Clinical trial NCT02211742: Dapagliflozin in Type 1 Diabetes
Official title: Short-term Effects of Dapagliflozin on Fasting and Postprandial Glucose Homeostasis in Male Type 1 Diabetes Patients.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Fasting Glucose
Glucose Excursion
Glycemic Control
Keywords: dapagliflozin
fasting glucose
postprandial glucose excursion
euglycemic hyperinsulinemic clamp
euglycemic oral glucose tolerance test
Lead sponsor: Medical University Innsbruck
Sponsor class: OTHER
Collaborators: name: Medical University of Graz
name: University of Bern
First posted: 2014-08-07
Enrollment: 12
Sex: MALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* insufficient venous status on both forearms
* renal and/or hepatic insufficiency (including microalbuminuria and/or albumin/creatinin-ratio)
* history of cancer
* intake of medication and/or substances capable to influence insulin sensitivity within the last 3 months prior to study inclusion
* 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.

Primary outcomes:
measure: fasting glucose homeostasis
timeFrame: study visit, immediatly
measure: postprandial glucose homeostasis
timeFrame: study visit, immediatly
Secondary outcomes:
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Medical University Innsbruck, Department of Internal Medicine I
state: Tirol
Study officials:
affiliation: Medical University Innsbruck, Department of Internal Medicine I
name: Markus Laimer, PD MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: Mather A, Pollock C. Glucose handling by the kidney. Kidney Int Suppl. 2011 Mar;(120):S1-6. doi: 10.1038/ki.2010.509.
citation: 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.