17):2289-312. doi: 10.2165/11209910-000000000-00000.

  PMID: 23170914 BACKGROUND

MeSH Terms

Interventions

dapagliflozin

Study Officials

• Markus Laimer, PD MD

  Medical University Innsbruck, Department of Internal Medicine I

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PD MD

Study Record Dates

• First Submitted: August 6, 2014
• First Posted: August 7, 2014
• Study Start: August 1, 2014
• Primary Completion: July 29, 2016
• Study Completion: February 8, 2017
• Last Updated: March 16, 2023

Record last verified: 2023-03

Locations

AU (1)