Effect of Dapagliflozin on IAH in T1DM

NCT ID: NCT03556033

Last Updated: 2020-03-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-23
• Study Completion Date: 2019-12-20

Brief Summary

Approximately 25% of patients with type 1 diabetes have lost the capacity to timely detect hypoglycaemia, a condition referred to as impaired awareness of hypoglycaemia (IAH) that causes a six-fold higher risk of severe, potentially hazardous, hypoglycaemia. IAH is usually the end-result of a process of habituation to recurrent hypoglycaemia that is potentially reversible. Treatment with sodium glucose cotransporter (SGLT)-2 inhibitors (SGLT-2i) in addition to insulin therapy may decrease the incidence of hypoglycaemia in patients with type 1 diabetes. This study will test the hypothesis that treatment with the SGLT-2 inhibitor, dapagliflozin, added to basal-bolus insulin therapy will improve awareness of hypoglycaemia in patients with type 1 diabetes and IAH. In a randomized doubleblind placebo-controlled cross-over trial, patients will be treated for 8 weeks with dapagliflozin (or placebo), after which hypoglycemic symptoms and counterregulatory hormone responses will be examined during a hyperinsulinemic hypoglycemic glucose clamp study.

Conditions

Diabetes Mellitus, Type 1; Hypoglycemia; Hypoglycemia Unawareness

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Dapagliflozin

Dapagliflozin 10 mg capsule once daily for 8 weeks

Group Type: ACTIVE_COMPARATOR

Dapagliflozin

Intervention Type: DRUG

8 weeks treatment with dapagliflozin on top of insulin treatment

Placebo oral capsule

Placebo matched to dapagliflozin 10 mg capsule once daily for 8 weeks

Group Type: PLACEBO_COMPARATOR

Placebo oral capsule

Intervention Type: DRUG

8 weeks treatment with placebo capsules on top of insulin treatment

Interventions

Dapagliflozin

8 weeks treatment with dapagliflozin on top of insulin treatment

Intervention Type: DRUG

Placebo oral capsule

8 weeks treatment with placebo capsules on top of insulin treatment

Intervention Type: DRUG

Other Intervention Names

Forxiga

Eligibility Criteria

Inclusion Criteria

• Type 1 diabetes, disease duration >1 year
• Age >18 years, <75 years
• BMI 19-40 kg/m^2
• Insulin treatment according to basal-bolus insulin regimen (injections or insulin pump)
• Impaired awareness of hypoglycemia as assessed by a score of 3 or more on the modified Dutch translation of the Clarke questionnaire
• Glycated haemoglobin (HbA1c) ≥42 mmol/mol (6%) and ≤75 mmol/mol (9.0%)
• Ability to provide informed consent

Exclusion Criteria

• Treatment with SGLT-2 inhibitors
• Known intolerance to SGLT-2 inhibitors
• Treatment with loop diuretics or other anti-hypertensive agents
• Treatment with glucose-modifying (other than insulin) or immune-modifying agents (e.g. prednisolon)
• Treatment with pioglitazone
• Use of statins
• A history of cardiovascular disease (e.g. myocardial infarction, stroke, heart failure) or hypotension
• A history of galactose-intolerance, lactase deficiency, glucose-galactose malabsorption
• History of diabetic ketoacidosis requiring medical intervention within 1 month before screening
• Admission to the hospital for hyperglycemia or hypoglycemia within 1 month before screening
• Frequent episodes of severe hypoglycemia within 1 month before screening
• Laser coagulation for proliferative retinopathy (past 6 months)
• Proliferative retinopathy
• Diabetic nephropathy as reflected by an albumin-creatinin ratio ˃ 30 mmol/mg or an estimated glomerular filtration rate (by MDRD) ˂60ml/min/1.73m2
• History of pancreatitis (acute or chronic) or pancreatic cancer
• Use of premixed insulin or of long-acting insulin alone
• Total daily insulin dose requirements <20 units unless on pump treatment
• Pregnancy or unwillingness to undertake measures for birth control

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Radboud university medical center

Nijmegen, , Netherlands

Countries

Netherlands

Other Identifiers

T1DM_IAH_dapa

Identifier Type: -

Identifier Source: org_study_id