Effect of Dapagliflozin on IAH in T1DM

NCT03556033 | Completed Phase 2

• 1 other identifier: T1DM_IAH_dapa
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Symptom score in response to insulin-induced hypoglycaemia

  Symptom scores (autonomic, neuroglycopenic and general) measured during hyperinsulinemic hypoglycaemic glucose clamps. This questionnaire consists of 18 symptoms, which can be scored between 0 (none) to 6 (severe). Total scores range between 0 and 108, the higher the score, the more symptoms patients have during and after hypoglycemia.

  45 minutes

Secondary Outcomes (10)

• Counterregulatory hormone responses to insulin-induced hypoglycaemia

  45 minutes

• Time until glycaemic recovery from hypoglycaemia

  45 minutes

• Maximal glucose excursion post-hypoglycaemia

  45 minutes

• Time until glucose peak post-hypoglycaemia

  45 minutes

• Area under the glucose concentration curve post-hypoglycaemia

  45 minutes

Other Outcomes (1)

• Inflammatory/atherogenic phenotype of circulating monocytes from the participating patients

  45 minutes

Study Arms (2)

Dapagliflozin

ACTIVE COMPARATOR

Dapagliflozin 10 mg capsule once daily for 8 weeks

Drug: Dapagliflozin

Placebo oral capsule

PLACEBO COMPARATOR

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

Drug: Placebo oral capsule

Interventions

Dapagliflozin DRUG

8 weeks treatment with dapagliflozin on top of insulin treatment

Also known as: Forxiga

Dapagliflozin

Placebo oral capsule DRUG

8 weeks treatment with placebo capsules on top of insulin treatment

Placebo oral capsule

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

Radboud university medical center

Nijmegen, 6500HB, Netherlands

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Hypoglycemia

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2018
• First Posted: June 14, 2018
• Study Start: November 23, 2018
• Primary Completion: December 20, 2019
• Study Completion: December 20, 2019
• Last Updated: March 23, 2020

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)